Endophenotypes of executive functions in obsessive compulsive disorder? A meta-analysis in unaffected relatives Endophenotypes are mediator traits between genetic influences and clinical phenotypes. Meta-analyses have consistently shown modest impairments of executive functioning in obsessive compulsive disorder (OCD) patients compared to healthy controls. Similar deficits have also been reported in unaffected relatives of OCD patients, but have not been quantified. We conducted the first meta-analysis combining all studies investigating executive functioning in unaffected relatives of individuals with OCD to quantify any deficits. A search of Pubmed, Medline and PsychInfo databases identified 21 suitable papers comprising 707 unaffected relatives of OCD patients and 842 healthy controls. Effect sizes were calculated using random effects models. Unaffected relatives displayed a significant impairment in global executive functioning. Analyses of specific executive functioning subdomains revealed impairments in: planning, visuospatial working memory and verbal fluency. Deficits in executive functioning are promising endophenotypes for OCD. To identify further biomarkers of disease risk/resilience in OCD, we suggest examining specific executive functioning domains.

Clinical association to FKBP5 rs1360780 in patients with depression The FKBP5 protein is of importance for the function of the glucocorticoid receptor. The purpose of the present study was to examine the possible association between the different genotypes of rs1360780 in the FKBP5 gene, and clinical symptoms in patients with unipolar depression. Seven hundred eighteen patients and 673 controls from the Danish Psychiatric Biobank were participated. No association was found between any genotype and diagnosis of unipolar depression. It was found that the group of depressed patients with the CC genotype showed significantly earlier start of treatment with medicine, had a significantly greater tendency to be treated with electroconvulsive therapy and showed a significantly higher frequency of family history of depression compared with the combined group of patients with the CT and TT genotypes. The only informations about controls were their sex and that they were recruited from the blood bank. The clinical data were not complete for all patients

Association study of the PDE4D gene and obsessive-compulsive disorder in a Chinese Han population Objective Multiple evidence suggests an involvement of the PDE4D in mental disorders. Therefore we investigate the association between obsessive-compulsive disorder and a polymorphism of the single nucleotide polymorphisms of PDE4D gene in the Chinese Han population. Methods We genotyped and performed a case-control association analysis of the PDE4D polymorphism rs1838733 in 400 obsessive-compulsive disorder patients and 459 healthy control subjects. Results The site conformed to Hardy–Weinberg (P > 0.05), three genotypes (AA, AG, GG) of PDE4D gene rs1838733 were detected. We demonstrated three principal results. First, there were no significant differences between the case and health controls in the genotype and allele at rs1838733 (P > 0.05). Second, there were no significant differences in the allele and genotype frequency between different genders obsessive-compulsive disorder (P > 0.05). Third, the genotype of single nucleotide polymorphism rs1838733 was associated with late-onset obsessive-compulsive disorder and female late-onset obsessive-compulsive disorder (P < 0.05). Conclusion The present study is the first to verify the associations of single nucleotide polymorphisms rs1838733 of the PDE4D gene with obsessive-compulsive disorder in a Chinese Han population. We found the genotype of single nucleotide polymorphism rs1838733 was associated with the occurrence of late-onset obsessive-compulsive disorder and female late-onset obsessive-compulsive disorder. Therefore, PDE4D may play a role in the pathogenesis of obsessive-compulsive disorder and may become a potential target for obsessive-compulsive disorder treatment in future research. Further studies should verify the current findings.

Association between RELN polymorphisms and schizophrenia in a Han population from Northeast China Objective To explore the association between the RELN gene and schizophrenia in the overall sample and samples stratified by sex in a northeastern Chinese population. Methods A total of 1536 participants from Jilin Province, China, were recruited in this case-control study. Four single nucleotide polymorphisms (rs1062831, rs3808039, rs362746, and rs736707) in the RELN gene were genotyped. Binary logistic regression analysis was applied to detect associations between the genotypes of each single nucleotide polymorphism and schizophrenia. P values of no more than 0.003125 [0.05/(4 SNPs*4 different genetic models)] after Bonferroni correction were considered statistically significant. Results All single-nucleotide polymorphisms conformed to Hardy–Weinberg equilibrium in the control group. Logistic regression analysis revealed that after Bonferroni correction, rs362746 was associated with schizophrenia under the recessive model (P = 0.001) and codominant model (P = 0.003) in the overall group. The association between schizophrenia and RELN single-nucleotide polymorphisms was not found in a sex-specific pattern after Bonferroni correction. Conclusion Our study provides and supports the evidence that RELN is a candidate gene for schizophrenia. Replication studies conducted in different populations are required, and the sex-specific association of this gene with schizophrenia warrants further exploration.

Corpus callosum metrics predict severity of visuospatial and neuromotor dysfunctions in ARID1B mutations with Coffin–Siris syndrome ARID1B mutations in Coffin–Siris syndrome are a cause of intellectual disability (0.5–1%), with various degrees of autism and agenesis of the corpus callosum (10%). Little is known regarding the cognitive and motor consequences of ARID1B mutations in humans and no link has been made between corpus callosum anomalies and visuospatial and neuromotor dysfunctions. We have investigated the visuospatial and neuromotor phenotype in eight patients with ARID1B mutations. A paramedian sagittal section of the brain MRI was selected, and corpus callosum was measured in anteroposterior length, genu and trunk width. Spearman’s rank order coefficients were used to explore correlations between visuospatial and social cognitive variables and dimensions of the corpus callosum. A significant correlation between genu width size and visual cognition was observed. Retrocerebellar cysts were associated with corpus callosum anomalies. Here, we show that corpus callosum anomalies caused in ARID1B mutations may be predictive of the visuospatial and motor phenotype in Coffin–Siris syndrome.

A case of intellectual disability reveals a novel mutation in IQSEC2 gene by whole exome sequencing Intellectual disability refers to significantly subaverage intellectual function (intelligence quotient < 70) with impairment of adaptive function. The IQSEC2 gene is one of the pathogenic genes located on chromosome Xp11.22. IQSEC2 is an X-linked gene correlated with intellectual disability and epilepsy. In this study, we reported a 2-year-old male patient presented with reacting sluggishly with people and surroungdings. Active electroencephalogram showed the background of epileptic activity. Brain MRI revealed patchy hyperintensity of bilateral parietal lobe white matter on fluid-attenuated inversion recovery image and widened ventricle, cistern and sulci on T2-weighted image. Delayed myelination was considered. The diagnosis of intellectual disability and epilepsy was made. Whole exome-sequencing was conducted and identified a novel frameshift mutation in exon 15 of IQSEC2 (NM_001111125.2: c.4164dupC: p.Ile1389 Hisfs*218). The variant resulted in the deletion of termination codon, and the protein was extended to termination after stretch of 218 amino acids.This study expands the mutation spectrum of IQSEC2. It supports the published data suggesting that IQSEC2 plays a significant part in patients with intellectual disability and epilepsy. IQSEC2 should be detected in patients with intellectual disability and epilepsy.