{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:23:23Z","timestamp":1778563403128,"version":"3.51.4"},"reference-count":63,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2007,5,10]],"date-time":"2007-05-10T00:00:00Z","timestamp":1178755200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:sec id=\"S0033291707000700_sec_a001\"><jats:title>Background<\/jats:title><jats:p>Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (<jats:italic>Val<\/jats:italic><jats:sup><jats:italic>158<\/jats:italic><\/jats:sup><jats:italic>Met<\/jats:italic>) affecting enzyme activity. Here, we investigated the effect of COMT <jats:italic>Val<\/jats:italic><jats:sup><jats:italic>158<\/jats:italic><\/jats:sup><jats:italic>Met<\/jats:italic> polymorphism on brain anatomy and cognition in adults with VCFS.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291707000700_sec_a002\"><jats:title>Method<\/jats:title><jats:p>The COMT <jats:italic>Val<\/jats:italic><jats:sup><jats:italic>158<\/jats:italic><\/jats:sup><jats:italic>Met<\/jats:italic> polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291707000700_sec_a003\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>After corrections for multiple comparisons <jats:italic>Val<\/jats:italic>-hemizygous subjects, compared with <jats:italic>Met<\/jats:italic>-hemizygotes, had a significantly larger volume of frontal lobes. Also, <jats:italic>Val<\/jats:italic>-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found.<\/jats:p><\/jats:sec><jats:sec id=\"S0033291707000700_sec_a004\" sec-type=\"conclusion\"><jats:title>Conclusions<\/jats:title><jats:p>COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0033291707000700","type":"journal-article","created":{"date-parts":[[2007,5,10]],"date-time":"2007-05-10T08:53:44Z","timestamp":1178787224000},"page":"89-100","source":"Crossref","is-referenced-by-count":34,"title":["Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome"],"prefix":"10.1017","volume":"38","author":[{"given":"T.","family":"van Amelsvoort","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Zinkstok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Figee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.\u00a0J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.\u00a0C.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"De Haan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.\u00a0H.","family":"Linszen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Glaser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.\u00a0G.\u00a0M.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2007,5,10]]},"reference":[{"key":"S0033291707000700_ref054","doi-asserted-by":"publisher","DOI":"10.1016\/S0730-725X(99)00055-7"},{"key":"S0033291707000700_ref002","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005038"},{"key":"S0033291707000700_ref034","first-page":"247","volume-title":"Lines of Thinking","author":"Morris","year":"1990"},{"key":"S0033291707000700_ref055","volume-title":"Co-Planar Stereotaxic Atlas of the Human Brain","author":"Talairach","year":"1988"},{"key":"S0033291707000700_ref047","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00569.x"},{"key":"S0033291707000700_ref039","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.10.940"},{"key":"S0033291707000700_ref009","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.9.1700"},{"key":"S0033291707000700_ref033","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320540204"},{"key":"S0033291707000700_ref036","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(93)90153-5"},{"key":"S0033291707000700_ref042","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1176\/ajp.153.12.1541","article-title":"Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder?","volume":"153","author":"Papolos","year":"1996","journal-title":"American Journal of Psychiatry"},{"key":"S0033291707000700_ref020","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.3.537"},{"key":"S0033291707000700_ref015","doi-asserted-by":"publisher","DOI":"10.1086\/425589"},{"key":"S0033291707000700_ref001","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1523\/JNEUROSCI.23-06-02008.2003","article-title":"Catechol-O-methyltransferase genotype and dopamine regulation in the human brain","volume":"23","author":"Akil","year":"2003","journal-title":"Journal of Neuroscience"},{"key":"S0033291707000700_ref012","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1995.1016"},{"key":"S0033291707000700_ref035","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.6.757"},{"key":"S0033291707000700_ref027","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)01002-7"},{"key":"S0033291707000700_ref013","doi-asserted-by":"publisher","DOI":"10.1109\/42.750253"},{"key":"S0033291707000700_ref010","volume-title":"Multilingual Aphasia Examination","author":"Benton","year":"1976"},{"key":"S0033291707000700_ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.07.038"},{"key":"S0033291707000700_ref037","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)92184-U"},{"key":"S0033291707000700_ref043","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/1.2.140"},{"key":"S0033291707000700_ref016","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00150-X"},{"key":"S0033291707000700_ref006","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3932(95)00133-6"},{"key":"S0033291707000700_ref007","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(97)00049-6"},{"key":"S0033291707000700_ref038","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1992.00530320063013"},{"key":"S0033291707000700_ref026","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30284"},{"key":"S0033291707000700_ref032","doi-asserted-by":"publisher","DOI":"10.1038\/nn1438"},{"key":"S0033291707000700_ref056","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.10.024"},{"key":"S0033291707000700_ref049","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.2.234"},{"key":"S0033291707000700_ref003","volume-title":"Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV)","year":"1994"},{"key":"S0033291707000700_ref024","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001616"},{"key":"S0033291707000700_ref014","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl066"},{"key":"S0033291707000700_ref051","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1792-04.2005"},{"key":"S0033291707000700_ref057","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.61.11.1085"},{"key":"S0033291707000700_ref048","first-page":"56","article-title":"A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome","volume":"15","author":"Shprintzen","year":"1978","journal-title":"Cleft Palate Journal"},{"key":"S0033291707000700_ref052","doi-asserted-by":"publisher","DOI":"10.1038\/13154"},{"key":"S0033291707000700_ref022","doi-asserted-by":"publisher","DOI":"10.1038\/nn1572"},{"key":"S0033291707000700_ref029","doi-asserted-by":"publisher","DOI":"10.1007\/s002210000397"},{"key":"S0033291707000700_ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.03.020"},{"key":"S0033291707000700_ref040","doi-asserted-by":"publisher","DOI":"10.1162\/0898929041920441"},{"key":"S0033291707000700_ref058","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.178.5.412"},{"key":"S0033291707000700_ref004","volume-title":"The Doors and People Test: a Test of Visual and Verbal Recall and Recognition","author":"Baddeley","year":"1994"},{"key":"S0033291707000700_ref060","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.05.045"},{"key":"S0033291707000700_ref044","volume-title":"Numerical Recipes in C: The Art of Scientific Computing","author":"Press","year":"1992"},{"key":"S0033291707000700_ref017","volume-title":"Continuous Performance Test","author":"Conner","year":"1995"},{"key":"S0033291707000700_ref041","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(02)00011-4"},{"key":"S0033291707000700_ref063","volume-title":"Wechsler Memory Scale\u00a0\u2013\u00a0Revised: Manual","author":"Wechsler","year":"1987"},{"key":"S0033291707000700_ref023","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.3.410"},{"key":"S0033291707000700_ref064","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1990.01810180089012"},{"key":"S0033291707000700_ref061","volume-title":"The Visual Object and Space Perception Battery","author":"Warrington","year":"1991"},{"key":"S0033291707000700_ref050","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.11.018"},{"key":"S0033291707000700_ref011","doi-asserted-by":"publisher","DOI":"10.1016\/S0730-725X(97)00135-5"},{"key":"S0033291707000700_ref018","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92553-R"},{"key":"S0033291707000700_ref028","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199606000-00007"},{"key":"S0033291707000700_ref031","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf150"},{"key":"S0033291707000700_ref019","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111134598"},{"key":"S0033291707000700_ref030","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.4.652"},{"key":"S0033291707000700_ref025","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199808240-00033"},{"key":"S0033291707000700_ref059","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2003.10.004"},{"key":"S0033291707000700_ref062","volume-title":"The Wechsler Adult Intelligence Scale\u00a0\u2013\u00a0Revised","author":"Wechsler","year":"1981"},{"key":"S0033291707000700_ref046","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1982.0082"},{"key":"S0033291707000700_ref021","doi-asserted-by":"publisher","DOI":"10.1037\/h0093487"},{"key":"S0033291707000700_ref053","doi-asserted-by":"publisher","DOI":"10.1016\/S0730-725X(98)00099-X"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0033291707000700","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T15:22:45Z","timestamp":1556724165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0033291707000700\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,10]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1]]}},"alternative-id":["S0033291707000700"],"URL":"https:\/\/doi.org\/10.1017\/s0033291707000700","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,10]]}}}