Substance Use Disorders in Adolescent and Young Adult Relatives of Probands with Bipolar Disorder: What Drives the Increased Risk?

Background Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. Methods We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006–2011. Youth offspring/relatives (“Relatives of BD probands;” n = 267; mean age = 16.8 years; ± 2.9 S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands (“relatives of control probands;” n = 149; mean age = 17.4 years; ± 2.9 S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. Results Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p = 0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR = 2.80–3.17; p < 0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. Conclusion Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population

Variants Located Upstream of CHRNB4 on Chromosome 15q25.1 Are Associated with Age at Onset of Daily Smoking and Habitual Smoking

Several genome-wide association and candidate gene studies have linked chromosome 15q24–q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking theCHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults