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Background: The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first- episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation. Methods: We genotyped 2 single nucleotide polymorphisms (SNPs; rs1938526 and rs10994336) in ANK3 in patients with FEP. Multivariate analysis of variance compared risk allele carriers and noncarriers on 6 domains of cognition consistent with MATRICS consensus. A subsample of 82 patients was assessed using magnetic resonance imaging. We compared brain structure between carriers and noncarriers using cortical thickness analysis and voxel-based morphometry on white matter. Results: In the 173 patients with FEP included in our study, rs1938526 and rs10994336 were in very high linkage disequilibrium (d' = 0.95), and analyses were therefore only carried out on the SNP (rs1938526) with the highest minor allele frequency (G). Allele G of rs1938526, was associated with lower cognitive performance across domains ([F.sub.6,164] = 2.38, p = 0.030) and significantly lower scores on the domains of verbal memory (p = 0.015), working memory (p = 0.006) and attention (p = 0.019). The significant effects of this SNP on cognition were not maintained when controlling for IQ. Cortical thinning was observed in risk allele carriers at diverse sites across cortical lobes bilaterally at a threshold of p < 0.01, false discovery rate-corrected. Risk- allele carriers did not show any regions of reduced white matter volume. Limitations: The sample size is modest given that a low-frequency variant was being examined. Conclusion: The ANK3 risk allele rs1938526 appears to be associated with general cognitive impairment and widespread cortical thinning in patients with FEP., Introduction Evidence suggests that psychotic disorders are partly of genetic origin; however, the search for candidate genes has been challenging because these are complex disorders involving the contribution of multiple [...]

Abstract Background Brahma (BRM) is a key component of the multisubunit SWI/SNF complex, a complex which uses the energy of ATP hydrolysis to remodel chromatin. BRM contains an N-terminal polyglutamine domain, encoded by a polymorphic trinucleotide (CAA/CAG) repeat, the only known polymorphism in the coding region of the gene (SMARCA2). We have examined the association of this polymorphism with schizophrenia in a family-based and case/control study. SMARCA2 was chosen as a candidate gene because of its specific role in developmental pathways, its high expression level in the brain and some evidence of its association with schizophrenia spectrum disorder from genome-wide linkage analysis. Results Family-based analysis with 281 complete and incomplete triads showed that there is no significant preferential transmission of any of the alleles to the affected offspring. Also, in the case/control analysis, similar allele and genotype distributions were observed between affected cases (n = 289) and unaffected controls (n = 273) in each of three Caucasian populations studied: French Canadian, Tunisian and other Caucasians of European origin. Conclusion Results from our family-based and case-control association study suggest that there is no association between the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia.

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.Neuropsychopharmacology (2007) 32, 1370–1376. doi:10.1038/sj.npp.1301240; published online 25 October 2006 [ABSTRACT FROM AUTHOR]

The Nogo gene was putatively implicated in schizophrenia based on gene expression and genetic association data. In this study, we attempt to replicate the possible association of the CAA insertion and a nearby TATC deletion with schizophrenia in 204 complete and incomplete triads and in a sample of 462 unrelated cases and 153 controls, all of Caucasian origin. Our genotyping results indicated that neither the trinucleotide insertion polymorphism (CAAins; 43.4% vs. 41.8%, p>0.5) nor the polymorphism-TATC deletion (TATCdel; 49.8% vs. 49.3%, p>0.1) allele frequency is significantly different in patients compared to controls. The homozygous CAAins frequency is not significantly different between patients and controls either (18.0% vs. 15.0%, chi2=0.985, p>0.1). Furthermore, neither CAAins/TATCdel individually, nor the haplotype carrying both CAAins and TATCdel is preferentially transmitted to affected offspring.