Longitudinal Associations of Childhood Internalizing Psychopathology With Substance Misuse: A Register-Based Twin and Sibling Study

The pathways from internalizing psychopathology to substance misuse remain largely unclear. We estimated associations between childhood internalizing problems and subsequent substance misuse in 2 family-based samples. We also investigated sex differences and the role of externalizing comorbidity. We studied associations of childhood internalizing psychopathology with register-based substance misuse after age 13 years. Sample 1 included all individuals born in Sweden from 1984 to 2000 (N = 1,768,516). Depressive and anxiety disorders were included as register-based International Classification of Diseases Ninth Revision (ICD-9) or Tenth Revision (ICD-10) diagnoses before age 13. Sample 2 was a subsample within the population sample, the Child and Adolescent Twin Study in Sweden (CATSS) twin cohort (n = 12,408; born 1992–1998), with mood and anxiety problems assessed at age 9/12 by parents. In both samples, substance misuse was defined as an ICD-9/10 alcohol/drug use disorder or an alcohol/drug-related criminal conviction until December 2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. In the population sample, both depressive (hazard ratio [HR] = 2.75, 95% CI = 2.36–3.20) and anxiety disorders (HR = 1.52, 95% CI = 1.35–1.73) were associated with substance misuse. Childhood mood problems (HR = 2.28, 95% CI = 1.69–3.08) were associated with substance misuse in the CATSS sample. The associations were partially explained by familial factors, and comorbid externalizing disorders explained the associations in men but not in women. Childhood mood problems were associated with substance misuse, but familial factors shared by siblings partially explained the associations. The relationship of anxiety with substance misuse was complex and depended on measurement and the type of anxiety disorder. Internalizing problems may be especially important for substance misuse risk in women.