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      string: "<?xml version=\"1.0\" ?>\n<!DOCTYPE pmc-articleset PUBLIC \"-//NLM//DTD
        ARTICLE SET 2.0//EN\" \"https://dtd.nlm.nih.gov/ncbi/pmc/articleset/nlm-articleset-2.0.dtd\">\n<pmc-articleset><article
        xmlns:xlink=\"http://www.w3.org/1999/xlink\" xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"
        article-type=\"review-article\">\n  <?properties open_access?>\n  <front>\n
        \   <journal-meta>\n      <journal-id journal-id-type=\"nlm-ta\">Front Psychiatry</journal-id>\n
        \     <journal-id journal-id-type=\"publisher-id\">Front. Psychiatry</journal-id>\n
        \     <journal-title-group>\n        <journal-title>Frontiers in Psychiatry</journal-title>\n
        \     </journal-title-group>\n      <issn pub-type=\"epub\">1664-0640</issn>\n
        \     <publisher>\n        <publisher-name>Frontiers Research Foundation</publisher-name>\n
        \     </publisher>\n    </journal-meta>\n    <article-meta>\n      <article-id
        pub-id-type=\"pmid\">22416237</article-id>\n      <article-id pub-id-type=\"pmc\">3299399</article-id>\n
        \     <article-id pub-id-type=\"doi\">10.3389/fpsyt.2012.00018</article-id>\n
        \     <article-categories>\n        <subj-group subj-group-type=\"heading\">\n
        \         <subject>Psychiatry</subject>\n          <subj-group>\n            <subject>Review
        Article</subject>\n          </subj-group>\n        </subj-group>\n      </article-categories>\n
        \     <title-group>\n        <article-title>The Effects of Psychosis Risk
        Variants on Brain Connectivity: A Review</article-title>\n      </title-group>\n
        \     <contrib-group>\n        <contrib contrib-type=\"author\">\n          <name>\n
        \           <surname>Mothersill</surname>\n            <given-names>Omar</given-names>\n
        \         </name>\n          <xref ref-type=\"aff\" rid=\"aff1\">\n            <sup>1</sup>\n
        \         </xref>\n          <xref ref-type=\"aff\" rid=\"aff2\">\n            <sup>2</sup>\n
        \         </xref>\n          <xref ref-type=\"author-notes\" rid=\"fn002\">\n
        \           <sup>&#x2020;</sup>\n          </xref>\n        </contrib>\n        <contrib
        contrib-type=\"author\">\n          <name>\n            <surname>Kelly</surname>\n
        \           <given-names>Sinead</given-names>\n          </name>\n          <xref
        ref-type=\"aff\" rid=\"aff1\">\n            <sup>1</sup>\n          </xref>\n
        \         <xref ref-type=\"aff\" rid=\"aff2\">\n            <sup>2</sup>\n
        \         </xref>\n          <xref ref-type=\"author-notes\" rid=\"fn002\">\n
        \           <sup>&#x2020;</sup>\n          </xref>\n        </contrib>\n        <contrib
        contrib-type=\"author\">\n          <name>\n            <surname>Rose</surname>\n
        \           <given-names>Emma Jane</given-names>\n          </name>\n          <xref
        ref-type=\"aff\" rid=\"aff1\">\n            <sup>1</sup>\n          </xref>\n
        \         <xref ref-type=\"aff\" rid=\"aff2\">\n            <sup>2</sup>\n
        \         </xref>\n        </contrib>\n        <contrib contrib-type=\"author\">\n
        \         <name>\n            <surname>Donohoe</surname>\n            <given-names>Gary</given-names>\n
        \         </name>\n          <xref ref-type=\"aff\" rid=\"aff1\">\n            <sup>1</sup>\n
        \         </xref>\n          <xref ref-type=\"aff\" rid=\"aff2\">\n            <sup>2</sup>\n
        \         </xref>\n          <xref ref-type=\"author-notes\" rid=\"fn001\">*</xref>\n
        \       </contrib>\n      </contrib-group>\n      <aff id=\"aff1\">\n        <sup>1</sup>\n
        \       <institution>Neuropsychiatric Genetics Group, Department of Psychiatry,
        Trinity College Dublin</institution>\n        <country>Dublin, Ireland</country>\n
        \     </aff>\n      <aff id=\"aff2\">\n        <sup>2</sup>\n        <institution>Trinity
        College Institute for Neuroscience, Trinity College Dublin</institution>\n
        \       <country>Dublin, Ireland</country>\n      </aff>\n      <author-notes>\n
        \       <fn fn-type=\"edited-by\">\n          <p>Edited by: Daniela Tropea,
        Trinity College Dublin, Ireland</p>\n        </fn>\n        <fn fn-type=\"edited-by\">\n
        \         <p>Reviewed by: Mikhail Pletnikov, Johns Hopkins University, USA;
        Andrew M. McIntosh, The University of Edinburgh, UK</p>\n        </fn>\n        <corresp
        id=\"fn001\">*Correspondence: Gary Donohoe, Associate Professor of Clinical
        Psychology and Neuropsychology, Neuropsychiatric Genetics Group, Department
        of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences,
        St. James&#x2019; Hospital, Dublin 8, Ireland. e-mail: <email>donoghug@tcd.ie</email></corresp>\n
        \       <fn fn-type=\"other\" id=\"fn002\">\n          <p><sup>&#x2020;</sup>Omar
        Mothersill and Sinead Kelly have contributed equally to this work.</p>\n        </fn>\n
        \       <fn fn-type=\"other\" id=\"fn003\">\n          <p>This article was
        submitted to Frontiers in Molecular Psychiatry, a specialty of Frontiers in
        Psychiatry.</p>\n        </fn>\n      </author-notes>\n      <pub-date pub-type=\"epub\">\n
        \       <day>09</day>\n        <month>3</month>\n        <year>2012</year>\n
        \     </pub-date>\n      <pub-date pub-type=\"collection\">\n        <year>2012</year>\n
        \     </pub-date>\n      <volume>3</volume>\n      <elocation-id>18</elocation-id>\n
        \     <history>\n        <date date-type=\"received\">\n          <day>02</day>\n
        \         <month>12</month>\n          <year>2011</year>\n        </date>\n
        \       <date date-type=\"accepted\">\n          <day>22</day>\n          <month>2</month>\n
        \         <year>2012</year>\n        </date>\n      </history>\n      <permissions>\n
        \       <copyright-statement>Copyright &#xA9; 2012 Mothersill, Kelly, Rose
        and Donohoe.</copyright-statement>\n        <copyright-year>2012</copyright-year>\n
        \       <license license-type=\"open-access\" xlink:href=\"http://www.frontiersin.org/licenseagreement\">\n
        \         <license-p>This is an open-access article distributed under the
        terms of the <uri xlink:type=\"simple\" xlink:href=\"http://creativecommons.org/licenses/by-nc/3.0/\">Creative
        Commons Attribution Non Commercial License</uri>, which permits non-commercial
        use, distribution, and reproduction in other forums, provided the original
        authors and source are credited.</license-p>\n        </license>\n      </permissions>\n
        \     <abstract>\n        <p>In light of observed changes in connectivity
        in schizophrenia and the highly heritable nature of the disease, neural connectivity
        may serve as an important intermediate phenotype for schizophrenia. However,
        how individual variants confer altered connectivity and which measure of brain
        connectivity is more proximal to the underlying genetic architecture (i.e.,
        functional or structural) has not been well delineated. In this review we
        consider these issues and the relative sensitivity of imaging methodologies
        to schizophrenia-related changes in connectivity. We searched PubMed for studies
        considering schizophrenia risk genes AND functional or structural connectivity.
        Where data was available, summary statistics were used to determine an estimate
        of effect size (i.e., Cohen&#x2019;s <italic>d</italic>). A random-effects
        meta-analysis was used to consider (1) the largest effect and (2) all significant
        effects between functional and structural studies. Schizophrenia risk variants
        involved in neurotransmission, neurodevelopment and myelin function were found
        to be associated with altered neural connectivity. On average, schizophrenia
        risk genes had a large effect on functional (mean <italic>d&#x2009;</italic>=&#x2009;0.76)
        and structural connectivity (mean <italic>d&#x2009;</italic>=&#x2009;1.04).
        The examination of the largest effect size indicated that the outcomes of
        functional and structural studies were comparable (<italic>Q</italic>&#x2009;=&#x2009;2.17,
        <italic>p</italic>&#x2009;&gt;&#x2009;0.05). Conversely, consideration of
        effect size estimates for <italic>all</italic> significant effects suggest
        that reported effect sizes in structural connectivity studies were more variable
        than in functional connectivity studies, and that there was a significant
        lack of homogeneity across the modalities (<italic>Q</italic>&#x2009;=&#x2009;6.928,
        <italic>p</italic>&#x2009;=&#x2009;0.008). Given the more variable profile
        of effect sizes associated with structural connectivity, these data may suggest
        that structural imaging methods are more sensitive to a wider range of effects,
        as opposed to functional studies which may only be able to determine large
        effects. These conclusions are limited by methodological considerations, and
        require further investigation involving larger samples, multiple genes, and
        novel analysis techniques for confirmation.</p>\n      </abstract>\n      <kwd-group>\n
        \       <kwd>schizophrenia</kwd>\n        <kwd>functional connectivity</kwd>\n
        \       <kwd>structural connectivity</kwd>\n        <kwd>genotype</kwd>\n
        \       <kwd>effect size</kwd>\n      </kwd-group>\n      <counts>\n        <fig-count
        count=\"2\"/>\n        <table-count count=\"3\"/>\n        <equation-count
        count=\"0\"/>\n        <ref-count count=\"76\"/>\n        <page-count count=\"12\"/>\n
        \       <word-count count=\"10126\"/>\n      </counts>\n    </article-meta>\n
        \ </front>\n  <body>\n    <sec>\n      <title>Introduction</title>\n      <sec>\n
        \       <title>Examining the function of schizophrenia (SZ) risk variants</title>\n
        \       <p>Schizophrenia is a complex genetic disorder affecting roughly 1%
        of the world&#x2019;s population (see Lewis and Lieberman, <xref ref-type=\"bibr\"
        rid=\"B30\">2000</xref> for a review). It is characterized by hallucinations
        and delusions, reduced emotion and cognitive impairment, and imposes a heavy
        cost on society (for example, the total cost of psychotic disorders in Europe
        in 2010 was recently calculated as &#x20AC;93.9 billion; Gustavsson et al.,
        <xref ref-type=\"bibr\" rid=\"B18\">2011</xref>). While there is no consensus
        about its exact causes, the heritability of SZ is estimated to be about 80%
        (Sullivan et al., <xref ref-type=\"bibr\" rid=\"B64\">2003</xref>). Genome-wide
        association (GWAS) and copy number variation studies have identified several
        common and rare gene variants associated with the disorder (O&#x2019;Donovan
        et al., <xref ref-type=\"bibr\" rid=\"B45\">2008</xref>). Understanding the
        function of these variants could, therefore, lead to a greater understanding
        of disease pathogenesis, which could direct new treatments.</p>\n        <p>Schizophrenia
        patients present with variable symptom profiles and distinct disease trajectories.
        This heterogeneity may be in part due to the complex genetics of SZ, which
        in turn poses significant problems for understanding the mechanisms by which
        genetic variants confer risk for this disease. In an attempt to address this
        complexity, researchers have focused on so-called &#x201C;intermediate phenotypes,&#x201D;
        which are measurable variations that occur on the pathway between genes and
        disease, and as such may be closer to the underlying genetic architecture
        than clinical symptoms (see Gottesman and Gould, <xref ref-type=\"bibr\" rid=\"B17\">2003</xref>
        for a review). Possible intermediate phenotypes for SZ include changes in
        brain chemistry, structure, function (Braff et al., <xref ref-type=\"bibr\"
        rid=\"B1\">2007</xref>) and connectivity (Meyer-Lindenberg, <xref ref-type=\"bibr\"
        rid=\"B35\">2009</xref>).</p>\n        <p>While changes in functional and
        structural connectivity may be a critical aspect of the SZ disease profile,
        there has been little systematic evaluation of the relative sensitivity of
        these different indices to genetic risk for SZ. In this meta-analysis we outline
        empirical investigations that have utilized functional magnetic resonance
        imaging (fMRI) or diffusion tensor imaging (DTI) to investigate the effects
        of SZ risk variants on functional and structural brain connectivity. We also
        consider the relative magnitude of these effects, in order to determine the
        extent of the genetic impact on brain connectivity.</p>\n      </sec>\n      <sec>\n
        \       <title>Altered functional connectivity in SZ</title>\n        <p>In
        the early 20th century, German neurologist Carl Wernicke proposed that SZ
        arises from altered neural connectivity (or dysconnectivity) rather than from
        abnormalities in specific parts of the brain (see Stephan et al., <xref ref-type=\"bibr\"
        rid=\"B62\">2009</xref> for a review). One hundred years later, advances in
        neuroimaging technology have enabled scientists to empirically consider dysconnectivity
        as a key component of SZ pathogenesis.</p>\n        <p>Two or more brain regions
        are said to be functionally connected if they show a correlation of activity
        over time (Friston et al., <xref ref-type=\"bibr\" rid=\"B15\">1993</xref>).
        The hypothesis that functional connectivity is altered in SZ is supported
        by positron emission tomography (PET; e.g., Friston and Frith, <xref ref-type=\"bibr\"
        rid=\"B14\">1995</xref>; Meyer-Lindenberg et al., <xref ref-type=\"bibr\"
        rid=\"B37\">2001</xref>, <xref ref-type=\"bibr\" rid=\"B39\">2005</xref>)
        and fMRI studies (Lawrie et al., <xref ref-type=\"bibr\" rid=\"B29\">2002</xref>),
        which reveal abnormal prefronto-temporal connectivity in SZ patients while
        they perform cognitive tasks. Electroencephalogram (EEG) research also demonstrates
        abnormal functional connectivity patterns in patients with SZ (Breakspear
        et al., <xref ref-type=\"bibr\" rid=\"B2\">2003</xref>), and one genetic mouse
        model of SZ reveals decreased hippocampal-prefrontal connectivity during a
        T-maze task (Sigurdsson et al., <xref ref-type=\"bibr\" rid=\"B59\">2010</xref>).</p>\n
        \       <p>Support for the role of functional connectivity as an intermediate
        phenotype for psychiatric disorders includes a fMRI study by Pezawas et al.,
        <xref ref-type=\"bibr\" rid=\"B50\">2005</xref>). These authors examined the
        effects of a 5-HTTLPRpolymorphism that is associated with anxiety and depression,
        on functional connectivity between the amygdala and cingulate cortex. It was
        reported that variant-associated changes in connectivity predicted almost
        30% of the variance in the behavioral effects of this polymorphism. Behavioral
        variability was also in fact better predicted by changes in connectivity than
        changes in regional brain activation.</p>\n        <p>Understanding the underlying
        biological causes of altered functional connectivity has the potential to
        lead to a better understanding of SZ pathogenesis, but so far the etiology
        of functional dysconnectivity remains unclear. However, different mechanisms
        have been proposed, which we will discuss in the following sections.</p>\n
        \     </sec>\n      <sec>\n        <title>The &#x201C;disconnection&#x201D;
        hypothesis of SZ</title>\n        <p>The &#x201C;disconnection&#x201D; hypothesis
        was first proposed by Karl Friston and colleagues in the 1990s (Friston, <xref
        ref-type=\"bibr\" rid=\"B12\">1998</xref>). This hypothesis postulates that
        SZ is primarily caused by abnormal <italic>N</italic>-methyl-<sc>d</sc>-aspartate
        (NMDA)-receptor mediated synaptic plasticity, which in turn, is caused by
        dysregulation of these receptors by neurotransmitters such as dopamine. Support
        for the role of the NMDA receptor in SZ comes from several studies. Firstly,
        drugs that block the NMDA-receptor, such as ketamine and phencyclidine, can
        induce psychotic symptoms in healthy controls (see Javitt, <xref ref-type=\"bibr\"
        rid=\"B21\">2010</xref> for a review). Similarly, ketamine administration
        induces sensory processing deficits in controls similar to deficits seen in
        patients, suggesting a role for NMDA receptors in these deficits (Umbricht
        et al., <xref ref-type=\"bibr\" rid=\"B70\">2000</xref>). Activity of midbrain
        dopaminergic neurons is partially regulated by glutamatergic projections from
        the prefrontal cortex (PFC), acting via NMDA receptors, and NMDA receptor-blockade
        enhances amphetamine-induced increases in striatal dopamine in controls, similar
        to increases seen in SZ patients (Kegeles et al., <xref ref-type=\"bibr\"
        rid=\"B24\">2000</xref>). Finally, genetic variants that play a role in NMDA-signaling
        have been associated with increased SZ risk in candidate gene studies [e.g.,
        <italic>G72</italic>,<italic>GRM3</italic> and <italic>RGS4</italic>; see
        Harrison and Weinberger (<xref ref-type=\"bibr\" rid=\"B20\">2005</xref>)
        for a review].</p>\n      </sec>\n      <sec>\n        <title>Functional connectivity
        MRI analysis techniques</title>\n        <p>Functional connectivity can be
        measured with a variety of tools (e.g., PET, EEG), but this review will focus
        on papers using fMRI to measure the phenotype in healthy controls and patients
        with SZ. Using the blood oxygen level dependent (BOLD) response as an indirect
        measure of neuronal activity (Ogawa et al., <xref ref-type=\"bibr\" rid=\"B46\">1990</xref>),
        there are a range of approaches to analysis. This review will focus on <italic>seeded
        connectivity</italic> and <italic>psychophysiological interaction</italic>
        (PPI).</p>\n        <p>A seeded connectivity analysis begins with the selection
        of a seed region, which can be a voxel, or cluster of voxels in the fMRI time-series
        (Nallasamy and Tsao, <xref ref-type=\"bibr\" rid=\"B42\">2011</xref>). The
        mean time-course for the seed region is then correlated with all other voxels
        in the brain. Voxels that pass a certain threshold are considered to be functionally
        connected with the seed region, resulting in a functional connectivity map.
        While the PPI approach also measures the co-variation of the BOLD signal in
        voxels across the brain (Friston et al., <xref ref-type=\"bibr\" rid=\"B13\">1997</xref>),
        it also measures changes in the interactions between brain regions in response
        to different psychological tasks.</p>\n      </sec>\n      <sec>\n        <title>Structural
        connectivity and SZ</title>\n        <p>White matter (WM) contains myelinated
        nerve cells that connect various gray matter (GM) areas of the brain to each
        other, and carry nerve impulses between neurons. Compromised WM integrity
        is evident in SZ (Kubicki et al., <xref ref-type=\"bibr\" rid=\"B28\">2007</xref>;
        Ellison-Wright and Bullmore, <xref ref-type=\"bibr\" rid=\"B8\">2009</xref>).
        Moreover, WM abnormalities are apparent in individuals at high risk of SZ
        and also in patients during the early stages of illness, suggesting that these
        abnormalities may be a stable characteristic of the disease (Witthaus et al.,
        <xref ref-type=\"bibr\" rid=\"B75\">2008</xref>; Perez-Iglesias et al., <xref
        ref-type=\"bibr\" rid=\"B49\">2010</xref>). There are two key postulations
        regarding the nature of WM deficits in SZ: The &#x201C;<italic>global theory</italic>&#x201D;
        and the &#x201C;<italic>macro-circuit theory</italic>.&#x201D; The global
        theory of WM disruption in SZ suggests that WM is compromised uniformly throughout
        the brain, whereas the macro-circuit theory proposes that specific WM tracts
        are compromised, which may be a cause <italic>or</italic> consequence of abnormalities
        in the gray matter regions these tracts connect (Buchsbaum et al., <xref ref-type=\"bibr\"
        rid=\"B3\">2006</xref>; Konrad and Winterer, <xref ref-type=\"bibr\" rid=\"B27\">2008</xref>).</p>\n
        \       <sec>\n          <title>Diffusion tensor imaging</title>\n          <p>Diffusion
        tensor imaging is a method used to measure the diffusion of water molecules
        in brain WM. Healthy brain WM has a complex axonal structure and, therefore,
        water diffusion will be restricted along the direction of the axons. This
        is known as <italic>anisotropic</italic> diffusion. However, if brain WM is
        compromised water diffusion can become less restricted (i.e., <italic>isotropic</italic>).
        A common measure derived from DTI to describe the degree of anisotropy during
        diffusion is <italic>fractional anisotropy</italic> (FA). However, other measures
        of diffusion such as radial and axial diffusivity can also be obtained. Based
        on the voxel-wise information provided by DTI, fiber tracking algorithms can
        be implemented in regions of interest to reconstruct the underlying three-dimensional
        WM pathways. While caution must be exercised when interpreting measures of
        anisotropy (Jones, <xref ref-type=\"bibr\" rid=\"B22\">2008</xref>, <xref
        ref-type=\"bibr\" rid=\"B23\">2010</xref>; Tournier et al., <xref ref-type=\"bibr\"
        rid=\"B69\">2011</xref>), such measures are thought to index structural integrity
        of WM tracts and, thus, may be reasonably considered to be implicit indices
        of brain connectivity.</p>\n        </sec>\n        <sec>\n          <title>WM
        integrity and SZ: evidence from DTI investigations</title>\n          <p>A
        review by Kubicki et al. (<xref ref-type=\"bibr\" rid=\"B28\">2007</xref>)
        noted that the most frequent positive findings of DTI studies in SZ were decreased
        FA within the prefrontal and temporal lobes, as well as abnormalities within
        the fiber bundles connecting these regions. WM tracts within these regions
        that were found to be affected included: (a) the uncinate fasciculus that
        connects parts of the limbic system with areas in the frontal cortex; (b)
        the cingulum bundle; and (c) the arcuate fasciculus that connects part of
        the temporo-parietal junction with the frontal cortex and is thought to be
        part of the superior longitudinal fasciculus. Ellison-Wright and Bullmore
        (<xref ref-type=\"bibr\" rid=\"B8\">2009</xref>) conducted a meta-analysis
        of 15 DTI studies, which included a total of 407 patients with SZ and 383
        comparison subjects. Results identified two regions of FA decreases in SZ
        subjects in comparison to controls. The first region was in the left frontal
        deep WM, which is traversed by WM tracts interconnecting the frontal lobe,
        thalamus and cingulate gyrus. The tracts include: (a) anterior thalamic radiation
        (ATR); (b) corticobulbar tracts; (c) inter-hemispheric fibers running through
        the genu of the corpus callosum; (d) the inferior fronto-occipital fasciculus;
        (e) the cingulum bundle. The second region was in the left temporal deep WM
        that is traversed by WM tracts interconnecting the frontal lobe, insula, hippocampus&#x2013;amygdala,
        temporal and occipital lobes. These tracts include: (a) inter-hemispheric
        fibers running through the splenium of the corpus callosum; (b) the inferior
        fronto-occipital fasciculus; (c) the inferior longitudinal fasciculus; (d)
        the fornix/striaterminalis. These two reviews of the current DTI/SZ literature
        suggest that specific networks of WM are disrupted in SZ providing support
        for the macro-circuit theory of WM disruption in the disease.</p>\n        </sec>\n
        \       <sec>\n          <title>Pathophysiological mechanisms of compromised
        WM</title>\n          <p>As the integrity of axons is dependent on myelination
        and factors influencing myelination, it is possible that myelin and oligodendroglia
        function also plays a role in the pathophysiology of SZ (Davis et al., <xref
        ref-type=\"bibr\" rid=\"B6\">2003</xref>). Since myelination also impacts
        synaptic plasticity, oligodendrocyte abnormality and subsequent myelin dysfunction
        may contribute to the development of SZ by altering synaptic function and
        information processing (Fields, <xref ref-type=\"bibr\" rid=\"B11\">2008</xref>).
        Conduction velocity along axons is also thought to be essential for learning
        processes (Fields, <xref ref-type=\"bibr\" rid=\"B11\">2008</xref>) and disruption
        of this has the potential to lead to the range of cognitive impairments observed
        in SZ (Tanaka et al., <xref ref-type=\"bibr\" rid=\"B66\">2009</xref>). Furthermore,
        oligodendrocyte and myelin dysfunction also impacts neuronal activity that
        is relevant to SZ, such as glutamate and dopamine signaling. Evidence from
        psychotic episodes of multiple sclerosis (MS) patients and experimentally
        induced demyelination suggests that altered myelin function leads to altered
        dopamine signaling (Takahashi et al., <xref ref-type=\"bibr\" rid=\"B65\">2011</xref>).
        Similar analyses have also revealed increased levels of glutamate in brains
        of MS patients as well as increased expression of glutamate receptors on oligodendrocytes
        (Takahashi et al., <xref ref-type=\"bibr\" rid=\"B65\">2011</xref>). Glutamate
        transporters are also present on oligodendroglia and are thought to regulate
        glutamate concentrations to prevent glutamate-induced excitotoxicity (Pitt
        et al., <xref ref-type=\"bibr\" rid=\"B51\">2003</xref>). Over activation
        of oligodendroglial glutamate receptors is excitotoxic and can result in oligodendrocyte
        death (Davis et al., <xref ref-type=\"bibr\" rid=\"B6\">2003</xref>).</p>\n
        \         <p>Recently, attention has turned toward the consideration of genes
        that influence oligodendrocyte architecture and how these genes may also be
        associated with SZ risk. Hakak et al. (<xref ref-type=\"bibr\" rid=\"B19\">2001</xref>)
        examined the expression of 6500 genes derived from postmortem cortical tissue
        of SZ patients and controls. The expression levels of six myelin-related genes
        were significantly down regulated for SZ patients in comparison to control
        subjects. These genes included: myelin-associated glycoprotein (MAG), CNP,
        myelin and lymphocyte protein (MAL), gelosn (GSN), ErbB3, and transferring.
        Down regulation of these genes supports the view that oligodendrocytes, the
        cell type from which all these genes derive in the brain, contribute to the
        pathophysiology of SZ.</p>\n        </sec>\n      </sec>\n      <sec>\n        <title>Using
        imaging genetics to examine neural connectivity</title>\n        <p>Two previous
        meta-analyses have considered the magnitude of the impact of gene variants
        on brain function, each reporting large effect sizes. Munafo et al. (<xref
        ref-type=\"bibr\" rid=\"B41\">2008</xref>) examined the effect sizes of the
        5-HTTLPR polymorphism and amygdala activation, while Mier et al. (<xref ref-type=\"bibr\"
        rid=\"B40\">2010</xref>) examined the magnitude of effect of the catechol-<italic>O</italic>-methyltransferase
        (<italic>COMT</italic>) Val158Met polymorphism on brain function, reporting
        association between this variant and activation of the PFC. However, to our
        knowledge no studies have specifically considered the effect size of gene
        variants in studies of functional and structural connectivity, or compared
        effect sizes between these phenotypes. Consideration of the relative impact
        of these two measures of brain connectivity will help us to better delineate
        whether or not one phenotype is more proximal to the underlying genetics,
        and thus preferential as an intermediate phenotype for studies of SZ. This
        could not only aid our theoretical understanding of the SZ disease trajectory
        but may also have significant practical implications for future investigations.</p>\n
        \     </sec>\n    </sec>\n    <sec sec-type=\"methods\">\n      <title>Methods</title>\n
        \     <p>We searched for relevant papers based on the criteria of studies
        that included genes implicated in SZ risk <italic>and</italic> measures of
        either DTI or functional connectivity. PubMed (<uri xlink:type=\"simple\"
        xlink:href=\"http://www.ncbi.nlm.nih.gov/pubmed/\">http://www.ncbi.nlm.nih.gov/pubmed/</uri>)
        was used to search for relevant functional and structural connectivity papers
        published until June 2011. The following search terms were included in this
        search: [schizophrenia OR schiz*] AND [genetic or gene*] AND [MRI OR DTI]
        AND [connectivity] AND [structural OR functional]. This literature search
        was supplemented with a review of the references from each of the papers identified.
        In total 24 studies meeting these search criteria were retrieved, including
        12 DTI studies and 12 functional connectivity studies. Individual studies
        differed slightly in terms of MRI acquisition and analysis parameters (e.g.,
        voxel size, size of Gaussian function used for smoothing). However, all studies
        were included regardless of these differences, due to the small number of
        studies available. Where the data presented were insufficient for effect size
        calculations, a request for supplementary data was sent to the corresponding
        author. This led to data being available for 19 out of the 24 studies identified
        (10 DTI studies and 9 functional connectivity studies).</p>\n      <p>Effect
        size calculations were performed using two online effect size calculators
        <italic><uri xlink:type=\"simple\" xlink:href=\"http://www.uccs.edu/~faculty/lbecker/\">http://www.uccs.edu/&#x223C;faculty/lbecker/</uri></italic>
        and <italic><uri xlink:type=\"simple\" xlink:href=\"http://www.lyonsmorris.com/ma1/index.cfm\">www.lyonsmorris.com/ma1/index.cfm</uri></italic>
        Estimates of effect size were calculated based upon either descriptive data
        (i.e., mean, SD, and <italic>N</italic>), or statistical data (i.e., <italic>t,
        F</italic>). The purpose of this paper was to estimate differences in effect
        size rather than differences in direction of effect. That is we were interested
        in delineating the relative sensitivity of these two indices of brain connectivity
        to genetic variability, rather than accounting for the overall impact of a
        specific variant or group of variants. Therefore, direction of effect was
        not included in the analysis and all effect sizes were considered positive.</p>\n
        \     <p>A random effects meta-analyses considering the relative difference
        in the impact of SZ risk genes on functional and structural connectivity was
        carried out using the comprehensive meta analysis (CMA; software package v2;
        <uri xlink:type=\"simple\" xlink:href=\"http://www.meta-analysis.com\">www.meta-analysis.com</uri>).
        For the purposes of this analysis, Hedge&#x2019;s <italic>g</italic> and its
        associated variance were calculated for the outcome of each significant effect
        in each study. As with prior estimates of Cohen&#x2019;s d, g was calculated
        using a variety of input variables including descriptive and inferential statistics.
        In the first analysis, the largest effect for each study was chosen so to
        reflect the maximal sensitivity to gene effects within each investigation.
        In a secondary analysis, all of the effects for each significant result in
        each paper were taken into account. This strategy allowed us to account for
        both variability in the number and range of significant effects reported across
        methodologies.</p>\n    </sec>\n    <sec>\n      <title>Results</title>\n
        \     <p>Overall, 8 fMRI and 10 DTI studies were included in the meta-analysis.
        Summary information from all of these studies is presented in Tables <xref
        ref-type=\"table\" rid=\"T1\">1</xref> and <xref ref-type=\"table\" rid=\"T2\">2</xref>.</p>\n
        \     <table-wrap id=\"T1\" position=\"float\">\n        <label>Table 1</label>\n
        \       <caption>\n          <p><bold>Details of the functional connectivity
        studies included in this meta-analysis</bold>.</p>\n        </caption>\n        <table
        frame=\"hsides\" rules=\"groups\">\n          <thead>\n            <tr>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">First author
        and date</th>\n              <th align=\"left\" rowspan=\"1\" colspan=\"1\">Gene
        of interest</th>\n              <th align=\"left\" rowspan=\"1\" colspan=\"1\">Connectivity</th>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">Method</th>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">Statistic</th>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>n</italic>\n
        \             </th>\n              <th align=\"left\" rowspan=\"1\" colspan=\"1\">Cohen&#x2019;s
        <italic>d</italic></th>\n            </tr>\n          </thead>\n          <tbody>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Meyer-Lindenberg
        et al. (<xref ref-type=\"bibr\" rid=\"B38\">2007</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>PPP1R1B</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">L.
        PFC &#x2013; striatum, frequent haplotype carriers&#x2009;&gt;&#x2009;non-frequent
        haplotype carriers</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">4.41<sup>&#x2020;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">126</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.79</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">R. PFC &#x2013; striatum, frequent
        haplotype carriers&#x2009;&gt;&#x2009;non-frequent haplotype carriers</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.57<sup>&#x2020;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">126</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.82</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">L. PFC &#x2013; striatum, frequent
        haplotype carriers&#x2009;&gt;&#x2009;non-frequent haplotype carriers</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.31<sup>&#x2020;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">142</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.73</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Kempf
        et al. (<xref ref-type=\"bibr\" rid=\"B25\">2008</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>PRODH</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">dlPFC
        &#x2013; striatum, reference haplotype carriers&#x2009;&gt;&#x2009;protective
        haplotype carriers</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">3.91*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">103(108 total)</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.79</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">dlPFC &#x2013; striatum, risk haplotype
        carriers&#x2009;&gt;&#x2009;protective haplotype carriers</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.88*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">48(108 total)</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.87</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Di Giorgio et al. (<xref ref-type=\"bibr\"
        rid=\"B7\">2008</xref>)</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">\n                <italic>DISC1</italic>\n              </td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. hippocampus
        &#x2013; R. dlPFC, Ser/Ser&#x2009;&gt;&#x2009;Cys carriers</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">3.58*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">80</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.81</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">Esslinger et al. (<xref ref-type=\"bibr\" rid=\"B10\">2009</xref>)</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>ZNF804A</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">R.
        dlPFC &#x2013; L. hippocampus, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.98<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">115</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.75</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; R. dlPFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.05<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">115</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.77</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; L. dlPFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.59<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">115</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.68</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Esslinger et
        al. (<xref ref-type=\"bibr\" rid=\"B9\">2011</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>ZNF804A</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">R.
        dlPFC &#x2013; L. MFG, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">5.09<sup>&#x2021;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">111</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.98</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; R. MFG, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.68<sup>&#x2021;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">111</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.9</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; R. SFG, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.5<sup>&#x2021;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">111</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.86</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; L. MFG, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.9<sup>&#x2021;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">111</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.74</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; L. hippocampus, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.28<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">111</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.82</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013; R. hippocampus, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.34<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">111</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.64</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Walter et al.
        (<xref ref-type=\"bibr\" rid=\"B72\">2011</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>ZNF804A</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">L.
        TPJ &#x2013; L. inferior frontal gyrus, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.77*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.73</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">L. TPJ &#x2013; L. cuneus, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.76*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.73</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">L. TPJ &#x2013; R. thalamus, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.68*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.72</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">L. TPJ &#x2013; L. caudatetail, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.96*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.77</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">R. dlPFC &#x2013; R. precentral gyrus, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.27*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.83</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">R. dlPFC &#x2013; L. MTG, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.32*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.65</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">R. dlPFC &#x2013; L. LG, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.83*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">109</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.74</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Paulus et al. (<xref ref-type=\"bibr\"
        rid=\"B48\">2011</xref>)</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">\n                <italic>ZNF804A</italic>\n              </td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        L. HF, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.3*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.48</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        L. HF, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.22*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.46</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        R. HF, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.85*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.59</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        R. HF, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.19*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.46</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        L. dlPFC, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">3.42*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.71</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        L. dlPFC, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.26*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.47</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        R. dlPFC, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.39*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.5</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        R. dlPFC, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.33*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.49</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        R. dlPFC, AA&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;CC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.33*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.49</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">R. dlPFC &#x2013;
        R. dlPFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.43*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">94</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.51</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">Rasetti et al. (<xref ref-type=\"bibr\" rid=\"B54\">2011</xref>)</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>ZNF804A</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Controls:
        R. dlPFC &#x2013; L. HF, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">2.72*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">96</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.56</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">Controls: R. dlPFC &#x2013; L. dlPFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.65*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">96</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.75</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">Controls: R. dlPFC &#x2013; R. PFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.21*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">96</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.66</td>\n            </tr>\n            <tr>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">Controls: R. dlPFC &#x2013; L. hippocampus, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.74<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">96</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.77</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">Controls: R. dlPFC &#x2013; R. hippocampus, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">2.89<sup>&#x2020;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">96</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.6</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">Siblings: R. dlPFC &#x2013; R. hippocampus, AA
        &#x2013; abnormal coupling</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">SC</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">2.53*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">83</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.57</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Siblings: R. dlPFC &#x2013; L.
        PFC, AA&#x2009;&lt;&#x2009;C carriers</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">SC</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">2.77*</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">83</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.62</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Siblings: R. dlPFC &#x2013; R.
        dlPFC, AA &#x2013; greater task-related modulation of coupling</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">4.36<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">83</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.98</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">Patients: R. dlPFC &#x2013; R. PFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">SC</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">4.58<sup>&#xA7;</sup></td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">33</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">1.65</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">Patients: R. dlPFC &#x2013; L. hippocampus, AA&#x2009;&lt;&#x2009;
        C carriers</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">3.56<sup>&#xA7;</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">33</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.28</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Patients: R. dlPFC &#x2013; L.
        PFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">2.84*</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">33</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">1.02</td>\n
        \           </tr>\n            <tr>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Patients: R.
        dlPFC &#x2013; R. PFC, CC&#x2009;&gt;&#x2009;CA&#x2009;&gt;&#x2009;AA</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">PPI</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">3.40*</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">33</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">1.22</td>\n            </tr>\n          </tbody>\n        </table>\n
        \       <table-wrap-foot>\n          <p><italic><italic>n</italic>, sample
        size; SC, seeded connectivity; PPI, psychophysiological interaction; dlPFC,
        dorsolateral prefrontal cortex; MFG, middle frontal gyrus; SFG, superior frontal
        gyrus; TPJ, temporo-parietal junction; MTG, middle temporal gyrus; LG, lingual
        gyrus; IFG, inferior frontal gyrus; *<italic>p</italic>-value is uncorrected
        for multiple comparisons; <sup>&#x2020;</sup>false discovery rate corrected
        within region of interest; <sup>&#x2021;</sup>false discovery rate corrected
        for whole brain; <sup>&#xA7;</sup>family wise error corrected within region
        of interest</italic>.</p>\n        </table-wrap-foot>\n      </table-wrap>\n
        \     <table-wrap id=\"T2\" position=\"float\">\n        <label>Table 2</label>\n
        \       <caption>\n          <p><bold>Details of the structural connectivity
        studies using DTI included in this meta-analysis</bold>.</p>\n        </caption>\n
        \       <table frame=\"hsides\" rules=\"groups\">\n          <thead>\n            <tr>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">First author
        and date</th>\n              <th align=\"left\" rowspan=\"1\" colspan=\"1\">Gene</th>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">Connectivity</th>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">Statistic (<italic>t</italic>
        or <italic>F</italic>)</th>\n              <th align=\"left\" rowspan=\"1\"
        colspan=\"1\">\n                <italic>N</italic>\n              </th>\n
        \             <th align=\"left\" rowspan=\"1\" colspan=\"1\">Cohen&#x2019;s
        <italic>d</italic></th>\n            </tr>\n          </thead>\n          <tbody>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">McIntosh
        et al. (<xref ref-type=\"bibr\" rid=\"B33\">2008</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>NRG1</italic> SNP8NRG243177</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        ALIC</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;2.65*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">43</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.83</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Winterer
        et al. (<xref ref-type=\"bibr\" rid=\"B74\">2008</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>NRG1</italic> SNP8NRG221533</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        MF subcortical WM</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;4.67***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.35</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Sprooten
        et al. (<xref ref-type=\"bibr\" rid=\"B60\">2009</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>NRG1</italic> SNP8NRG221533</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        left ATR</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;5.52***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">28</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.95</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>NRG1</italic>
        SNP8NRG243177</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced
        FA in left ATR</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;4.69***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">28</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.66</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Wang
        et al. (<xref ref-type=\"bibr\" rid=\"B73\">2009</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>NRG1</italic> SNP8NRG221533</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        anterior cingulum</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;5.27*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">31</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.86</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>NRG1</italic>
        SNP8NRG221533</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced
        FA in anterior cingulum</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;18***</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">34</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">1.54</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Konrad et al.
        (<xref ref-type=\"bibr\" rid=\"B26\">2009</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>ErbB4</italic> rs707284</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;4.24***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.22</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>ErbB4</italic>
        rs758440</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced
        FA in temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;2.81***</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.81</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>ErbB4</italic> rs839541</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;4.31***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.24</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>ErbB4</italic>
        rs839523</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced
        FA in temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;4.73***</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">1.37</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">G-T-G-T versus lower risk</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;3.85***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">32</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.41</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">G-T-G-T versus
        all other</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced
        FA in temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;3.2***</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.92</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">All other versus non-risk</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        temporal lobe WM</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;3.66***</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">50</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.057</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Zuliani
        et al. (<xref ref-type=\"bibr\" rid=\"B76\">2011</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>ErbB4</italic> rs4673628</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        right ALIC</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;3.48*<sup>?</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">36</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.19</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>ErbB4</italic>
        rs4673629</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced
        FA in left ALIC</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;3.98*<sup>?</sup></td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">36</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.37</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Thomason
        et al. (<xref ref-type=\"bibr\" rid=\"B67\">2010</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>COMT</italic> val158met</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Main effect of
        genotype on FA, AD, RD in GCC</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;3.04*</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">40</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.76</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>COMT</italic> val158met</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Main effect of
        genotype on FA, AD, RD in ATR</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;2.79*</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">40</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.7</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>COMT</italic> val158met</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Main effect of
        genotype on FA, AD, RD in UF</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;2.47*</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">40</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.6</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Liu et al. (<xref
        ref-type=\"bibr\" rid=\"B31\">2010</xref>)</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"><italic>COMT</italic> val158met</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Decreased FA in right CST for Val/Val
        carriers</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;5.197*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">79</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.51</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">LPS, HPS and
        APS haplotypes</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Association
        with mean FA in left PF lobe</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;2.79*</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">68</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.38</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">LPS, HPS and APS haplotypes</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Association with
        mean FA in right PF lobe</td>\n              <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;3.58*</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">68</td>\n              <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.47</td>\n            </tr>\n            <tr>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">LPS, HPS and APS haplotypes</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Association with
        mean FA in right UF</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;3.507*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">68</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.47</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Roffman
        et al. (<xref ref-type=\"bibr\" rid=\"B55\">2011</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>MTHFR</italic> 677T</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">Reduced FA in
        bilateral DACC</td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>F</italic>&#x2009;=&#x2009;6.59*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">18</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">1.29</td>\n            </tr>\n
        \           <tr>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Pacheco
        et al. (<xref ref-type=\"bibr\" rid=\"B47\">2009</xref>)</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">\n                <italic>5-HTTLPR</italic>\n
        \             </td>\n              <td align=\"left\" rowspan=\"1\" colspan=\"1\">Increasing
        number of low expressing alleles &#x2013; decreasing FA in left FUF</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>t</italic>&#x2009;=&#x2009;&#x2212;3.03*</td>\n
        \             <td align=\"left\" rowspan=\"1\" colspan=\"1\">37</td>\n              <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">&#x2212;0.92</td>\n            </tr>\n
        \         </tbody>\n        </table>\n        <table-wrap-foot>\n          <p><italic>n</italic>,
        sample size; FA, fractional anisotropy; MF, medial frontal; WM, white matter;
        ALIC, anterior limb of internal capsule; AD, axial diffusivity; RD, radial
        diffusivity; ATR, anterior thalamic radiation; UF,uncinate fasciculus; GCC,
        genu of corpus callosum; CST, corticospinal tract; PF, prefrontal; DACC, dorsal
        anterior cingulate cortex; FUF, frontal uncinate fasciculus; *<italic>p</italic>&#x2009;&lt;&#x2009;0.05;
        ***<italic>p</italic>&#x2009;&lt;&#x2009;0.001; *<sup>?</sup><italic>p</italic>&#x2009;&lt;&#x2009;0.05
        family wise error corrected</p>\n        </table-wrap-foot>\n      </table-wrap>\n
        \     <sec>\n        <title>Functional connectivity</title>\n        <p>A
        total of 44 effect sizes were calculated from the functional connectivity
        studies. Effect sizes (i.e., Cohen&#x2019;s <italic>d</italic>) ranged from
        medium to large (<italic>d&#x2009;</italic>=&#x2009;0.46&#x2013;1.65) with
        an average effect size of 0.76 (SD&#x2009;&#xB1;&#x2009;0.23). The largest
        effect size (<italic>d&#x2009;</italic>=&#x2009;1.65) was reported for the
        impact of a single nucleotide polymorphism (SNP) in <italic>ZNF804A</italic>
        on functional connectivity within the right PFC in SZ patients (Rasetti et
        al., <xref ref-type=\"bibr\" rid=\"B54\">2011</xref>). While large effect
        sizes (<italic>d&#x2009;</italic>&gt;&#x2009;0.7) were also calculated in
        other studies examining the effects of this SNP on functional connectivity
        (Esslinger et al., <xref ref-type=\"bibr\" rid=\"B10\">2009</xref>, <xref
        ref-type=\"bibr\" rid=\"B9\">2011</xref>; Rasetti et al., <xref ref-type=\"bibr\"
        rid=\"B54\">2011</xref>) these results were not consistent: the smallest effect
        size was also reported for this SNP (<italic>d&#x2009;</italic>=&#x2009;0.46;
        Paulus et al., <xref ref-type=\"bibr\" rid=\"B48\">2011</xref>).</p>\n      </sec>\n
        \     <sec>\n        <title>Structural connectivity</title>\n        <p>A
        total of 24 effect sizes were calculated for structural connectivity investigations.
        Effect sizes ranged from small to large (<italic>d&#x2009;</italic>=&#x2009;0.38&#x2013;1.95)
        with an average effect size of 1.04 (SD&#x2009;=&#x2009;0.42). The largest
        effect size was revealed for the impact of <italic>NRG1</italic> SNP on WM
        integrity in the left ATR (Sprooten et al., <xref ref-type=\"bibr\" rid=\"B60\">2009</xref>).
        Large effect sizes were also observed for all the other studies examining
        the impact of <italic>NRG1</italic> on WM integrity (all <italic>d&#x2009;</italic>&gt;&#x2009;0.80).
        Similar effect sizes were revealed for studies investigating the ErbB4 gene,
        with Cohen&#x2019;s <italic>d</italic> for these studies ranging from 0.81
        to 1.41. Both the <italic>MTHFR</italic> gene and the <italic>5-HTT</italic>
        gene had large effect sizes of 1.29 and 0.92 respectively. The smallest effect
        size of 0.38 was computed for the effect of a <italic>COMT</italic> haplotype
        on left prefrontal WM integrity. Cohen&#x2019;s d for the <italic>COMT</italic>
        papers ranged from 0.38 to 0.76.</p>\n      </sec>\n      <sec>\n        <title>Meta-analysis</title>\n
        \       <p>In our first meta-analysis we considered only the largest effect
        sizes in each study (Figure <xref ref-type=\"fig\" rid=\"F1\">1</xref>; Table
        <xref ref-type=\"table\" rid=\"T3\">3</xref>). This analysis revealed no significant
        difference in outcome variability between the effect sizes for functional
        and structural studies (<italic>Q</italic>&#x2009;=&#x2009;2.171, <italic>p</italic>&#x2009;=&#x2009;0.141).
        Our second analysis examined all of the effects for each result in each paper
        (Figure <xref ref-type=\"fig\" rid=\"F2\">2</xref>; Table <xref ref-type=\"table\"
        rid=\"T3\">3</xref>). This analysis revealed a significant difference between
        effects sizes in functional and structural studies (<italic>Q</italic>&#x2009;=&#x2009;6.928,
        <italic>p</italic>&#x2009;=&#x2009;0.008).</p>\n        <fig id=\"F1\" position=\"float\">\n
        \         <label>Figure 1</label>\n          <caption>\n            <p><bold>Forest
        plot reporting Hedges&#x2019; <italic>g</italic> and 95% CI for the analysis
        showing the largest effect size in each paper</bold>. CI, confidence interval;
        g, Hedges&#x2019; <italic>g</italic>; SE, standard error.</p>\n          </caption>\n
        \         <graphic xlink:href=\"fpsyt-03-00018-g001\"/>\n        </fig>\n
        \       <table-wrap id=\"T3\" position=\"float\">\n          <label>Table
        3</label>\n          <caption>\n            <p><bold>Results of random-effects
        meta-analysis comparing the relative difference in the impact of variants
        on functional and structural connectivity</bold>.</p>\n          </caption>\n
        \         <table frame=\"hsides\" rules=\"groups\">\n            <thead>\n
        \             <tr>\n                <th align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \               <th colspan=\"6\" align=\"center\" rowspan=\"1\">Effect size
        and 95% confidence interval<hr/></th>\n                <th colspan=\"3\" align=\"center\"
        rowspan=\"1\">Heterogeneity<hr/></th>\n              </tr>\n              <tr>\n
        \               <th align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n                <th
        align=\"left\" rowspan=\"1\" colspan=\"1\">No. of studies</th>\n                <th
        align=\"left\" rowspan=\"1\" colspan=\"1\">Point estimate</th>\n                <th
        align=\"left\" rowspan=\"1\" colspan=\"1\">SE</th>\n                <th align=\"left\"
        rowspan=\"1\" colspan=\"1\">Variance</th>\n                <th align=\"left\"
        rowspan=\"1\" colspan=\"1\">Lower limit</th>\n                <th align=\"left\"
        rowspan=\"1\" colspan=\"1\">Upper limit</th>\n                <th align=\"left\"
        rowspan=\"1\" colspan=\"1\"><italic>Q</italic>-value</th>\n                <th
        align=\"left\" rowspan=\"1\" colspan=\"1\">d<italic>f</italic> (<italic>Q</italic>)</th>\n
        \               <th align=\"left\" rowspan=\"1\" colspan=\"1\"><italic>p</italic>-value</th>\n
        \             </tr>\n            </thead>\n            <tbody>\n              <tr
        style=\"background-color:DarkGray;\">\n                <td colspan=\"10\"
        align=\"left\" rowspan=\"1\">\n                  <bold>MAXIMUM ESTIMATE</bold>\n
        \               </td>\n              </tr>\n              <tr>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Functional</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">9</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.812</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.072</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.005</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.671</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.953</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             </tr>\n              <tr>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">Structural</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">10</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">1.067</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.158</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.025</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.758</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">0.377</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n              </tr>\n
        \             <tr>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\">Total
        between</td>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\">2.171</td>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\">1</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.141</td>\n              </tr>\n
        \             <tr style=\"background-color:DarkGray;\">\n                <td
        colspan=\"10\" align=\"left\" rowspan=\"1\">\n                  <bold>ALL
        ESTIMATES</bold>\n                </td>\n              </tr>\n              <tr>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\">Functional</td>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\">44</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.687</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.032</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.001</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.625</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">0.750</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n              </tr>\n              <tr>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">Structural</td>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\">24</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.934</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.088</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.008</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">0.761</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">1.108</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \             </tr>\n              <tr>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\">Total between</td>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n
        \               <td align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n                <td
        align=\"left\" rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\"
        rowspan=\"1\" colspan=\"1\"/>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">6.928</td>\n                <td align=\"left\" rowspan=\"1\"
        colspan=\"1\">1</td>\n                <td align=\"left\" rowspan=\"1\" colspan=\"1\">0.008</td>\n
        \             </tr>\n            </tbody>\n          </table>\n        </table-wrap>\n
        \       <fig id=\"F2\" position=\"float\">\n          <label>Figure 2</label>\n
        \         <caption>\n            <p><bold>Forest plot reporting Hedges&#x2019;
        <italic>g</italic> and 95% CI for each functional and structural connectivity
        analysis</bold>. CI, confidence interval; g, Hedges&#x2019; <italic>g</italic>;
        SE, standard error.</p>\n          </caption>\n          <graphic xlink:href=\"fpsyt-03-00018-g002\"/>\n
        \       </fig>\n      </sec>\n    </sec>\n    <sec>\n      <title>Discussion</title>\n
        \     <p>The aim of this review was to consider the nature and magnitude of
        effect of SZ risk variants on functional and structural connectivity. Our
        focus was the overall magnitude of such effects, rather than delineating the
        direction of effect of a specific variant. Therefore, we focused on the size,
        rather than the direction of individuals results. Examining the effect of
        risk variants on connectivity in fMRI and DTI studies, we found that variation
        in genes implicated in neurotransmission, plasticity, development and myelin
        function are associated with altered neural connectivity. Meta-analyses of
        effect size data revealed that there was no significant difference between
        the effect sizes of functional and structural studies when the largest effect
        size of each study was analyzed. However, when all effects were taken into
        consideration, the effect sizes for the structural studies were larger than
        in the functional connectivity studies, and there was a significant lack of
        homogeneity across the modalities. Mostly likely, given the absence of difference
        when only the largest effects from each set of studies are considered, this
        difference reflects the greater variation in effect sizes in structural studies
        compared to fMRI studies.</p>\n      <sec>\n        <title>Functional connectivity
        studies</title>\n        <p>To date, the effects on functional connectivity
        of a number of candidate SZ genes (<italic>DISC1</italic>, <italic>PRODH</italic>,
        <italic>PPP1R1B</italic>) and one gene with genome-wide significance for SZ
        risk (<italic>ZNF804A</italic>), each of which were found to be associated
        with altered functional connectivity. The mean effect size for the functional
        connectivity studies was large (<italic>d</italic>&#x2009;=&#x2009;0.76),
        with the largest effect size reported for the impact of the rs1344706 variant
        in <italic>ZNF804A</italic>.The ZNF804A risk variant rs1344706 has become
        the focus of much interest in SZ research over the last 3&#x2009;years, as
        GWAS and follow-up analyses have established strong evidence for a link between
        this variant and risk for the disorder (O&#x2019;Donovan et al., <xref ref-type=\"bibr\"
        rid=\"B45\">2008</xref>). While the function of the <italic>ZNF804A</italic>
        gene is unknown, it has been speculated to play a role in gene regulation
        (O&#x2019;Donovan et al., <xref ref-type=\"bibr\" rid=\"B45\">2008</xref>)
        and glutamate and dopamine transmission (Esslinger et al., <xref ref-type=\"bibr\"
        rid=\"B10\">2009</xref>). ZNF804A represents the only SZ-implicated gene that
        we are aware of whose effects on functional connectivity have been investigated
        now on a number of occasions. Importantly, the size of effect reported for
        this variant has varied considerably. For example, as well as having the highest
        effect of the variants considered it also has the lowest effect of the variants
        considered (<italic>d</italic>&#x2009;=&#x2009;0.46; Paulus et al., <xref
        ref-type=\"bibr\" rid=\"B48\">2011</xref>), suggesting that establishing the
        true effect of any variant on functional connectivity will require investigation
        in multiple and adequately powered cohorts. Variants from the candidate SZ
        gene literature by comparison, while each showing large effects on functional
        connectivity (<italic>d</italic>-range: 0.73&#x2013;0.87), have each only
        been the subject of single studies to date (<italic>DISC1</italic>; Di Giorgio
        et al., <xref ref-type=\"bibr\" rid=\"B7\">2008</xref>; <italic>PRODH</italic>;
        Kempf et al., <xref ref-type=\"bibr\" rid=\"B25\">2008</xref>; <italic>PPP1R1B</italic>;
        Meyer-Lindenberg et al., <xref ref-type=\"bibr\" rid=\"B38\">2007</xref>).</p>\n
        \       <p>In 10 of the 12 fMRI studies included in this review, SZ risk variants
        were reported to affect functional circuits that included the PFC during the
        performance of a variety of tasks, such as memory encoding and retrieval,
        working memory, emotion processing, and during rest. These findings reflect
        the PFC&#x2019;s dominant role in many processes related to higher cognitive
        functioning, making it consistently implicated in SZ pathogenesis (Callicott
        et al., <xref ref-type=\"bibr\" rid=\"B4\">2000</xref>).There are several
        possibilities for why PFC function is altered in SZ as reflected in these
        studies. For example, the &#x201C;<italic>reduced neuropil hypothesis</italic>&#x201D;
        of schizophrenia suggests that reduced PFC gray matter (observed in the absence
        of a concomitant change in cell numbers)may reflect decreased dendritic spines/axon
        terminals; the inefficiencies synaptic transmission expected to result may
        well lead to the altered functional connectivity patterns seen here (Selemon
        and Goldman-Rakic, <xref ref-type=\"bibr\" rid=\"B58\">1999</xref>).</p>\n
        \     </sec>\n      <sec>\n        <title>Structural connectivity studies</title>\n
        \       <p>A number of candidate SZ risk genes have been investigated in terms
        of their effects on structural connectivity. This includes genes that are
        involved in myelination (<italic>NRG1, ErbB4</italic>) neurotransmission (<italic>COMT,
        MTHFR, 5-HTTLPR</italic>) and neurodevelopment (<italic>BDNF</italic> and
        <italic>DISC1</italic>). Almost all variants considered here were associated
        with significant variation in FA scores using DTI.</p>\n        <p>The average
        effect size for these studies was large, with the largest effect size computed
        for the impact of NRG1 on FA in the left ATR (Sprooten et al., <xref ref-type=\"bibr\"
        rid=\"B60\">2009</xref>). The NRG1 gene codes for the <italic>NRG1</italic>
        protein, that is involved in growth and differentiation of neuronal and glial
        cells and is necessary for the normal development of the nervous system. <italic>ErbB4</italic>
        is a receptor for the <italic>NRG1</italic> protein. It is thought that NRG1
        may mediate its effects on SZ susceptibility through functional interaction
        with ErbB4 (Norton et al., <xref ref-type=\"bibr\" rid=\"B44\">2006</xref>).
        Interestingly, ErbB4 was also observed here to show effects on WM integrity
        that would be considered to be in of large magnitude. The role of these genes
        in myelin function suggests a mechanism by which they confer risk for SZ.
        The relatively large impact of these genes on structural connectivity, noted
        here, suggests that genetically mediated &#x201C;dysconnectivity&#x201D; in
        SZ results from macro-circuit WM abnormalities in addition to micro-circuit
        synaptic plasticity. However, since oligodendrocyte dysfunction may also impact
        synaptic function and information processing via a myelin-dependent impact
        on synaptic plasticity (Fields, <xref ref-type=\"bibr\" rid=\"B11\">2008</xref>),
        it remains to be established if the influence of these variants is specific
        to structural connectivity or if they also impact upon functional connectivity.</p>\n
        \       <p>Other gene variants associated with variation in WM connectivity
        included COMT, MTHFR, 5-HTTLPR, BDNF and DISC1. Results for both the <italic>MTHFR</italic>
        gene and the <italic>5-HTT</italic> gene had large effect sizes. The <italic>MTHFR</italic>
        gene codes for the an enzyme that plays a role in the regulation of intracellular
        methylation reactions and may influence dopamine signaling (Roffman et al.,
        <xref ref-type=\"bibr\" rid=\"B56\">2008</xref>). The hypofunctional 677T
        variant of this gene has been associated with increased SZ risk (Gilbody et
        al., <xref ref-type=\"bibr\" rid=\"B16\">2007</xref>). The reuptake of serotonin
        to the presynaptic neuron for recycling or degradation after serotonin release
        is regulated by the serotonin transporter (<italic>5-HTT)</italic>. Although
        the <italic>5-HTTLPR</italic> polymorphism has been found to be associated
        with SZ in a South India population (Vijayan et al., <xref ref-type=\"bibr\"
        rid=\"B71\">2009</xref>), other genetic association studies have given conflicting
        results (Rao et al., <xref ref-type=\"bibr\" rid=\"B53\">1998</xref>). The
        smallest effect size was computed for the effect of a <italic>COMT</italic>
        haplotype on left prefrontal WM integrity (Liu et al., <xref ref-type=\"bibr\"
        rid=\"B31\">2010</xref>). The COMT gene codes for an enzyme that is involved
        in the degradation of dopamine. Therefore, the evidence from DTI studies investigating
        the impact of the COMT gene on WM indicates that neurosignalling processes
        involved in SZ may also impact structural connectivity. Finally, <italic>BDNF</italic>
        (Chiang et al., <xref ref-type=\"bibr\" rid=\"B5\">2011</xref>) and <italic>DISC1</italic>
        (Sprooten et al., <xref ref-type=\"bibr\" rid=\"B61\">2011</xref>) which are
        genes that are crucial for neurodevelopment, were also associated with WM
        connectivity in SZ. However, as insufficient data was available, effect sizes
        for these studies were not calculated.</p>\n      </sec>\n      <sec>\n        <title>Meta-analysis</title>\n
        \       <p>The papers included in this review most commonly report a large
        effect of gene variants on functional and structural connectivity. This result
        is similar to previous meta-analyses in imaging genetics, which reported large
        effect sizes of gene variants (i.e., <italic>5-HTTLPR</italic> polymorphism
        and the <italic>COMT</italic> Val158Met polymorphism) on brain function (Munafo
        et al., <xref ref-type=\"bibr\" rid=\"B41\">2008</xref>; Mier et al., <xref
        ref-type=\"bibr\" rid=\"B40\">2010</xref>). This result is also consistent
        with the intermediate phenotype hypothesis that common SZ risk variants will
        show small effects on behavior and disease risk, but large effects at the
        level of the brain (Tost et al., <xref ref-type=\"bibr\" rid=\"B68\">2011</xref>).</p>\n
        \       <p>When the maximum effect size value for each paper in our meta-analysis
        was compared between fMRI and DTI studies, no significant difference was found
        between these measures. As only a small number of studies were obtained, there
        may be a lack of power to detect such differences. However, examination of
        effect sizes for all significant effects indicate that structural connectivity
        studies were associated with overall larger and more variable effect sizes.
        This suggests that measures of structural connectivity, such as DTI, may be
        sensitive to a wider range of effects compared to functional connectivity
        measures, which may only be able to accurately detect large effects. This
        result may also indicate that structural connectivity is closer to the level
        of genes than functional connectivity.</p>\n      </sec>\n      <sec>\n        <title>Limitations</title>\n
        \       <p>A number of limitations need to be considered in evaluating the
        findings of the present study. Firstly, many of the studies included in the
        meta-analysis have examined the effects of polymorphisms that do not have
        consistent association with SZ phenotypes. This makes it difficult to determine
        the relevance of these genes for our understanding of SZ pathogenesis (for
        a review, see Meyer-Lindenberg, <xref ref-type=\"bibr\" rid=\"B36\">2010</xref>).
        Secondly, it should also be noted that the sample sizes included in these
        studies are relatively small and thus, are under powered to detect differences
        in brain connectivity conferred by individual variants. Due to the interplay
        between sample size, power, and effect size, smaller studies generally show
        larger effects in meta-analyses (Sterne et al., <xref ref-type=\"bibr\" rid=\"B63\">2000</xref>)
        and may lack sufficient power to detect smaller effects. Related to the general
        issue of sample size, it is important to note that the average sample size
        of the studies utilizing DTI was smaller than that for the functional studies.
        As a result, the effect sizes for the structural papers may be over-inflated.
        However, the results of our meta-analysis suggest that despite smaller samples,
        the structural imaging studies were associated with a wider range of effects,
        suggesting that sample size is not the only factor at play here.</p>\n        <p>Due
        to the under-representation of publications with negative results, the studies
        included in this review may not be representative of connectivity research
        in its entirety, but rather a bias toward only publish papers showing statistically
        significant results. Therefore, while our effect size findings are calculated
        on the basis of published effect sizes, it is possible that the true effect
        sizes are smaller, and to an extent that is unknown. Similarly, it is also
        unclear to what extent differences in scanning parameters between the studies
        included in this meta-analysis influenced results. More systematic investigation
        of these differences will in the future be possible with the accumulation
        of more studies.</p>\n        <p>An additional limitation in the studies considered
        here is that each investigation examined the effects of only one particular
        variant. However, the true function of these genes may be affected by additive
        or epistatic interactions with other variants. As such, the results presented
        in this review may be incomplete without taking these interactions into account
        (Nicodemus et al., <xref ref-type=\"bibr\" rid=\"B43\">2010</xref>).</p>\n
        \       <p>Finally, it is probable that these results could be impacted by
        differences in functional and structural methodological approaches. For example,
        a number of analysis methods can be employed to measure functional connectivity
        between brain regions. However, we are not currently aware of the relative
        strengths and weaknesses of these different approaches. There are also various
        approaches used to quantify WM connectivity using DTI, which also pose different
        strengths and limitations (see Jones, <xref ref-type=\"bibr\" rid=\"B23\">2010</xref>
        for a review).</p>\n      </sec>\n      <sec>\n        <title>Conclusions
        and future directions</title>\n        <p>In a short period of time, imaging
        genetics has made important progress in delineating genetic effects on neural
        connectivity. In particular, it has established neural connectivity as a key
        intermediate phenotype for SZ, which can be used to explore the complex trajectory
        from genetic risk to clinical symptoms.</p>\n        <p>Despite the progress
        that has taken place, we believe important advances can be made in this research
        field in four key areas. Firstly, future studies should examine the effects
        of gene variants on neural connectivity in larger sample sizes, as this can
        provide the extra statistical power that may be necessary to detect smaller
        effects of these genes. Multi-site research projects, such as the IMAGEN project
        in Europe, may be particularly suited for compiling imaging and genetic databases
        of thousands of subjects (Schumann et al., <xref ref-type=\"bibr\" rid=\"B57\">2010</xref>).
        Secondly, future studies should examine additive and epistatic effects of
        gene variants on neural connectivity, as these variants are unlikely to be
        working in isolation. Thirdly, future studies should examine the effects of
        risk variants in healthy controls and SZ patients as the opposite effects
        of these genes on connectivity can be found in these different groups (e.g.,
        Prata et al., <xref ref-type=\"bibr\" rid=\"B52\">2009</xref>).</p>\n        <p>Finally,
        future studies could benefit from the novel application of recently developed
        analysis techniques to imaging genetics. For example, DCM hold potential for
        constructing models of changing brain interactions that also take into account
        genetic variation (Meyer-Lindenberg, <xref ref-type=\"bibr\" rid=\"B35\">2009</xref>).
        Other recent advances include the use of parallel ICA to simultaneously analyze
        independent components derived from fMRI and genetic data (Liu et al., <xref
        ref-type=\"bibr\" rid=\"B32\">2009</xref>). For example, Meda et al. (<xref
        ref-type=\"bibr\" rid=\"B34\">2010</xref>) used this technique in a pilot
        study to identify simultaneous independent components of fMRI data and SNP
        data, derived from a sample of 35 controls and 31 SZ patients. The authors
        found correlations between different neural networks and a number of SNPs,
        including polymorphisms involved in altered dopamine transmission. While the
        authors only included a small number of SNPs and a small sample size, this
        research suggests a powerful new approach for future studies examining the
        effects of SZ risk variants on functional brain networks. Similarly, more
        advanced DTI techniques could be implemented that use high angular resolution
        to account for multiple crossing fibers within a single voxel. Such imaging
        techniques include Q-space approaches and mixture models (Tournier et al.,
        <xref ref-type=\"bibr\" rid=\"B69\">2011</xref>). These models provide mathematical
        alternatives to the tensor model for the characterization of diffusion processes.
        Furthermore, Jones (<xref ref-type=\"bibr\" rid=\"B23\">2010</xref>) recommends
        the integration of DTI with other measures of WM such as measures of axon
        density and myelination that can be acquired using techniques such as magnetization
        transfer or multicomponent relaxometry.</p>\n        <p>In conclusion, the
        present meta-analysis examined the nature and magnitude of effect of SZ risk
        variants on functional and structural connectivity. Gene variants impacting
        upon both synaptic plasticity and axonal connectivity have been associated
        with altered neural connectivity in patients and healthy controls. As such,
        it is likely that both mechanisms make important contributions to SZ pathogenesis.
        On average, risk variants exert a large effect on functional and structural
        connectivity. There is also more variability in the effects of variants on
        structural connectivity, compared to functional connectivity. While imaging
        genetics has made considerable progress in the field of neural connectivity
        in a short period of time, important advances are still to be made. It is
        hoped that this research will lead to a better understanding of the biological
        mechanisms mediating genetic risk for SZ, which can then be used to direct
        novel treatments for the disorder.</p>\n      </sec>\n    </sec>\n    <sec>\n
        \     <title>Conflict of Interest Statement</title>\n      <p>The authors
        declare that the research was conducted in the absence of any commercial or
        financial relationships that could be construed as a potential conflict of
        interest.</p>\n    </sec>\n  </body>\n  <back>\n    <ack>\n      <p>This work
        was supported by a Science Foundation Ireland research award to Professor
        Aiden Corvin (SFI08/IN.1/B1916-Corvin).</p>\n    </ack>\n    <ref-list>\n
        \     <title>References</title>\n      <ref id=\"B1\">\n        <mixed-citation
        publication-type=\"journal\"><person-group person-group-type=\"author\"><name><surname>Braff</surname><given-names>D.
        L.</given-names></name><name><surname>Freedman</surname><given-names>R.</given-names></name><name><surname>Schork</surname><given-names>N.
        J.</given-names></name><name><surname>Gottesman</surname><given-names>I. I.</given-names></name></person-group>
        (<year>2007</year>). <article-title>Deconstructing schizophrenia: an overview
        of the use of endophenotypes in order to understand a complex disorder</article-title>.
        <source>Schizophr. Bull.</source>\n<volume>33</volume>, <fpage>21</fpage><pub-id
        pub-id-type=\"doi\">10.1093/schbul/sbl049</pub-id><pub-id pub-id-type=\"pmid\">17088422</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B2\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Breakspear</surname><given-names>M.</given-names></name><name><surname>Terry</surname><given-names>J.
        R.</given-names></name><name><surname>Friston</surname><given-names>K. J.</given-names></name><name><surname>Harris</surname><given-names>A.
        W.</given-names></name><name><surname>Williams</surname><given-names>L. M.</given-names></name><name><surname>Brown</surname><given-names>K.</given-names></name><name><surname>Brennan</surname><given-names>J.</given-names></name><name><surname>Gordon</surname><given-names>E.</given-names></name></person-group>
        (<year>2003</year>). <article-title>A disturbance of nonlinear interdependence
        in scalp EEG of subjects with first episode schizophrenia</article-title>.
        <source>Neuroimage</source>\n<volume>20</volume>, <fpage>466</fpage>&#x2013;<lpage>478</lpage><pub-id
        pub-id-type=\"doi\">10.1016/S1053-8119(03)00332-X</pub-id><pub-id pub-id-type=\"pmid\">14527607</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B3\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Buchsbaum</surname><given-names>M.
        S.</given-names></name><name><surname>Schoenknecht</surname><given-names>P.</given-names></name><name><surname>Torosjan</surname><given-names>Y.</given-names></name><name><surname>Newmark</surname><given-names>R.</given-names></name><name><surname>Chu</surname><given-names>K.
        W.</given-names></name><name><surname>Mitelman</surname><given-names>S.</given-names></name><name><surname>Brickman</surname><given-names>A.
        M.</given-names></name><name><surname>Shihabuddin</surname><given-names>L.</given-names></name><name><surname>Haznedar</surname><given-names>M.
        M.</given-names></name><name><surname>Hazlett</surname><given-names>E. A.</given-names></name><name><surname>Ahmed</surname><given-names>S.</given-names></name><name><surname>Tang</surname><given-names>C.</given-names></name></person-group>
        (<year>2006</year>). <article-title>Diffusion tensor imaging of frontal lobe
        white matter tracts in schizophrenia</article-title>. <source>Ann. Gen. Psychiatry</source>\n<volume>5</volume>,
        <fpage>19</fpage><pub-id pub-id-type=\"doi\">10.1186/1744-859X-5-19</pub-id><pub-id
        pub-id-type=\"pmid\">17132158</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B4\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Callicott</surname><given-names>J.
        H.</given-names></name><name><surname>Bertolino</surname><given-names>A.</given-names></name><name><surname>Mattay</surname><given-names>V.
        S.</given-names></name><name><surname>Langheim</surname><given-names>F. J.</given-names></name><name><surname>Duyn</surname><given-names>J.</given-names></name><name><surname>Coppola</surname><given-names>R.</given-names></name><name><surname>Goldberg</surname><given-names>T.
        E.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name></person-group> (<year>2000</year>). <article-title>Physiological
        dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited</article-title>.
        <source>Cereb. Cortex</source>\n<volume>10</volume>, <fpage>1078</fpage>&#x2013;<lpage>1092</lpage><pub-id
        pub-id-type=\"doi\">10.1093/cercor/10.11.1078</pub-id><pub-id pub-id-type=\"pmid\">11053229</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B5\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Chiang</surname><given-names>M.
        C.</given-names></name><name><surname>Barysheva</surname><given-names>M.</given-names></name><name><surname>Toga</surname><given-names>A.
        W.</given-names></name><name><surname>Medland</surname><given-names>S. E.</given-names></name><name><surname>Hansell</surname><given-names>N.
        K.</given-names></name><name><surname>James</surname><given-names>M. R.</given-names></name><name><surname>McMahon</surname><given-names>K.
        L.</given-names></name><name><surname>de Zubicatay</surname><given-names>G.
        I.</given-names></name><name><surname>Martin</surname><given-names>N. G.</given-names></name><name><surname>Wright</surname><given-names>M.
        J.</given-names></name><name><surname>Thompson</surname><given-names>P. M.</given-names></name></person-group>
        (<year>2011</year>). <article-title>BDNF gene effects on brain circuitry replicated
        in 455 twins</article-title>. <source>Neuroimage</source>\n<volume>55</volume>,
        <fpage>448</fpage>&#x2013;<lpage>454</lpage><pub-id pub-id-type=\"doi\">10.1016/j.neuroimage.2010.12.053</pub-id><pub-id
        pub-id-type=\"pmid\">21195196</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B6\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Davis</surname><given-names>K.
        L.</given-names></name><name><surname>Stewart</surname><given-names>D. G.</given-names></name><name><surname>Friedman</surname><given-names>J.
        I.</given-names></name><name><surname>Buchsbaum</surname><given-names>M.</given-names></name><name><surname>Harvey</surname><given-names>P.
        D.</given-names></name><name><surname>Hof</surname><given-names>P. R.</given-names></name><name><surname>Buxbaum</surname><given-names>J.</given-names></name><name><surname>Haroutunian</surname><given-names>V.</given-names></name></person-group>
        (<year>2003</year>). <article-title>White matter changes in schizophrenia:
        evidence for myelin-related dysfunction</article-title>. <source>Arch. Gen.
        Psychiatry</source>\n<volume>60</volume>, <fpage>443</fpage>&#x2013;<lpage>456</lpage><pub-id
        pub-id-type=\"doi\">10.1001/archpsyc.60.5.443</pub-id><pub-id pub-id-type=\"pmid\">12742865</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B7\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Di Giorgio</surname><given-names>A.</given-names></name><name><surname>Blasi</surname><given-names>G.</given-names></name><name><surname>Sambataro</surname><given-names>F.</given-names></name><name><surname>Rampino</surname><given-names>A.</given-names></name><name><surname>Papazacharias</surname><given-names>A.</given-names></name><name><surname>Gambi</surname><given-names>F.</given-names></name><name><surname>Romano</surname><given-names>R.</given-names></name><name><surname>Caforio</surname><given-names>G.</given-names></name><name><surname>Rizzo</surname><given-names>M.</given-names></name><name><surname>Latorre</surname><given-names>V.</given-names></name><name><surname>Popolizio</surname><given-names>T.</given-names></name><name><surname>Kolachana</surname><given-names>B.</given-names></name><name><surname>Callicott</surname><given-names>J.
        H.</given-names></name><name><surname>Nardini</surname><given-names>M.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name><name><surname>Bertolino</surname><given-names>A.</given-names></name></person-group>
        (<year>2008</year>). <article-title>Association of the SerCys DISC1 polymorphism
        with human hippocampal formation gray matter and function during memory encoding</article-title>.
        <source>Eur. J. Neurosci.</source>\n<volume>28</volume>, <fpage>2129</fpage>&#x2013;<lpage>2136</lpage><pub-id
        pub-id-type=\"doi\">10.1111/j.1460-9568.2008.06482.x</pub-id><pub-id pub-id-type=\"pmid\">19046394</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B8\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Ellison-Wright</surname><given-names>I.</given-names></name><name><surname>Bullmore</surname><given-names>E.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Meta-analysis of diffusion tensor imaging
        studies in schizophrenia</article-title>. <source>Schizophr. Res.</source>\n<volume>108</volume>,
        <fpage>3</fpage>&#x2013;<lpage>10</lpage><pub-id pub-id-type=\"doi\">10.1016/j.schres.2008.11.021</pub-id><pub-id
        pub-id-type=\"pmid\">19128945</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B9\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Esslinger</surname><given-names>C.</given-names></name><name><surname>Kirsch</surname><given-names>P.</given-names></name><name><surname>Haddad</surname><given-names>L.</given-names></name><name><surname>Mier</surname><given-names>D.</given-names></name><name><surname>Sauer</surname><given-names>C.</given-names></name><name><surname>Erk</surname><given-names>S.</given-names></name><name><surname>Schnell</surname><given-names>K.</given-names></name><name><surname>Arnold</surname><given-names>C.</given-names></name><name><surname>Witt</surname><given-names>S.
        H.</given-names></name><name><surname>Rietschel</surname><given-names>M.</given-names></name><name><surname>Cichon</surname><given-names>S.</given-names></name><name><surname>Walter</surname><given-names>H.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Cognitive state and connectivity effects
        of the genome-wide significant psychosis variant in ZNF804A</article-title>.
        <source>Neuroimage</source>\n<volume>54</volume>, <fpage>2514</fpage>&#x2013;<lpage>2523</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.neuroimage.2010.10.012</pub-id><pub-id pub-id-type=\"pmid\">20946959</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B10\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Esslinger</surname><given-names>C.</given-names></name><name><surname>Walter</surname><given-names>H.</given-names></name><name><surname>Kirsch</surname><given-names>P.</given-names></name><name><surname>Erk</surname><given-names>S.</given-names></name><name><surname>Schnell</surname><given-names>K.</given-names></name><name><surname>Arnold</surname><given-names>C.</given-names></name><name><surname>Haddad</surname><given-names>L.</given-names></name><name><surname>Mier</surname><given-names>D.</given-names></name><name><surname>Opitz
        Von Boberfeld</surname><given-names>C.</given-names></name><name><surname>Raab</surname><given-names>K.</given-names></name><name><surname>Witt</surname><given-names>S.
        H.</given-names></name><name><surname>Rietschel</surname><given-names>M.</given-names></name><name><surname>Cichon</surname><given-names>S.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Neural mechanisms of a genome-wide supported
        psychosis variant</article-title>. <source>Science</source>\n<volume>324</volume>,
        <fpage>605</fpage><pub-id pub-id-type=\"doi\">10.1126/science.1167768</pub-id><pub-id
        pub-id-type=\"pmid\">19407193</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B11\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Fields</surname><given-names>R.
        D.</given-names></name></person-group> (<year>2008</year>). <article-title>White
        matter in learning, cognition and psychiatric disorders</article-title>. <source>Trends
        Neurosci.</source>\n<volume>31</volume>, <fpage>361</fpage>&#x2013;<lpage>370</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.tins.2008.04.001</pub-id><pub-id pub-id-type=\"pmid\">18538868</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B12\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Friston</surname><given-names>K.
        J.</given-names></name></person-group> (<year>1998</year>). <article-title>The
        disconnection hypothesis</article-title>. <source>Schizophr. Res.</source>\n<volume>30</volume>,
        <fpage>115</fpage>&#x2013;<lpage>125</lpage><pub-id pub-id-type=\"doi\">10.1016/S0920-9964(97)00140-0</pub-id><pub-id
        pub-id-type=\"pmid\">9549774</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B13\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Friston</surname><given-names>K.
        J.</given-names></name><name><surname>Buechel</surname><given-names>C.</given-names></name><name><surname>Fink</surname><given-names>G.
        R.</given-names></name><name><surname>Morris</surname><given-names>J.</given-names></name><name><surname>Rolls</surname><given-names>E.</given-names></name><name><surname>Dolan</surname><given-names>R.
        J.</given-names></name></person-group> (<year>1997</year>). <article-title>Psychophysiological
        and modulatory interactions in neuroimaging</article-title>. <source>Neuroimage</source>\n<volume>6</volume>,
        <fpage>218</fpage>&#x2013;<lpage>229</lpage><pub-id pub-id-type=\"doi\">10.1006/nimg.1997.0291</pub-id><pub-id
        pub-id-type=\"pmid\">9344826</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B14\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Friston</surname><given-names>K.
        J.</given-names></name><name><surname>Frith</surname><given-names>C. D.</given-names></name></person-group>
        (<year>1995</year>). <article-title>Schizophrenia: a disconnection syndrome?</article-title>\n<source>Clin.
        Neurosci.</source>\n<volume>3</volume>, <fpage>89</fpage>&#x2013;<lpage>97</lpage><pub-id
        pub-id-type=\"pmid\">7583624</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B15\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Friston</surname><given-names>K.
        J.</given-names></name><name><surname>Frith</surname><given-names>C. D.</given-names></name><name><surname>Liddle</surname><given-names>P.
        F.</given-names></name><name><surname>Frackowiak</surname><given-names>R.
        S.</given-names></name></person-group> (<year>1993</year>). <article-title>Functional
        connectivity: the principal-component analysis of large (PET) data sets</article-title>.
        <source>J. Cereb. Blood Flow Metab.</source>\n<volume>13</volume>, <fpage>5</fpage>&#x2013;<lpage>14</lpage><pub-id
        pub-id-type=\"doi\">10.1038/jcbfm.1993.133</pub-id><pub-id pub-id-type=\"pmid\">8417010</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B16\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Gilbody</surname><given-names>S.</given-names></name><name><surname>Lewis</surname><given-names>S.</given-names></name><name><surname>Lightfoot</surname><given-names>T.</given-names></name></person-group>
        (<year>2007</year>). <article-title>Methylenetetrahydrofolate reductase (MTHFR)
        genetic polymorphisms and psychiatric disorders: a HuGE review</article-title>.
        <source>Am. J. Epidemiol.</source>\n<volume>165</volume>, <fpage>1</fpage>&#x2013;<lpage>13</lpage><pub-id
        pub-id-type=\"doi\">10.1093/aje/kwj347</pub-id><pub-id pub-id-type=\"pmid\">17074966</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B17\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Gottesman</surname><given-names>I.
        I.</given-names></name><name><surname>Gould</surname><given-names>T. D.</given-names></name></person-group>
        (<year>2003</year>). <article-title>The endophenotype concept in psychiatry:
        etymology and strategic intentions</article-title>. <source>Am. J. Psychiatry</source>\n<volume>160</volume>,
        <fpage>636</fpage>&#x2013;<lpage>645</lpage><pub-id pub-id-type=\"doi\">10.1176/appi.ajp.160.4.636</pub-id><pub-id
        pub-id-type=\"pmid\">12668349</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B18\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Gustavsson</surname><given-names>A.</given-names></name><name><surname>Svensson</surname><given-names>M.</given-names></name><name><surname>Jacobi</surname><given-names>F.</given-names></name><name><surname>Allgulander</surname><given-names>C.</given-names></name><name><surname>Alonso</surname><given-names>J.</given-names></name><name><surname>Beghi</surname><given-names>E.</given-names></name><name><surname>Dodel</surname><given-names>R.</given-names></name><name><surname>Ekman</surname><given-names>M.</given-names></name><name><surname>Faravelli</surname><given-names>C.</given-names></name><name><surname>Fratiglioni</surname><given-names>L.</given-names></name><name><surname>Gannon</surname><given-names>B.</given-names></name><name><surname>Jones</surname><given-names>D.
        H.</given-names></name><name><surname>Jennum</surname><given-names>P.</given-names></name><name><surname>Jordanova</surname><given-names>A.</given-names></name><name><surname>Jonsson</surname><given-names>L.</given-names></name><name><surname>Karampampa</surname><given-names>K.</given-names></name><name><surname>Knapp</surname><given-names>M.</given-names></name><name><surname>Kobelt</surname><given-names>G.</given-names></name><name><surname>Kurth</surname><given-names>T.</given-names></name><name><surname>Lieb</surname><given-names>R.</given-names></name><name><surname>Linde</surname><given-names>M.</given-names></name><name><surname>Ljungcrantz</surname><given-names>C.</given-names></name><name><surname>Maercker</surname><given-names>A.</given-names></name><name><surname>Melin</surname><given-names>B.</given-names></name><name><surname>Moscarelli</surname><given-names>M.</given-names></name><name><surname>Musayev</surname><given-names>A.</given-names></name><name><surname>Norwood</surname><given-names>F.</given-names></name><name><surname>Preisig</surname><given-names>M.</given-names></name><name><surname>Pugliatti</surname><given-names>M.</given-names></name><name><surname>Rehm</surname><given-names>J.</given-names></name><name><surname>Salvador-Carulla</surname><given-names>L.</given-names></name><name><surname>Schlehofer</surname><given-names>B.</given-names></name><name><surname>Simon</surname><given-names>R.</given-names></name><name><surname>Steinhausen</surname><given-names>H.
        C.</given-names></name><name><surname>Stovner</surname><given-names>L. J.</given-names></name><name><surname>Vallat</surname><given-names>J.
        M.</given-names></name><name><surname>Den Bergh</surname><given-names>P. V.</given-names></name><name><surname>Van
        Os</surname><given-names>J.</given-names></name><name><surname>Vos</surname><given-names>P.</given-names></name><name><surname>Xu</surname><given-names>W.</given-names></name><name><surname>Wittchen</surname><given-names>H.
        U.</given-names></name><name><surname>Jonsson</surname><given-names>B.</given-names></name><name><surname>Olesen</surname><given-names>J.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Cost of disorders of the brain in Europe
        2010</article-title>. <source>Eur. Neuropsychopharmacol.</source>\n<volume>21</volume>,
        <fpage>718</fpage>&#x2013;<lpage>779</lpage><pub-id pub-id-type=\"doi\">10.1016/j.euroneuro.2011.08.008</pub-id><pub-id
        pub-id-type=\"pmid\">21924589</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B19\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Hakak</surname><given-names>Y.</given-names></name><name><surname>Walker</surname><given-names>J.
        R.</given-names></name><name><surname>Li</surname><given-names>C.</given-names></name><name><surname>Wong</surname><given-names>W.
        H.</given-names></name><name><surname>Davis</surname><given-names>K. L.</given-names></name><name><surname>Buxbaum</surname><given-names>J.
        D.</given-names></name><name><surname>Haroutunian</surname><given-names>V.</given-names></name><name><surname>Fienberg</surname><given-names>A.
        A.</given-names></name></person-group> (<year>2001</year>). <article-title>Genome-wide
        expression analysis reveals dysregulation of myelination-related genes in
        chronic schizophrenia</article-title>. <source>Proc. Natl. Acad. Sci. U.S.A.</source>\n<volume>98</volume>,
        <fpage>4746</fpage>&#x2013;<lpage>4751</lpage><pub-id pub-id-type=\"doi\">10.1073/pnas.081071198</pub-id><pub-id
        pub-id-type=\"pmid\">11296301</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B20\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Harrison</surname><given-names>P.
        J.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name></person-group> (<year>2005</year>). <article-title>Schizophrenia
        genes, gene expression, and neuropathology: on the matter of their convergence</article-title>.
        <source>Mol. Psychiatry</source>\n<volume>10</volume>, <fpage>40</fpage>&#x2013;<lpage>68</lpage>;
        image 45.<pub-id pub-id-type=\"doi\">10.1038/sj.mp.4001686</pub-id><pub-id
        pub-id-type=\"pmid\">15263907</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B21\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Javitt</surname><given-names>D.
        C.</given-names></name></person-group> (<year>2010</year>). <article-title>Glutamatergic
        theories of schizophrenia</article-title>. <source>Isr. J. Psychiatry Relat.
        Sci.</source>\n<volume>47</volume>, <fpage>4</fpage>&#x2013;<lpage>16</lpage><pub-id
        pub-id-type=\"pmid\">20686195</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B22\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Jones</surname><given-names>D.
        K.</given-names></name></person-group> (<year>2008</year>). <article-title>Studying
        connections in the living human brain with diffusion MRI</article-title>.
        <source>Cortex</source>\n<volume>44</volume>, <fpage>936</fpage>&#x2013;<lpage>952</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.cortex.2008.05.002</pub-id><pub-id pub-id-type=\"pmid\">18635164</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B23\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Jones</surname><given-names>D.
        K.</given-names></name></person-group> (<year>2010</year>). <article-title>Challenges
        and limitations of quantifying brain connectivity in vivo with diffusion MRI</article-title>.
        <source>Imaging</source>\n<volume>2</volume>, <fpage>341</fpage>&#x2013;<lpage>355</lpage><pub-id
        pub-id-type=\"doi\">10.2217/iim.10.21</pub-id></mixed-citation>\n      </ref>\n
        \     <ref id=\"B24\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Kegeles</surname><given-names>L.
        S.</given-names></name><name><surname>Abi-Dargham</surname><given-names>A.</given-names></name><name><surname>Zea-Ponce</surname><given-names>Y.</given-names></name><name><surname>Rodenhiser-Hill</surname><given-names>J.</given-names></name><name><surname>Mann</surname><given-names>J.
        J.</given-names></name><name><surname>Van Heertum</surname><given-names>R.
        L.</given-names></name><name><surname>Cooper</surname><given-names>T. B.</given-names></name><name><surname>Carlsson</surname><given-names>A.</given-names></name><name><surname>Laruelle</surname><given-names>M.</given-names></name></person-group>
        (<year>2000</year>). <article-title>Modulation of amphetamine-induced striatal
        dopamine release by ketamine in humans: implications for schizophrenia</article-title>.
        <source>Biol. Psychiatry</source>\n<volume>48</volume>, <fpage>627</fpage>&#x2013;<lpage>640</lpage><pub-id
        pub-id-type=\"doi\">10.1016/S0006-3223(00)00976-8</pub-id><pub-id pub-id-type=\"pmid\">11032974</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B25\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Kempf</surname><given-names>L.</given-names></name><name><surname>Nicodemus</surname><given-names>K.
        K.</given-names></name><name><surname>Kolachana</surname><given-names>B.</given-names></name><name><surname>Vakkalanka</surname><given-names>R.</given-names></name><name><surname>Verchinski</surname><given-names>B.
        A.</given-names></name><name><surname>Egan</surname><given-names>M. F.</given-names></name><name><surname>Straub</surname><given-names>R.
        E.</given-names></name><name><surname>Mattay</surname><given-names>V. A.</given-names></name><name><surname>Callicott</surname><given-names>J.
        H.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2008</year>). <article-title>Functional polymorphisms in PRODH are
        associated with risk and protection for schizophrenia and fronto-striatal
        structure and function</article-title>. <source>PLoS Genet.</source>\n<volume>4</volume>,
        <fpage>e1000252</fpage><pub-id pub-id-type=\"doi\">10.1371/journal.pgen.1000252</pub-id><pub-id
        pub-id-type=\"pmid\">18989458</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B26\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Konrad</surname><given-names>A.</given-names></name><name><surname>Vucurevic</surname><given-names>G.</given-names></name><name><surname>Musso</surname><given-names>F.</given-names></name><name><surname>Stoeter</surname><given-names>P.</given-names></name><name><surname>Dahmen</surname><given-names>N.</given-names></name><name><surname>Winterer</surname><given-names>G.</given-names></name></person-group>
        (<year>2009</year>). <article-title>ErbB4 genotype predicts left frontotemporal
        structural connectivity in human brain</article-title>. <source>Neuropsychopharmacology</source>\n<volume>34</volume>,
        <fpage>641</fpage>&#x2013;<lpage>650</lpage><pub-id pub-id-type=\"doi\">10.1038/npp.2008.112</pub-id><pub-id
        pub-id-type=\"pmid\">18668031</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B27\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Konrad</surname><given-names>A.</given-names></name><name><surname>Winterer</surname><given-names>G.</given-names></name></person-group>
        (<year>2008</year>). <article-title>Disturbed structural connectivity in schizophrenia
        primary factor in pathology or epiphenomenon?</article-title>\n<source>Schizophr.
        Bull.</source>\n<volume>34</volume>, <fpage>72</fpage>&#x2013;<lpage>92</lpage><pub-id
        pub-id-type=\"doi\">10.1093/schbul/sbm034</pub-id><pub-id pub-id-type=\"pmid\">17485733</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B28\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Kubicki</surname><given-names>M.</given-names></name><name><surname>Mccarley</surname><given-names>R.</given-names></name><name><surname>Westin</surname><given-names>C.
        F.</given-names></name><name><surname>Park</surname><given-names>H. J.</given-names></name><name><surname>Maier</surname><given-names>S.</given-names></name><name><surname>Kikinis</surname><given-names>R.</given-names></name><name><surname>Jolesz</surname><given-names>F.
        A.</given-names></name><name><surname>Shenton</surname><given-names>M. E.</given-names></name></person-group>
        (<year>2007</year>). <article-title>A review of diffusion tensor imaging studies
        in schizophrenia</article-title>. <source>J. Psychiatr. Res.</source>\n<volume>41</volume>,
        <fpage>15</fpage>&#x2013;<lpage>30</lpage><pub-id pub-id-type=\"doi\">10.1016/j.jpsychires.2005.05.005</pub-id><pub-id
        pub-id-type=\"pmid\">16023676</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B29\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Lawrie</surname><given-names>S.
        M.</given-names></name><name><surname>Buechel</surname><given-names>C.</given-names></name><name><surname>Whalley</surname><given-names>H.
        C.</given-names></name><name><surname>Frith</surname><given-names>C. D.</given-names></name><name><surname>Friston</surname><given-names>K.
        J.</given-names></name><name><surname>Johnstone</surname><given-names>E. C.</given-names></name></person-group>
        (<year>2002</year>). <article-title>Reduced frontotemporal functional connectivity
        in schizophrenia associated with auditory hallucinations</article-title>.
        <source>Biol. Psychiatry</source>\n<volume>51</volume>, <fpage>1008</fpage>&#x2013;<lpage>1011</lpage><pub-id
        pub-id-type=\"doi\">10.1016/S0006-3223(02)01316-1</pub-id><pub-id pub-id-type=\"pmid\">12062886</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B30\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Lewis</surname><given-names>D.
        A.</given-names></name><name><surname>Lieberman</surname><given-names>J. A.</given-names></name></person-group>
        (<year>2000</year>). <article-title>Catching up on schizophrenia: natural
        history and neurobiology</article-title>. <source>Neuron</source>\n<volume>28</volume>,
        <fpage>325</fpage>&#x2013;<lpage>334</lpage><pub-id pub-id-type=\"doi\">10.1016/S0896-6273(00)00111-2</pub-id><pub-id
        pub-id-type=\"pmid\">11144342</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B31\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Liu</surname><given-names>B.</given-names></name><name><surname>Li</surname><given-names>J.</given-names></name><name><surname>Yu</surname><given-names>C.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Song</surname><given-names>M.</given-names></name><name><surname>Fan</surname><given-names>M.</given-names></name><name><surname>Li</surname><given-names>K.</given-names></name><name><surname>Jiang</surname><given-names>T.</given-names></name></person-group>
        (<year>2010</year>). <article-title>Haplotypes of catechol-O-methyltransferase
        modulate intelligence-related brain white matter integrity</article-title>.
        <source>Neuroimage</source>\n<volume>50</volume>, <fpage>243</fpage>&#x2013;<lpage>249</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.neuroimage.2009.12.020</pub-id><pub-id pub-id-type=\"pmid\">20005296</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B32\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Liu</surname><given-names>J.</given-names></name><name><surname>Pearlson</surname><given-names>G.</given-names></name><name><surname>Windemuth</surname><given-names>A.</given-names></name><name><surname>Ruano</surname><given-names>G.</given-names></name><name><surname>Perrone-Bizzozero</surname><given-names>N.
        I.</given-names></name><name><surname>Calhoun</surname><given-names>V.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Combining fMRI and SNP data to investigate
        connections between brain function and genetics using parallel ICA</article-title>.
        <source>Hum. Brain Mapp.</source>\n<volume>30</volume>, <fpage>241</fpage>&#x2013;<lpage>255</lpage><pub-id
        pub-id-type=\"doi\">10.1002/hbm.20508</pub-id><pub-id pub-id-type=\"pmid\">18072279</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B33\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>McIntosh</surname><given-names>A.
        M.</given-names></name><name><surname>Moorhead</surname><given-names>T. W.</given-names></name><name><surname>Job</surname><given-names>D.</given-names></name><name><surname>Lymer</surname><given-names>G.
        K.</given-names></name><name><surname>Munoz Maniega</surname><given-names>S.</given-names></name><name><surname>Mckirdy</surname><given-names>J.</given-names></name><name><surname>Sussmann</surname><given-names>J.
        E.</given-names></name><name><surname>Baig</surname><given-names>B. J.</given-names></name><name><surname>Bastin</surname><given-names>M.
        E.</given-names></name><name><surname>Porteous</surname><given-names>D.</given-names></name><name><surname>Evans</surname><given-names>K.
        L.</given-names></name><name><surname>Johnstone</surname><given-names>E. C.</given-names></name><name><surname>Lawrie</surname><given-names>S.
        M.</given-names></name><name><surname>Hall</surname><given-names>J.</given-names></name></person-group>
        (<year>2008</year>). <article-title>The effects of a neuregulin 1 variant
        on white matter density and integrity</article-title>. <source>Mol. Psychiatry</source>\n<volume>13</volume>,
        <fpage>1054</fpage>&#x2013;<lpage>1059</lpage><pub-id pub-id-type=\"doi\">10.1038/sj.mp.4002103</pub-id><pub-id
        pub-id-type=\"pmid\">17925794</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B34\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Meda</surname><given-names>S.
        A.</given-names></name><name><surname>Jagannathan</surname><given-names>K.</given-names></name><name><surname>Gelernter</surname><given-names>J.</given-names></name><name><surname>Calhoun</surname><given-names>V.
        D.</given-names></name><name><surname>Liu</surname><given-names>J.</given-names></name><name><surname>Stevens</surname><given-names>M.
        C.</given-names></name><name><surname>Pearlson</surname><given-names>G. D.</given-names></name></person-group>
        (<year>2010</year>). <article-title>A pilot multivariate parallel ICA study
        to investigate differential linkage between neural networks and genetic profiles
        in schizophrenia</article-title>. <source>Neuroimage</source>\n<volume>53</volume>,
        <fpage>1007</fpage>&#x2013;<lpage>1015</lpage><pub-id pub-id-type=\"doi\">10.1016/j.neuroimage.2009.11.052</pub-id><pub-id
        pub-id-type=\"pmid\">19944766</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B35\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Neural connectivity as an intermediate
        phenotype: brain networks under genetic control</article-title>. <source>Hum.
        Brain Mapp.</source>\n<volume>30</volume>, <fpage>1938</fpage>&#x2013;<lpage>1946</lpage><pub-id
        pub-id-type=\"doi\">10.1002/hbm.20639</pub-id><pub-id pub-id-type=\"pmid\">19294651</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B36\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2010</year>). <article-title>From maps to mechanisms through neuroimaging
        of schizophrenia</article-title>. <source>Nature</source>\n<volume>468</volume>,
        <fpage>194</fpage>&#x2013;<lpage>202</lpage><pub-id pub-id-type=\"doi\">10.1038/nature09569</pub-id><pub-id
        pub-id-type=\"pmid\">21068827</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B37\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name><name><surname>Poline</surname><given-names>J.
        B.</given-names></name><name><surname>Kohn</surname><given-names>P. D.</given-names></name><name><surname>Holt</surname><given-names>J.
        L.</given-names></name><name><surname>Egan</surname><given-names>M. F.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name><name><surname>Berman</surname><given-names>K. F.</given-names></name></person-group>
        (<year>2001</year>). <article-title>Evidence for abnormal cortical functional
        connectivity during working memory in schizophrenia</article-title>. <source>Am.
        J. Psychiatry</source>\n<volume>158</volume>, <fpage>1809</fpage>&#x2013;<lpage>1817</lpage><pub-id
        pub-id-type=\"doi\">10.1176/appi.ajp.158.11.1809</pub-id><pub-id pub-id-type=\"pmid\">11691686</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B38\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name><name><surname>Straub</surname><given-names>R.
        E.</given-names></name><name><surname>Lipska</surname><given-names>B. K.</given-names></name><name><surname>Verchinski</surname><given-names>B.
        A.</given-names></name><name><surname>Goldberg</surname><given-names>T.</given-names></name><name><surname>Callicott</surname><given-names>J.
        H.</given-names></name><name><surname>Egan</surname><given-names>M. F.</given-names></name><name><surname>Huffaker</surname><given-names>S.
        S.</given-names></name><name><surname>Mattay</surname><given-names>V. S.</given-names></name><name><surname>Kolachana</surname><given-names>B.</given-names></name><name><surname>Kleinman</surname><given-names>J.
        E.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name></person-group> (<year>2007</year>). <article-title>Genetic
        evidence implicating DARPP-32 in human frontostriatal structure, function,
        and cognition</article-title>. <source>J. Clin. Invest.</source>\n<volume>117</volume>,
        <fpage>672</fpage>&#x2013;<lpage>682</lpage><pub-id pub-id-type=\"doi\">10.1172/JCI30413</pub-id><pub-id
        pub-id-type=\"pmid\">17290303</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B39\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Meyer-Lindenberg</surname><given-names>A.
        S.</given-names></name><name><surname>Olsen</surname><given-names>R. K.</given-names></name><name><surname>Kohn</surname><given-names>P.
        D.</given-names></name><name><surname>Brown</surname><given-names>T.</given-names></name><name><surname>Egan</surname><given-names>M.
        F.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name><name><surname>Berman</surname><given-names>K. F.</given-names></name></person-group>
        (<year>2005</year>). <article-title>Regionally specific disturbance of dorsolateral
        prefrontal-hippocampal functional connectivity in schizophrenia</article-title>.
        <source>Arch. Gen. Psychiatry</source>\n<volume>62</volume>, <fpage>379</fpage>&#x2013;<lpage>386</lpage><pub-id
        pub-id-type=\"doi\">10.1001/archpsyc.62.4.379</pub-id><pub-id pub-id-type=\"pmid\">15809405</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B40\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Mier</surname><given-names>D.</given-names></name><name><surname>Kirsch</surname><given-names>P.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2010</year>). <article-title>Neural substrates of pleiotropic action
        of genetic variation in COMT: a meta-analysis</article-title>. <source>Mol.
        Psychiatry</source>\n<volume>15</volume>, <fpage>918</fpage>&#x2013;<lpage>927</lpage><pub-id
        pub-id-type=\"doi\">10.1038/mp.2009.36</pub-id><pub-id pub-id-type=\"pmid\">19417742</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B41\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Munafo</surname><given-names>M.
        R.</given-names></name><name><surname>Brown</surname><given-names>S. M.</given-names></name><name><surname>Hariri</surname><given-names>A.
        R.</given-names></name></person-group> (<year>2008</year>). <article-title>Serotonin
        transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis</article-title>.
        <source>Biol. Psychiatry</source>\n<volume>63</volume>, <fpage>852</fpage>&#x2013;<lpage>857</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.biopsych.2007.08.016</pub-id><pub-id pub-id-type=\"pmid\">17949693</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B42\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Nallasamy</surname><given-names>N.</given-names></name><name><surname>Tsao</surname><given-names>D.
        Y.</given-names></name></person-group> (<year>2011</year>). <article-title>Functional
        connectivity in the brain: effects of anesthesia</article-title>. <source>Neuroscientist.</source>\n<volume>17</volume>,
        <fpage>94</fpage>&#x2013;<lpage>106</lpage><pub-id pub-id-type=\"doi\">10.1177/1073858410374126</pub-id><pub-id
        pub-id-type=\"pmid\">21343409</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B43\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Nicodemus</surname><given-names>K.
        K.</given-names></name><name><surname>Law</surname><given-names>A. J.</given-names></name><name><surname>Radulescu</surname><given-names>E.</given-names></name><name><surname>Luna</surname><given-names>A.</given-names></name><name><surname>Kolachana</surname><given-names>B.</given-names></name><name><surname>Vakkalanka</surname><given-names>R.</given-names></name><name><surname>Rujescu</surname><given-names>D.</given-names></name><name><surname>Giegling</surname><given-names>I.</given-names></name><name><surname>Straub</surname><given-names>R.
        E.</given-names></name><name><surname>Mcgee</surname><given-names>K.</given-names></name><name><surname>Gold</surname><given-names>B.</given-names></name><name><surname>Dean</surname><given-names>M.</given-names></name><name><surname>Muglia</surname><given-names>P.</given-names></name><name><surname>Callicott</surname><given-names>J.
        H.</given-names></name><name><surname>Tan</surname><given-names>H. Y.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name></person-group> (<year>2010</year>). <article-title>Biological
        validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis
        via functional neuroimaging in healthy controls</article-title>. <source>Arch.
        Gen. Psychiatry</source>\n<volume>67</volume>, <fpage>991</fpage>&#x2013;<lpage>1001</lpage><pub-id
        pub-id-type=\"doi\">10.1001/archgenpsychiatry.2010.117</pub-id><pub-id pub-id-type=\"pmid\">20921115</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B44\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Norton</surname><given-names>N.</given-names></name><name><surname>Moskvina</surname><given-names>V.</given-names></name><name><surname>Morris</surname><given-names>D.
        W.</given-names></name><name><surname>Bray</surname><given-names>N. J.</given-names></name><name><surname>Zammit</surname><given-names>S.</given-names></name><name><surname>Williams</surname><given-names>N.
        M.</given-names></name><name><surname>Williams</surname><given-names>H. J.</given-names></name><name><surname>Preece</surname><given-names>A.
        C.</given-names></name><name><surname>Dwyer</surname><given-names>S.</given-names></name><name><surname>Wilkinson</surname><given-names>J.
        C.</given-names></name><name><surname>Spurlock</surname><given-names>G.</given-names></name><name><surname>Kirov</surname><given-names>G.</given-names></name><name><surname>Buckland</surname><given-names>P.</given-names></name><name><surname>Waddington</surname><given-names>J.
        L.</given-names></name><name><surname>Gill</surname><given-names>M.</given-names></name><name><surname>Corvin</surname><given-names>A.
        P.</given-names></name><name><surname>Owen</surname><given-names>M. J.</given-names></name><name><surname>O&#x2019;Donovan</surname><given-names>M.
        C.</given-names></name></person-group> (<year>2006</year>). <article-title>Evidence
        that interaction between neuregulin 1 and its receptor erbB4 increases susceptibility
        to schizophrenia</article-title>. <source>Am. J. Med. Genet. B Neuropsychiatr.
        Genet.</source>\n<volume>141B</volume>, <fpage>96</fpage>&#x2013;<lpage>101</lpage><pub-id
        pub-id-type=\"doi\">10.1002/ajmg.b.30236</pub-id><pub-id pub-id-type=\"pmid\">16249994</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B45\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>O&#x2019;Donovan</surname><given-names>M.
        C.</given-names></name><name><surname>Craddock</surname><given-names>N.</given-names></name><name><surname>Norton</surname><given-names>N.</given-names></name><name><surname>Williams</surname><given-names>H.</given-names></name><name><surname>Peirce</surname><given-names>T.</given-names></name><name><surname>Moskvina</surname><given-names>V.</given-names></name><name><surname>Nikolov</surname><given-names>I.</given-names></name><name><surname>Hamshere</surname><given-names>M.</given-names></name><name><surname>Carroll</surname><given-names>L.</given-names></name><name><surname>Georgieva</surname><given-names>L.</given-names></name><name><surname>Dwyer</surname><given-names>S.</given-names></name><name><surname>Holmans</surname><given-names>P.</given-names></name><name><surname>Marchini</surname><given-names>J.
        L.</given-names></name><name><surname>Spencer</surname><given-names>C. C.</given-names></name><name><surname>Howie</surname><given-names>B.</given-names></name><name><surname>Leung</surname><given-names>H.
        T.</given-names></name><name><surname>Hartmann</surname><given-names>A. M.</given-names></name><name><surname>Moller</surname><given-names>H.
        J.</given-names></name><name><surname>Morris</surname><given-names>D. W.</given-names></name><name><surname>Shi</surname><given-names>Y.</given-names></name><name><surname>Feng</surname><given-names>G.</given-names></name><name><surname>Hoffmann</surname><given-names>P.</given-names></name><name><surname>Propping</surname><given-names>P.</given-names></name><name><surname>Vasilescu</surname><given-names>C.</given-names></name><name><surname>Maier</surname><given-names>W.</given-names></name><name><surname>Rietschel</surname><given-names>M.</given-names></name><name><surname>Zammit</surname><given-names>S.</given-names></name><name><surname>Schumacher</surname><given-names>J.</given-names></name><name><surname>Quinn</surname><given-names>E.
        M.</given-names></name><name><surname>Schulze</surname><given-names>T. G.</given-names></name><name><surname>Williams</surname><given-names>N.
        M.</given-names></name><name><surname>Giegling</surname><given-names>I.</given-names></name><name><surname>Iwata</surname><given-names>N.</given-names></name><name><surname>Ikeda</surname><given-names>M.</given-names></name><name><surname>Darvasi</surname><given-names>A.</given-names></name><name><surname>Shifman</surname><given-names>S.</given-names></name><name><surname>He</surname><given-names>L.</given-names></name><name><surname>Duan</surname><given-names>J.</given-names></name><name><surname>Sanders</surname><given-names>A.
        R.</given-names></name><name><surname>Levinson</surname><given-names>D. F.</given-names></name><name><surname>Gejman</surname><given-names>P.
        V.</given-names></name><name><surname>Cichon</surname><given-names>S.</given-names></name><name><surname>Nothen</surname><given-names>M.
        M.</given-names></name><name><surname>Gill</surname><given-names>M.</given-names></name><name><surname>Corvin</surname><given-names>A.</given-names></name><name><surname>Rujescu</surname><given-names>D.</given-names></name><name><surname>Kirov</surname><given-names>G.</given-names></name><name><surname>Owen</surname><given-names>M.
        J.</given-names></name><name><surname>Buccola</surname><given-names>N. G.</given-names></name><name><surname>Mowry</surname><given-names>B.
        J.</given-names></name><name><surname>Freedman</surname><given-names>R.</given-names></name><name><surname>Amin</surname><given-names>F.</given-names></name><name><surname>Black</surname><given-names>D.
        W.</given-names></name><name><surname>Silverman</surname><given-names>J. M.</given-names></name><name><surname>Byerley</surname><given-names>W.
        F.</given-names></name><name><surname>Cloninger</surname><given-names>C. R.</given-names></name></person-group>
        (<year>2008</year>). <article-title>Identification of loci associated with
        schizophrenia by genome-wide association and follow-up</article-title>. <source>Nat.
        Genet.</source>\n<volume>40</volume>, <fpage>1053</fpage>&#x2013;<lpage>1055</lpage><pub-id
        pub-id-type=\"doi\">10.1038/ng.201</pub-id><pub-id pub-id-type=\"pmid\">18677311</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B46\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Ogawa</surname><given-names>S.</given-names></name><name><surname>Lee</surname><given-names>T.
        M.</given-names></name><name><surname>Kay</surname><given-names>A. R.</given-names></name><name><surname>Tank</surname><given-names>D.
        W.</given-names></name></person-group> (<year>1990</year>). <article-title>Brain
        magnetic resonance imaging with contrast dependent on blood oxygenation</article-title>.
        <source>Proc. Natl. Acad. Sci. U.S.A.</source>\n<volume>87</volume>, <fpage>9868</fpage>&#x2013;<lpage>9872</lpage><pub-id
        pub-id-type=\"doi\">10.1073/pnas.87.24.9868</pub-id><pub-id pub-id-type=\"pmid\">2124706</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B47\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Pacheco</surname><given-names>J.</given-names></name><name><surname>Beevers</surname><given-names>C.
        G.</given-names></name><name><surname>Benavides</surname><given-names>C.</given-names></name><name><surname>Mcgeary</surname><given-names>J.</given-names></name><name><surname>Stice</surname><given-names>E.</given-names></name><name><surname>Schnyer</surname><given-names>D.
        M.</given-names></name></person-group> (<year>2009</year>). <article-title>Frontal-limbic
        white matter pathway associations with the serotonin transporter gene promoter
        region (5-HTTLPR) polymorphism</article-title>. <source>J. Neurosci.</source>\n<volume>29</volume>,
        <fpage>6229</fpage>&#x2013;<lpage>6233</lpage><pub-id pub-id-type=\"doi\">10.1523/JNEUROSCI.0896-09.2009</pub-id><pub-id
        pub-id-type=\"pmid\">19439600</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B48\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Paulus</surname><given-names>F.
        M.</given-names></name><name><surname>Krach</surname><given-names>S.</given-names></name><name><surname>Bedenbender</surname><given-names>J.</given-names></name><name><surname>Pyka</surname><given-names>M.</given-names></name><name><surname>Sommer</surname><given-names>J.</given-names></name><name><surname>Krug</surname><given-names>A.</given-names></name><name><surname>Knake</surname><given-names>S.</given-names></name><name><surname>Nothen</surname><given-names>M.
        M.</given-names></name><name><surname>Witt</surname><given-names>S. H.</given-names></name><name><surname>Rietschel</surname><given-names>M.</given-names></name><name><surname>Kircher</surname><given-names>T.</given-names></name><name><surname>Jansen</surname><given-names>A.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Partial support for ZNF804A genotype-dependent
        alterations in prefrontal connectivity</article-title>. <source>Hum. Brain
        Mapp</source>.<pub-id pub-id-type=\"doi\">10.1002/hbm.21434</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B49\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Perez-Iglesias</surname><given-names>R.</given-names></name><name><surname>Tordesillas-Gutierrez</surname><given-names>D.</given-names></name><name><surname>Barker</surname><given-names>G.
        J.</given-names></name><name><surname>Mcguire</surname><given-names>P. K.</given-names></name><name><surname>Roiz-Santianez</surname><given-names>R.</given-names></name><name><surname>Mata</surname><given-names>I.</given-names></name><name><surname>De
        Lucas</surname><given-names>E. M.</given-names></name><name><surname>Quintana</surname><given-names>F.</given-names></name><name><surname>Vazquez-Barquero</surname><given-names>J.
        L.</given-names></name><name><surname>Crespo-Facorro</surname><given-names>B.</given-names></name></person-group>
        (<year>2010</year>). <article-title>White matter defects in first episode
        psychosis patients: a voxelwise analysis of diffusion tensor imaging</article-title>.
        <source>Neuroimage</source>\n<volume>49</volume>, <fpage>199</fpage>&#x2013;<lpage>204</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.neuroimage.2009.07.016</pub-id><pub-id pub-id-type=\"pmid\">19619664</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B50\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Pezawas</surname><given-names>L.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name><name><surname>Drabant</surname><given-names>E.
        M.</given-names></name><name><surname>Verchinski</surname><given-names>B.
        A.</given-names></name><name><surname>Munoz</surname><given-names>K. E.</given-names></name><name><surname>Kolachana</surname><given-names>B.
        S.</given-names></name><name><surname>Egan</surname><given-names>M. F.</given-names></name><name><surname>Mattay</surname><given-names>V.
        S.</given-names></name><name><surname>Hariri</surname><given-names>A. R.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name></person-group> (<year>2005</year>). <article-title>5-HTTLPR
        polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility
        mechanism for depression</article-title>. <source>Nat. Neurosci.</source>\n<volume>8</volume>,
        <fpage>828</fpage>&#x2013;<lpage>834</lpage><pub-id pub-id-type=\"doi\">10.1038/nn1463</pub-id><pub-id
        pub-id-type=\"pmid\">15880108</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B51\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Pitt</surname><given-names>D.</given-names></name><name><surname>Nagelmeier</surname><given-names>I.
        E.</given-names></name><name><surname>Wilson</surname><given-names>H. C.</given-names></name><name><surname>Raine</surname><given-names>C.
        S.</given-names></name></person-group> (<year>2003</year>). <article-title>Glutamate
        uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis</article-title>.
        <source>Neurology</source>\n<volume>61</volume>, <fpage>1113</fpage>&#x2013;<lpage>1120</lpage><pub-id
        pub-id-type=\"pmid\">14581674</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B52\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Prata</surname><given-names>D.
        P.</given-names></name><name><surname>Mechelli</surname><given-names>A.</given-names></name><name><surname>Fu</surname><given-names>C.
        H.</given-names></name><name><surname>Picchioni</surname><given-names>M.</given-names></name><name><surname>Kane</surname><given-names>F.</given-names></name><name><surname>Kalidindi</surname><given-names>S.</given-names></name><name><surname>Mcdonald</surname><given-names>C.</given-names></name><name><surname>Howes</surname><given-names>O.</given-names></name><name><surname>Kravariti</surname><given-names>E.</given-names></name><name><surname>Demjaha</surname><given-names>A.</given-names></name><name><surname>Toulopoulou</surname><given-names>T.</given-names></name><name><surname>Diforti</surname><given-names>M.</given-names></name><name><surname>Murray</surname><given-names>R.
        M.</given-names></name><name><surname>Collier</surname><given-names>D. A.</given-names></name><name><surname>Mcguire</surname><given-names>P.
        K.</given-names></name></person-group> (<year>2009</year>). <article-title>Opposite
        effects of catechol-O-methyltransferase Val158Met on cortical function in
        healthy subjects and patients with schizophrenia</article-title>. <source>Biol.
        Psychiatry</source>\n<volume>65</volume>, <fpage>473</fpage>&#x2013;<lpage>480</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.biopsych.2008.09.027</pub-id><pub-id pub-id-type=\"pmid\">19054502</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B53\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Rao</surname><given-names>D.</given-names></name><name><surname>Jonsson</surname><given-names>E.
        G.</given-names></name><name><surname>Paus</surname><given-names>S.</given-names></name><name><surname>Ganguli</surname><given-names>R.</given-names></name><name><surname>Nothen</surname><given-names>M.</given-names></name><name><surname>Nimgaonkar</surname><given-names>V.
        L.</given-names></name></person-group> (<year>1998</year>). <article-title>Schizophrenia
        and the serotonin transporter gene</article-title>. <source>Psychiatr. Genet.</source>\n<volume>8</volume>,
        <fpage>207</fpage>&#x2013;<lpage>212</lpage><pub-id pub-id-type=\"doi\">10.1097/00041444-199808040-00002</pub-id><pub-id
        pub-id-type=\"pmid\">9861638</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B54\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Rasetti</surname><given-names>R.</given-names></name><name><surname>Sambataro</surname><given-names>F.</given-names></name><name><surname>Chen</surname><given-names>Q.</given-names></name><name><surname>Callicott</surname><given-names>J.
        H.</given-names></name><name><surname>Mattay</surname><given-names>V. S.</given-names></name><name><surname>Weinberger</surname><given-names>D.
        R.</given-names></name></person-group> (<year>2011</year>). <article-title>Altered
        Cortical Network Dynamics: A Potential Intermediate Phenotype for Schizophrenia
        and Association With ZNF804A</article-title>. <source>Arch. Gen. Psychiatry</source>\n<volume>68</volume>,
        <fpage>1207</fpage>&#x2013;<lpage>1217</lpage><pub-id pub-id-type=\"doi\">10.1001/archgenpsychiatry.2011.103</pub-id><pub-id
        pub-id-type=\"pmid\">21810628</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B55\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Roffman</surname><given-names>J.
        L.</given-names></name><name><surname>Brohawn</surname><given-names>D. G.</given-names></name><name><surname>Friedman</surname><given-names>J.
        S.</given-names></name><name><surname>Dyckman</surname><given-names>K. A.</given-names></name><name><surname>Thakkar</surname><given-names>K.
        N.</given-names></name><name><surname>Agam</surname><given-names>Y.</given-names></name><name><surname>Vangel</surname><given-names>M.
        G.</given-names></name><name><surname>Goff</surname><given-names>D. C.</given-names></name><name><surname>Manoach</surname><given-names>D.
        S.</given-names></name></person-group> (<year>2011</year>). <article-title>MTHFR
        677C&gt;T effects on anterior cingulate structure and function during response
        monitoring in schizophrenia: a preliminary study</article-title>. <source>Brain
        Imaging Behav.</source>\n<volume>5</volume>, <fpage>65</fpage>&#x2013;<lpage>75</lpage><pub-id
        pub-id-type=\"doi\">10.1007/s11682-010-9111-2</pub-id><pub-id pub-id-type=\"pmid\">21190096</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B56\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Roffman</surname><given-names>J.
        L.</given-names></name><name><surname>Weiss</surname><given-names>A. P.</given-names></name><name><surname>Purcell</surname><given-names>S.</given-names></name><name><surname>Caffalette</surname><given-names>C.
        A.</given-names></name><name><surname>Freudenreich</surname><given-names>O.</given-names></name><name><surname>Henderson</surname><given-names>D.
        C.</given-names></name><name><surname>Bottiglieri</surname><given-names>T.</given-names></name><name><surname>Wong</surname><given-names>D.
        H.</given-names></name><name><surname>Halsted</surname><given-names>C. H.</given-names></name><name><surname>Goff</surname><given-names>D.
        C.</given-names></name></person-group> (<year>2008</year>). <article-title>Contribution
        of methylenetetrahydrofolate reductase (MTHFR) polymorphisms to negative symptoms
        in schizophrenia</article-title>. <source>Biol. Psychiatry</source>\n<volume>63</volume>,
        <fpage>42</fpage>&#x2013;<lpage>48</lpage><pub-id pub-id-type=\"doi\">10.1016/j.biopsych.2006.12.017</pub-id><pub-id
        pub-id-type=\"pmid\">17543893</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B57\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Schumann</surname><given-names>G.</given-names></name><name><surname>Loth</surname><given-names>E.</given-names></name><name><surname>Banaschewski</surname><given-names>T.</given-names></name><name><surname>Barbot</surname><given-names>A.</given-names></name><name><surname>Barker</surname><given-names>G.</given-names></name><name><surname>Buchel</surname><given-names>C.</given-names></name><name><surname>Conrod</surname><given-names>P.
        J.</given-names></name><name><surname>Dalley</surname><given-names>J. W.</given-names></name><name><surname>Flor</surname><given-names>H.</given-names></name><name><surname>Gallinat</surname><given-names>J.</given-names></name><name><surname>Garavan</surname><given-names>H.</given-names></name><name><surname>Heinz</surname><given-names>A.</given-names></name><name><surname>Itterman</surname><given-names>B.</given-names></name><name><surname>Lathrop</surname><given-names>M.</given-names></name><name><surname>Mallik</surname><given-names>C.</given-names></name><name><surname>Mann</surname><given-names>K.</given-names></name><name><surname>Martinot</surname><given-names>J.
        L.</given-names></name><name><surname>Paus</surname><given-names>T.</given-names></name><name><surname>Poline</surname><given-names>J.
        B.</given-names></name><name><surname>Robbins</surname><given-names>T. W.</given-names></name><name><surname>Rietschel</surname><given-names>M.</given-names></name><name><surname>Reed</surname><given-names>L.</given-names></name><name><surname>Smolka</surname><given-names>M.</given-names></name><name><surname>Spanagel</surname><given-names>R.</given-names></name><name><surname>Speiser</surname><given-names>C.</given-names></name><name><surname>Stephens</surname><given-names>D.
        N.</given-names></name><name><surname>Strohle</surname><given-names>A.</given-names></name><name><surname>Struve</surname><given-names>M.</given-names></name></person-group>
        (<year>2010</year>). <article-title>The IMAGEN study: reinforcement-related
        behaviour in normal brain function and psychopathology</article-title>. <source>Mol.
        Psychiatry</source>\n<volume>15</volume>, <fpage>1128</fpage>&#x2013;<lpage>1139</lpage><pub-id
        pub-id-type=\"doi\">10.1038/mp.2010.4</pub-id><pub-id pub-id-type=\"pmid\">21102431</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B58\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Selemon</surname><given-names>L.
        D.</given-names></name><name><surname>Goldman-Rakic</surname><given-names>P.
        S.</given-names></name></person-group> (<year>1999</year>). <article-title>The
        reduced neuropil hypothesis: a circuit based model of schizophrenia</article-title>.
        <source>Biol. Psychiatry</source>\n<volume>45</volume>, <fpage>17</fpage>&#x2013;<lpage>25</lpage><pub-id
        pub-id-type=\"doi\">10.1016/S0006-3223(98)00281-9</pub-id><pub-id pub-id-type=\"pmid\">9894571</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B59\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Sigurdsson</surname><given-names>T.</given-names></name><name><surname>Stark</surname><given-names>K.
        L.</given-names></name><name><surname>Karayiorgou</surname><given-names>M.</given-names></name><name><surname>Gogos</surname><given-names>J.
        A.</given-names></name><name><surname>Gordon</surname><given-names>J. A.</given-names></name></person-group>
        (<year>2010</year>). <article-title>Impaired hippocampal&#x2013;prefrontal
        synchrony in a genetic mouse model of schizophrenia</article-title>. <source>Nature</source>\n<volume>464</volume>,
        <fpage>763</fpage><pub-id pub-id-type=\"doi\">10.1038/nature08855</pub-id><pub-id
        pub-id-type=\"pmid\">20360742</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B60\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Sprooten</surname><given-names>E.</given-names></name><name><surname>Lymer</surname><given-names>G.
        K.</given-names></name><name><surname>Munoz Maniega</surname><given-names>S.</given-names></name><name><surname>Mckirdy</surname><given-names>J.</given-names></name><name><surname>Clayden</surname><given-names>J.
        D.</given-names></name><name><surname>Bastin</surname><given-names>M. E.</given-names></name><name><surname>Porteous</surname><given-names>D.</given-names></name><name><surname>Johnstone</surname><given-names>E.
        C.</given-names></name><name><surname>Lawrie</surname><given-names>S. M.</given-names></name><name><surname>Hall</surname><given-names>J.</given-names></name><name><surname>Mcintosh</surname><given-names>A.
        M.</given-names></name></person-group> (<year>2009</year>). <article-title>The
        relationship of anterior thalamic radiation integrity to psychosis risk associated
        neuregulin-1 variants</article-title>. <source>Mol. Psychiatry</source>\n<volume>14</volume>,
        <fpage>237</fpage>&#x2013;<lpage>238</lpage>, 233.<pub-id pub-id-type=\"doi\">10.1038/mp.2009.1</pub-id><pub-id
        pub-id-type=\"pmid\">19229203</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B61\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Sprooten</surname><given-names>E.</given-names></name><name><surname>Sussman</surname><given-names>J.
        E.</given-names></name><name><surname>Moorhear</surname><given-names>T. W.</given-names></name><name><surname>Whalley</surname><given-names>H.
        C.</given-names></name><name><surname>ffrench-Constant</surname><given-names>C.</given-names></name><name><surname>Blumberg</surname><given-names>H.
        P.</given-names></name><name><surname>Bastin</surname><given-names>M. E.</given-names></name><name><surname>Hall</surname><given-names>J.</given-names></name><name><surname>Lawrie</surname><given-names>S.
        M.</given-names></name><name><surname>McIntosh</surname><given-names>A. M.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Association of white matter imtegrity
        with genetic variation in an exonic DISC1 SNP</article-title>. <source>Mol.
        Psychiatry</source>\n<fpage>1</fpage>&#x2013;<lpage>2</lpage><pub-id pub-id-type=\"pmid\">21483438</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B62\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Stephan</surname><given-names>K.
        E.</given-names></name><name><surname>Friston</surname><given-names>K. J.</given-names></name><name><surname>Frith</surname><given-names>C.
        D.</given-names></name></person-group> (<year>2009</year>). <article-title>Dysconnection
        in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring</article-title>.
        <source>Schizophr. Bull.</source>\n<volume>35</volume>, <fpage>509</fpage>&#x2013;<lpage>527</lpage><pub-id
        pub-id-type=\"doi\">10.1093/schbul/sbn176</pub-id><pub-id pub-id-type=\"pmid\">19155345</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B63\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Sterne</surname><given-names>J.
        A.</given-names></name><name><surname>Gavaghan</surname><given-names>D.</given-names></name><name><surname>Egger</surname><given-names>M.</given-names></name></person-group>
        (<year>2000</year>). <article-title>Publication and related bias in meta-analysis:
        power of statistical tests and prevalence in the literature</article-title>.
        <source>J. Clin. Epidemiol.</source>\n<volume>53</volume>, <fpage>1119</fpage>&#x2013;<lpage>1129</lpage><pub-id
        pub-id-type=\"doi\">10.1016/S0895-4356(00)00242-0</pub-id><pub-id pub-id-type=\"pmid\">11106885</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B64\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Sullivan</surname><given-names>P.
        F.</given-names></name><name><surname>Kendler</surname><given-names>K. S.</given-names></name><name><surname>Neale</surname><given-names>M.
        C.</given-names></name></person-group> (<year>2003</year>). <article-title>Schizophrenia
        as a complex trait: evidence from a meta-analysis of twin studies</article-title>.
        <source>Arch. Gen. Psychiatry</source>\n<volume>60</volume>, <fpage>1187</fpage>&#x2013;<lpage>1192</lpage><pub-id
        pub-id-type=\"doi\">10.1001/archpsyc.60.12.1187</pub-id><pub-id pub-id-type=\"pmid\">14662550</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B65\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Takahashi</surname><given-names>N.</given-names></name><name><surname>Sakurai</surname><given-names>T.</given-names></name><name><surname>Davis</surname><given-names>K.
        L.</given-names></name><name><surname>Buxbaum</surname><given-names>J. D.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Linking oligodendrocyte and myelin dysfunction
        to neurocircuitry abnormalities in schizophrenia</article-title>. <source>Prog.
        Neurobiol.</source>\n<volume>93</volume>, <fpage>13</fpage>&#x2013;<lpage>24</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.pneurobio.2010.09.004</pub-id><pub-id pub-id-type=\"pmid\">20950668</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B66\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Tanaka</surname><given-names>H.</given-names></name><name><surname>Ma</surname><given-names>J.</given-names></name><name><surname>Tanaka</surname><given-names>K.
        F.</given-names></name><name><surname>Takao</surname><given-names>K.</given-names></name><name><surname>Komada</surname><given-names>M.</given-names></name><name><surname>Tanda</surname><given-names>K.</given-names></name><name><surname>Suzuki</surname><given-names>A.</given-names></name><name><surname>Ishibashi</surname><given-names>T.</given-names></name><name><surname>Baba</surname><given-names>H.</given-names></name><name><surname>Isa</surname><given-names>T.</given-names></name><name><surname>Shigemoto</surname><given-names>R.</given-names></name><name><surname>Ono</surname><given-names>K.</given-names></name><name><surname>Miyakawa</surname><given-names>T.</given-names></name><name><surname>Ikenaka</surname><given-names>K.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Mice with altered myelin proteolipid protein
        gene expression display cognitive deficits accompanied by abnormal neuron-glia
        interactions and decreased conduction velocities</article-title>. <source>J.
        Neurosci.</source>\n<volume>29</volume>, <fpage>8363</fpage>&#x2013;<lpage>8371</lpage><pub-id
        pub-id-type=\"doi\">10.1523/JNEUROSCI.2799-09.2009</pub-id><pub-id pub-id-type=\"pmid\">19571127</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B67\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Thomason</surname><given-names>M.
        E.</given-names></name><name><surname>Dougherty</surname><given-names>R. F.</given-names></name><name><surname>Colich</surname><given-names>N.
        L.</given-names></name><name><surname>Perry</surname><given-names>L. M.</given-names></name><name><surname>Rykhlevskaia</surname><given-names>E.
        I.</given-names></name><name><surname>Louro</surname><given-names>H. M.</given-names></name><name><surname>Hallmayer</surname><given-names>J.
        F.</given-names></name><name><surname>Waugh</surname><given-names>C. E.</given-names></name><name><surname>Bammer</surname><given-names>R.</given-names></name><name><surname>Glover</surname><given-names>G.
        H.</given-names></name><name><surname>Gotlib</surname><given-names>I. H.</given-names></name></person-group>
        (<year>2010</year>). <article-title>COMT genotype affects prefrontal white
        matter pathways in children and adolescents</article-title>. <source>Neuroimage</source>\n<volume>53</volume>,
        <fpage>926</fpage>&#x2013;<lpage>934</lpage><pub-id pub-id-type=\"doi\">10.1016/j.neuroimage.2010.01.033</pub-id><pub-id
        pub-id-type=\"pmid\">20083203</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B68\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Tost</surname><given-names>H.</given-names></name><name><surname>Bilek</surname><given-names>E.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Brain connectivity in psychiatric imaging
        genetics</article-title>. <source>Neuroimage</source>.<pub-id pub-id-type=\"doi\">10.1016/j.neuroimage.2011.11.007</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B69\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Tournier</surname><given-names>J.
        D.</given-names></name><name><surname>Mori</surname><given-names>S.</given-names></name><name><surname>Leemans</surname><given-names>A.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Diffusion tensor imaging and beyond</article-title>.
        <source>Magn. Reson. Med.</source>\n<volume>65</volume>, <fpage>1532</fpage>&#x2013;<lpage>1556</lpage><pub-id
        pub-id-type=\"doi\">10.1002/mrm.22924</pub-id><pub-id pub-id-type=\"pmid\">21469191</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B70\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Umbricht</surname><given-names>D.</given-names></name><name><surname>Schmid</surname><given-names>L.</given-names></name><name><surname>Koller</surname><given-names>R.</given-names></name><name><surname>Vollenweider</surname><given-names>F.
        X.</given-names></name><name><surname>Hell</surname><given-names>D.</given-names></name><name><surname>Javitt</surname><given-names>D.
        C.</given-names></name></person-group> (<year>2000</year>). <article-title>Ketamine-induced
        deficits in auditory and visual context-dependent processing in healthy volunteers:
        implications for models of cognitive deficits in schizophrenia</article-title>.
        <source>Arch. Gen. Psychiatry</source>\n<volume>57</volume>, <fpage>1139</fpage>&#x2013;<lpage>1147</lpage><pub-id
        pub-id-type=\"doi\">10.1001/archpsyc.57.12.1139</pub-id><pub-id pub-id-type=\"pmid\">11115327</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B71\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Vijayan</surname><given-names>N.
        N.</given-names></name><name><surname>Iwayama</surname><given-names>Y.</given-names></name><name><surname>Koshy</surname><given-names>L.
        V.</given-names></name><name><surname>Natarajan</surname><given-names>C.</given-names></name><name><surname>Nair</surname><given-names>C.</given-names></name><name><surname>Allencherry</surname><given-names>P.
        M.</given-names></name><name><surname>Yoshikawa</surname><given-names>T.</given-names></name><name><surname>Banerjee</surname><given-names>M.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Evidence of association of serotonin transporter
        gene polymorphisms with schizophrenia in a South Indian population</article-title>.
        <source>J. Hum. Genet.</source>\n<volume>54</volume>, <fpage>538</fpage>&#x2013;<lpage>542</lpage><pub-id
        pub-id-type=\"doi\">10.1038/jhg.2009.76</pub-id><pub-id pub-id-type=\"pmid\">19713975</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B72\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Walter</surname><given-names>H.</given-names></name><name><surname>Schnell</surname><given-names>K.</given-names></name><name><surname>Erk</surname><given-names>S.</given-names></name><name><surname>Arnold</surname><given-names>C.</given-names></name><name><surname>Kirsch</surname><given-names>P.</given-names></name><name><surname>Esslinger</surname><given-names>C.</given-names></name><name><surname>Mier</surname><given-names>D.</given-names></name><name><surname>Schmitgen</surname><given-names>M.
        M.</given-names></name><name><surname>Rietschel</surname><given-names>M.</given-names></name><name><surname>Witt</surname><given-names>S.
        H.</given-names></name><name><surname>Nothen</surname><given-names>M. M.</given-names></name><name><surname>Cichon</surname><given-names>S.</given-names></name><name><surname>Meyer-Lindenberg</surname><given-names>A.</given-names></name></person-group>
        (<year>2011</year>). <article-title>Effects of a genome-wide supported psychosis
        risk variant on neural activation during a theory-of-mind task</article-title>.
        <source>Mol. Psychiatry</source>\n<volume>16</volume>, <fpage>462</fpage>&#x2013;<lpage>470</lpage><pub-id
        pub-id-type=\"doi\">10.1038/mp.2010.18</pub-id><pub-id pub-id-type=\"pmid\">20231838</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B73\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Wang</surname><given-names>F.</given-names></name><name><surname>Jiang</surname><given-names>T.</given-names></name><name><surname>Sun</surname><given-names>Z.</given-names></name><name><surname>Teng</surname><given-names>S.
        L.</given-names></name><name><surname>Luo</surname><given-names>X.</given-names></name><name><surname>Zhu</surname><given-names>Z.</given-names></name><name><surname>Zang</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>H.</given-names></name><name><surname>Yue</surname><given-names>W.</given-names></name><name><surname>Qu</surname><given-names>M.</given-names></name><name><surname>Lu</surname><given-names>T.</given-names></name><name><surname>Hong</surname><given-names>N.</given-names></name><name><surname>Huang</surname><given-names>H.</given-names></name><name><surname>Blumberg</surname><given-names>H.
        P.</given-names></name><name><surname>Zhang</surname><given-names>D.</given-names></name></person-group>
        (<year>2009</year>). <article-title>Neuregulin 1 genetic variation and anterior
        cingulum integrity in patients with schizophrenia and healthy controls</article-title>.
        <source>J Psychiatry Neurosci</source>\n<volume>34</volume>, <fpage>181</fpage>&#x2013;<lpage>186</lpage><pub-id
        pub-id-type=\"pmid\">19448847</pub-id></mixed-citation>\n      </ref>\n      <ref
        id=\"B74\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Winterer</surname><given-names>G.</given-names></name><name><surname>Konrad</surname><given-names>A.</given-names></name><name><surname>Vucurevic</surname><given-names>G.</given-names></name><name><surname>Musso</surname><given-names>F.</given-names></name><name><surname>Stoeter</surname><given-names>P.</given-names></name><name><surname>Dahmen</surname><given-names>N.</given-names></name></person-group>
        (<year>2008</year>). <article-title>Association of 5&#x2032; end neuregulin-1
        (NRG1) gene variation with subcortical medial frontal microstructure in humans</article-title>.
        <source>Neuroimage</source>\n<volume>40</volume>, <fpage>712</fpage>&#x2013;<lpage>718</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.neuroimage.2007.12.041</pub-id><pub-id pub-id-type=\"pmid\">18255317</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B75\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Witthaus</surname><given-names>H.</given-names></name><name><surname>Brune</surname><given-names>M.</given-names></name><name><surname>Kaufmann</surname><given-names>C.</given-names></name><name><surname>Bohner</surname><given-names>G.</given-names></name><name><surname>Ozgurdal</surname><given-names>S.</given-names></name><name><surname>Gudlowski</surname><given-names>Y.</given-names></name><name><surname>Heinz</surname><given-names>A.</given-names></name><name><surname>Klingebiel</surname><given-names>R.</given-names></name><name><surname>Juckel</surname><given-names>G.</given-names></name></person-group>
        (<year>2008</year>). <article-title>White matter abnormalities in subjects
        at ultra high-risk for schizophrenia and first-episode schizophrenic patients</article-title>.
        <source>Schizophr. Res.</source>\n<volume>102</volume>, <fpage>141</fpage>&#x2013;<lpage>149</lpage><pub-id
        pub-id-type=\"doi\">10.1016/S0920-9964(08)70427-4</pub-id><pub-id pub-id-type=\"pmid\">18515047</pub-id></mixed-citation>\n
        \     </ref>\n      <ref id=\"B76\">\n        <mixed-citation publication-type=\"journal\"><person-group
        person-group-type=\"author\"><name><surname>Zuliani</surname><given-names>R.</given-names></name><name><surname>Moorhead</surname><given-names>T.
        W.</given-names></name><name><surname>Bastin</surname><given-names>M. E.</given-names></name><name><surname>Johnstone</surname><given-names>E.
        C.</given-names></name><name><surname>Lawrie</surname><given-names>S. M.</given-names></name><name><surname>Brambilla</surname><given-names>P.</given-names></name><name><surname>O&#x2019;Donovan</surname><given-names>M.
        C.</given-names></name><name><surname>Owen</surname><given-names>M. J.</given-names></name><name><surname>Hall</surname><given-names>J.</given-names></name><name><surname>Mcintosh</surname><given-names>A.
        M.</given-names></name></person-group> (<year>2011</year>). <article-title>Genetic
        variants in the ErbB4 gene are associated with white matter integrity</article-title>.
        <source>Psychiatry Res.</source>\n<volume>191</volume>, <fpage>133</fpage>&#x2013;<lpage>137</lpage><pub-id
        pub-id-type=\"doi\">10.1016/j.pscychresns.2010.11.001</pub-id><pub-id pub-id-type=\"pmid\">21232925</pub-id></mixed-citation>\n
        \     </ref>\n    </ref-list>\n  </back>\n</article>\n</pmc-articleset>"
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