We conducted a combined genome-wide association (GWAS) analysis of 7,481 individuals affected with bipolar disorder and 9,250 control individuals within the Psychiatric Genomewide Association Study Consortium Bipolar Disorder group (PGC-BD). We performed a replication study in which we tested 34 independent SNPs in 4,493 independent bipolar disorder cases and 42,542 independent controls and found strong evidence for replication. In the replication sample, 18 of 34 SNPs had P value < 0.05, and 31 of 34 SNPs had signals with the same direction of effect (P = 3.8 × 10−7). In the combined analysis of all 63,766 subjects (11,974 cases and 51,792 controls), genome-wide significant evidence for association was confirmed for CACNA1C and found for a novel gene ODZ4. In a combined analysis of non-overlapping schizophrenia and bipolar GWAS samples we observed strong evidence for association with SNPs in CACNA1C and in the region of NEK4/ITIH1,3,4. Pathway analysis identified a pathway comprised of subunits of calcium channels enriched in the bipolar disorder association intervals. The strength of the replication data implies that increasing samples sizes in bipolar disorder will confirm many additional loci.

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The observed familiality should be accounted for in criminological research, applied violence risk assessment, and prevention efforts.

Background There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse. Methods Using Swedish national registers, we studied all individuals born 1960–1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits. Results ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57–0.84). Also the longer duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse. Conclusions We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients.

Context Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy causes increased risk of offspring substance use/problems. Objective To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design. Design We used two separate samples, from the United States and from Sweden, respectively. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding. Setting Sample 1: Offspring of a representative sample of women in the United States. Sample 2: The total Swedish population born over 13 years. Patients or Other Participants Sample 1: Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n=6,094). Sample 2: All offspring born in Sweden from 1983 through 1995 (n=1,187,360). Main Outcome Measures Sample 1: Self-reported adolescent alcohol, cigarette, and marijuana use, and early onset (before age 14 years) of each substance. Sample 2: Substance-related convictions and hospitalizations for an alcohol- or drug-related problem. Results The same pattern emerged for each index of substance use/problems across the two samples. At the population level maternal smoking during pregnancy predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (HRmoderate=1.32, CI=1.22–1.43; HRhigh=1.33, CI=1.17=1.53) to a narcotic convictions (HRmoderate=2.23, CI=2.14–2.31; HRhigh=2.97, CI=2.86–3.09). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant. Conclusions The association between maternal smoking during pregnancy and offspring substance use/problems was likely due to familial background factors, not a causal influence, because siblings had similar rates of substance use and problems regardless of their specific exposure to smoking during pregnancy.