title: ARVCF genetic influences on neurocognitive and neuroanatomical intermediate phenotypes in Chinese patients with schizophrenia.
abstract: OBJECTIVE
  There are notable similarities between velocardiofacial syndrome and schizophrenia in terms of neurocognitive deficits and brain structural abnormalities. These similarities 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.
  
  
  METHODS
  Between May 2006 and November 2009, 200 Chinese participants (125 patients with DSM-IV diagnosis of schizophrenia and 75 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 haplotype T-G-A-T-T-G-G-C-T-G-T (ARVCF-Hap1) was significantly associated with fractional anisotropy of the caudate nucleus and executive functioning in patients. Specifically, patients with more copies of ARVCF-Hap1 have lower white matter integrity in caudate nucleus (P = .0008) and greater perseverative errors (P = .00003) on the Wisconsin Card Sorting Test. A trend of lower caudate volume (P = .015) in patients with more copies of ARVCF-Hap1 was also observed.
  
  
  CONCLUSIONS
  These findings are consistent with known ARVCF gene effects on neurodevelopment in terms of cellular arrangement, migration, and intracellular signaling involving the striatum and may involve interactions with other brain networks such as prefrontal cortex, and they underscore the importance of imaging-genetic studies to elucidate the genetic influences underlying intermediate phenotypes in complex neurobehavioral disorders.
authors: Department of General Psychiatry, Woodbridge Hospital/Institute of Mental Health, Singapore. kang_sim@imh.com.sg
authors: Kang
authors: K
authors: Sim
authors: Wai-Yen
authors: WY
authors: Chan
authors: Puay-San
authors: PS
authors: Woon
authors: Hui-Qi
authors: HQ
authors: Low
authors: Linda
authors: L
authors: Lim
authors: Guo-Liang
authors: GL
authors: Yang
authors: Jimmy
authors: J
authors: Lee
authors: Siow Ann
authors: SA
authors: Chong
authors: Yih-Yian
authors: YY
authors: Sitoh
authors: Yiong Huak
authors: YH
authors: Chan
authors: Jianjun
authors: J
authors: Liu
authors: Ene Choo
authors: EC
authors: Tan
authors: Hywel
authors: H
authors: Williams
authors: Wieslaw Lucjan
authors: WL
authors: Nowinski
mesh_terms: D000328:Adult; D016880:Anisotropy; D051186:Armadillo Domain Proteins / Q000235:genetics*; D044466:Asian People / Q000235:genetics* / Q000523:psychology; D001284:Atrophy / Q000473:pathology; D002421:Caudate Nucleus / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D056324:Diffusion Tensor Imaging / Q000379:methods / Q000523:psychology; D056344:Executive Function; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D012565:Schizophrenic Psychology
chemical_list: C411307:ARVCF protein, human; D051186:Armadillo Domain Proteins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins