Correlates of comorbid anxiety and externalizing disorders in childhood obsessive compulsive disorder

The present study examines the influence of diagnostic comorbidity on the demographic, psychiatric, and functional status of youth with a primary diagnosis of obsessive compulsive disorder (OCD). Two hundred and fifteen children (ages 5–17) referred to a university-based OCD specialty clinic were compared based on DSM-IV diagnostic profile: OCD without comorbid anxiety or externalizing disorder, OCD plus anxiety disorder, and OCD plus externalizing disorder. No age or gender differences were found across groups. Higher OCD severity was found for the OCD + ANX group, while the OCD + EXT group reported greater functional impairment than the other two groups. Lower family cohesion was reported by the OCD + EXT group compared to the OCD group and the OCD + ANX group reported higher family conflict compared to the OCD + EXT group. The OCD + ANX group had significantly lower rates of tic disorders while rates of depressive disorders did not differ among the three groups. The presence of comorbid anxiety and externalizing psychopathology are associated with greater symptom severity and functional and family impairment and underscores the importance of a better understanding of the relationship of OCD characteristics and associated disorders. Results and clinical implications are further discussed

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established(1). Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity(3-6). Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia(7-8), and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57: P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 54 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023)

Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10−8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p’s < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery

Genetics of early-onset obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is characterized by recurrent, intrusive and disturbing thoughts as well as by repetitive stereotypic behaviors. Epidemiological data are similar in children and adults, i.e., between 1 and 3% of the general population suffer from OCD. Children with OCD are often seriously impaired in their development. OCD, especially of early onset, has been shown to be familial. Several candidate genes of predominantly neurotransmitter systems have been analyzed and a total of three genome-wide linkage scans have been performed until now. Analyses of candidate genes in linkage regions have not provided evidence for their involvement in OCD, with the exception of the glutamate transporter gene SLC1A1 on 9p24. Genome-wide association analyses are in progress and the results will promote further independent replication studies. The consideration of subtypes regarding age of onset, symptom dimensions and/or comorbid disorders is needed