This population-based case-control cohort study examines the risk for psychiatric and neurodevelopmental disorders among the full siblings of probands with autism spectrum disorder.
This cohort study using Swedish population registers quantifies the nature and extent of nonrandom mating, within and across a broad range of psychiatric conditions, at the population level.
This international cohort study assesses the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits in carriers and compared these findings with effects in 16p11.2 deletion carriers and the relatives of both groups.
This family-based analysis of de novo copy number variants finds significant parent-proband correlations between family background and phenotypic variability.
This prospective study found that parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder.
Mathew et al characterize medial temporal lobe structures, including hippocampal subfields, using magnetic resonance imaging and examine their relation to psychosis and cognitive function across the psychosis spectrum.
Kendler and coauthors examine how strongly peer deviance increases the risk of drug abuse.
To provide estimates of familial risk for and heritability of obsessive-compulsive disorder
(OCD), Mataix-Cols et al performed population-based, multigenerational, case-control family and twin
studies using Swedish registries. Included were all individuals diagnosed as having OCD between 1969
and 2009 and their available relatives.
Individual differences exist in sensitivity to the psychotomimetic effect of cannabis; the molecular genetic basis underlying differential sensitivity remains elusive.
To investigate whether selected schizophrenia candidate single-nucleotide polymorphisms (SNPs) moderate effects of cannabis use.
Interactions between recent cannabis use, determined by urinalysis results, and 152 SNPs in 42 candidate genes were examined in 740 unaffected siblings of 801 patients with psychosis to examine genetic moderation of the association between Structured Interview for Schizotypy–Revised positive schizotypy and recent cannabis use (at-risk paradigm). The SNPs showing Bonferroni-adjusted association in the at-risk paradigm were used in a case-only analysis in the 801 patients, as well as in a case-sibling and case-control analysis (using 419 controls) focusing on genetic moderation of developmental effects of cannabis on later psychotic disorder.
The Netherlands and Flanders, Belgium.
Eight hundred one patients with psychosis and their 740 unaffected siblings.
Significant interaction between any of the selected SNPs and cannabis in the at-risk paradigm, followed by selective case-only, case-sibling, and case-control analyses.
In the unaffected siblings, 16 SNPs in 12 genes showed significant interaction at P < .05, 3 of which survived correction for multiple testing (P < .0003), situated in AKT1 (rs2494732 and rs1130233) and LRRTM1 (rs673871). Follow-up analysis supported AKT1 rs2494732 × cannabis interaction in the case-only (β = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis. In the unaffected siblings, the AKT1 × cannabis interaction explained 2.2% additional variance in schizotypy in the whole sample and 19.0% additional variance in the exposed siblings with recent cannabis use.
Genetic variation in AKT1 may mediate both short-term as well as longer-term effects on psychosis expression associated with use of cannabis, possibly through a mechanism of cannabinoid-regulated AKT1/GSK-3 signaling downstream of the dopamine D2 receptor.