This RO1 resubmission is an application in response to PA-04-100 encouraging research on the origins and pathways to substance abuse (SA). The adult literature indicates that SA is strongly associated with bipolar disorder (BPD). An emerging body of evidence suggests that juvenile BPD may place adolescents at high risk for SA and that adolescents with SA may be at higher risk to have BPD. We have completed baseline assessments in a NIDA funded family study investigating the relationship of SA in juvenile BPD. Using structured psychiatric interviews, objective and subjective measures of SA, a neuropsychological battery, and measures of psychosocial functioning, we have completed comprehensive evaluations on 110 adolescents with bipolar disorder, their siblings and parents;and a control group of 110 non-mood disordered adolescents, their siblings and parents. We now propose a four-year follow-up of this cohort as they pass through the age of risk for SA. Our baseline data is very encouraging in disentangling the risk of SA in BPD. Data analyses from 76% of the families collected reveals that adolescents (mean age 13.5 yrs) with BPD are at higher risk for SA than adolescents without BPD (30% vs 4%, p<0.001) that is not accounted for by conduct disorder. Adolescent-onset BPD (age >12), relative to child-onset BPD, is a greater risk for SA. BPD youth have significantly greater psychiatric comorbidity, neuropsychological impairment, and psychosocial distress, all independent risk factors for later SA. We propose a four-year follow-up of our sample of control and BPD families to evaluate the risk for cigarette, SA, stressors, and associated dysfunction. We will test hypotheses corresponding to four main aims: 1) Evaluating BPD as a risk factor for SA, 2) Characterizing the course and outcome of SA in BPD youth, 3) Evaluating predictors, mediators, and moderators of SA in BPD adolescents and young adults, and 4) Evaluating the course and outcome of high risk siblings of BPD probands. The proposed work is a critical step for several reasons. This is the first, prospective, family-based study of SA in juvenile BPD;no studies have disentangled risk factors in juvenile BPD leading to SA. Since BPD is identifiable and treatable, findings from the four-year follow-up will provide valuable information to formulate prevention and early intervention strategies.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Weinberg, Naimah Z
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Massachusetts General Hospital
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Wilens, Timothy E; Yule, Amy; Martelon, MaryKate et al. (2014) Parental history of substance use disorders (SUD) and SUD in offspring: a controlled family study of bipolar disorder. Am J Addict 23:440-6
Wilens, Timothy E; Martelon, MaryKate; Anderson, Jesse P et al. (2013) Difficulties in emotional regulation and substance use disorders: a controlled family study of bipolar adolescents. Drug Alcohol Depend 132:114-21
Martelon, Marykate; Wilens, Timothy E; Anderson, Jesse P et al. (2012) Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder? Bipolar Disord 14:507-14
Biederman, Joseph; Petty, Carter R; Wozniak, Janet et al. (2011) Impact of executive function deficits in youth with bipolar I disorder: a controlled study. Psychiatry Res 186:58-64
Hua, Liwei L; Wilens, Timothy E; Martelon, MaryKate et al. (2011) Psychosocial functioning, familiality, and psychiatric comorbidity in bipolar youth with and without psychotic features. J Clin Psychiatry 72:397-405
Lorberg, Boris; Wilens, Timothy E; Martelon, Marykate et al. (2010) Reasons for substance use among adolescents with bipolar disorder. Am J Addict 19:474-80
Doyle, A E; Wozniak, J; Wilens, T E et al. (2009) Neurocognitive impairment in unaffected siblings of youth with bipolar disorder. Psychol Med 39:1253-63
Mick, Eric; Wozniak, Janet; Wilens, Timothy E et al. (2009) Family-based association study of the BDNF, COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children. BMC Psychiatry 9:2
Biederman, Joseph; Petty, Carter R; Wilens, Timothy E et al. (2009) Examination of concordance between maternal and youth reports in the diagnosis of pediatric bipolar disorder. Bipolar Disord 11:298-306
Steinbuchel, Petra H; Wilens, Timothy E; Adamson, Joel J et al. (2009) Posttraumatic stress disorder and substance use disorder in adolescent bipolar disorder. Bipolar Disord 11:198-204

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