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ARVCF genetic influences on neurocognitive and neuroanatomical intermediate phenotypes in Chinese patients with schizophrenia

Sim, Kang, Chan, Wai-Yen, Woon, Puay-San, Low, Hui-Qi, Lim, Linda, Yang, Guo-Liang, Lee, Jimmy, Chong, Siow Ann, Sitoh, Yih-Yian, Chan, Yiong Huak, Liu, Jianjun, Tan, Ene Choo, Williams, Hywel John and Nowinski, Wieslaw Lucjan 2012. ARVCF genetic influences on neurocognitive and neuroanatomical intermediate phenotypes in Chinese patients with schizophrenia. Journal of Clinical Psychiatry 73 (3) , pp. 320-326. 10.4088/JCP.10m06491

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Abstract

Objective: There are notable similarities between velocardiofacial syndrome and schizophrenia in terms of neurocognitive deficits and brain structural abnormalities. These similiarities have supported the role of the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) as a susceptibility gene in schizophrenia. This study investigated the relationships between haplotypes of the ARVCF gene and specific intermediate phenotypes in schizophrenia. We hypothesized that ARVCF gene haplotypes influence caudate nucleus volume, fractional anisotropy, and neurocognitive functioning in schizophrenia. Method: Between May 2006 and November 2009, 200 Chinese participants (125 patients with DSM-IV diagnosis of schizophrenia and 67 controls)were genotyped using blood samples, and a subset of 166 participants (99 patients with DSM-IV diagnosis of schizophrenia and 67 controls) underwent structural magnetic resonance imaging, diffusion tensor imaging, and completed neuropsychological testing. Results: The halotype T-G-A-T-T-G-G-C-T-G-T (AVRCF-Hap1) was significantly associated with fractional anisotropy of the caudate nucleus and executive functioning in patients. Specifically, patients with more copies of AVRCF-Hap1 have lower white matter integrity in caudate nucleus (P=.0008) and greater preservative errors (P=.00003) on the Wisconsin Card Sorting Test. A trend of lower caudate volume (P=.015) in patients with more copies of AVRCF-Hap1 was also observed. Conclusion: These findings are consistent with known AVRCF gene effects on neurodevelopment in terms of cellular arrangement, migration, and intercellular signaling involving the striatum and may involve interactions with other brain networks as prefrontal cortex, and they underscore the importance of imaging-genetic studies to elucidate the genetic influences underlying intermediate phenotypes in complex neurobehavioral disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Physicians Postgraduate Press
ISSN: 0160-6689
Last Modified: 17 Jan 2020 08:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/29890

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