Waszczuk and colleagues investigated the phenotypic associations between depression and anxiety disorder symptom subscales and tested the genetic structures underlying these symptoms (DSM-5–related, unidimensional and bidimensional) across 3 developmental stages: childhood, adolescence, and early adulthood.
Individual differences in cannabis sensitivity may be associated with genetic risk for psychotic disorder.
To demonstrate and replicate, using 2 conceptually different genetic epidemiological designs, that (familial) liability to psychosis is associated with sensitivity to cannabis.
Sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder (n = 1120), their siblings (n = 1057), and community controls (n = 590) in the Netherlands and Flanders.
Positive and negative schizotypy using the Structured Interview for Schizotypy–Revised (for siblings and controls) and self-reported positive and negative psychotic experiences using the Community Assessment of Psychic Experiences (for siblings and patients). Cannabis use was assessed as current use (by urinalysis) and lifetime frequency of use (by Composite International Diagnostic Interview).
In the sibling-control comparison, siblings displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis (adjusted B = 0.197, P < .001) than controls (adjusted B = 0.013, P = .86) (P interaction = .04) and a similar difference in sensitivity to its effect on negative schizotypy (siblings: adjusted B = 0.120, P < .001; controls: B = −0.008, P = .87; P interaction = .03). Similarly, siblings exposed to cannabis resembled their patient relative nearly 10 times more closely in the positive psychotic dimension of the Community Assessment of Psychic Experiences (adjusted B = 0.278, P < .001) compared with nonexposed siblings (adjusted B = 0.025, P = .12) (P interaction < .001). No significant effect was apparent for the Community Assessment of Psychic Experiences negative domain, although the association was directionally similar (2 times more resemblance; P interaction = .17). Cross-sibling, cross-trait analyses suggested that the mechanism underlying these findings was moderation (familial risk increasing sensitivity to cannabis) rather than mediation (familial risk increasing use of cannabis).
Genetic risk for psychotic disorder may be expressed in part as sensitivity to the psychotomimetic effect of cannabis. Cannabis use may synergistically combine with preexisting psychosis liability to cause positive and negative symptoms of psychosis.
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.
This cross-sectional study demonstrates that psychiatric comorbidities are common among individuals with Tourette syndrome and that most comorbidities begin early in life.
This twin study uses structural equation modeling to examine whether white matter integrity is associated with the genetic liability for developing schizophrenia.
Monzani et al estimate the degree to which genetic and environmental risk factors are shared and/or unique to dimensionally scored obsessive compulsive disorder, body dysmorphic disorder, hoarding disorder, trichotillomania (hair-pulling disorder), and excoriation (skin-picking) disorder.
Reichborn-Kjennerud et al determine the structure of genetic and environmental risk factors for the symptoms of borderline personality disorder.
This cross-sectional study using a sample of twins/siblings reports that differences in amygdala volume in cannabis users are attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences of cannabis use.
Blasi et al examine the functional effects of the serotonin receptor 2a (5-HT2AR) gene on 5-HT2AR
messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for
schizophrenia, and on treatment with olanzapine.