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Brain Anatomy in Adults With Velocardiofacial Syndrome With and Without Schizophrenia
Preliminary Results of a Structural Magnetic Resonance Imaging Study
Therese van Amelsvoort, MD, PhD, MRCPsych;
Eileen Daly, BSc;
Jayne Henry, DPsych;
Dene Robertson, MD, MRCPsych, MRCGP;
Virginia Ng, MD, MRCP;
Michael Owen, MD, PhD, FRCPsych;
Kieran C. Murphy, MD, PhD, MRCPsych;
Declan G. M. Murphy, MD, MRCPsych
Arch Gen Psychiatry. 2004;61:1085-1096.
Context Velocardiofacial syndrome is associated with interstitial deletions of chromosome 22q11, mild to borderline learning disability, characteristic dysmorphology, and a high prevalence of schizophrenia. The biological basis for this increased risk for schizophrenia is unknown, but people with velocardiofacial syndrome may have genetically determined differences in brain anatomy that predispose to the development of schizophrenia.
Objective To determine whether there are differences in brain structure between subjects with velocardiofacial syndrome with and without schizophrenia.
Design A cross-sectional quantitative structural magnetic resonance imaging study in 39 adult subjects.
Setting Referrals were made through medical genetics clinics and psychiatric services throughout the United Kingdom.
Participants Thirteen subjects with velocardiofacial syndrome and schizophrenia, 12 with velocardiofacial syndrome without history of a psychosis, and 14 healthy controls volunteered to participate after screening for eligibility.
Main Outcome Measures Total and regional brain volumes were analyzed by means of manual tracing, and gray- and white-matter densities were obtained by computerized voxel-based methods.
Results People with velocardiofacial syndrome and schizophrenia, compared with both controls and nonschizophrenic patients with velocardiofacial syndrome, had a significant (P<.05) reduction in volume of whole-brain (white + gray) matter and whole-brain white matter, and an increase in total and sulcal cerebrospinal fluid volume. Both velocardiofacial syndrome groups had a reduced cerebellar volume compared with controls.
Conclusions Within velocardiofacial syndrome, schizophrenia is associated with generalized differences in brain anatomy, but white matter may be particularly implicated. Studies with larger samples are needed to replicate our findings.
Author Affiliations: Department of Psychological Medicine, Institute of Psychiatry, London, England (Drs van Amelsvoort, Henry, Robertson, K. C. Murphy, and D. G. M. Murphy and Ms Daly); Neuroimaging Department, Maudsley Hospital, London (Dr Ng); Department of Psychiatry, University of Wales College of Medicine, Cardiff (Dr Owen); Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands (Dr van Amelsvoort); and Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin (Dr K. C. Murphy).
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