Adolescence is a vulnerable time for developing drug addiction, and adolescents who suffer from adolescent bipolar disorder (ABD) are particularly at risk due to the explosive interaction between severe affective dysregulation, impaired self-control, and excessive reward-seeking behavior. In particular, marijuana (cannabis) is the most common illicit substance abused by teenage BD patients. Significant cannabis use in ABD can substantially worsen clinical outcome, with dramatic increases in illness severity, cognitive and affective worsening, and suicide attempts. The nature of the high comorbidity between cannabis use and ABD in the adolescent years, when the brain is still developing, has scarcely been investigated. For the first time, with this pilot study we aim to characterize the mechanistic neuro-circuitry dysfunction associated with high comorbidity between adolescent mental illness such as ABD and SCU (significant cannabis use). Using clinical, neurocognitive, and advanced fMRI methods we will test a model of two brain circuits highly implicated in both drug abuse and bipolar disorder: the reward system and the self-control system. We will test 22 adolescents with significant cannabis use (SCU group), 22 adolescents with ABD and SCU (ABD+SCU group), and 22 healthy controls (HC) using tasks measuring reward sensitivity, and self-control during decision-making involving rewards. All participants with be 14-16 year olds and will be matched on IQ and demographic measures. Our overarching hypothesis is that the fronto-limbic abnormalities typical of bipolar disorder will exacerbate dysfunction in the reward and self-control systems in the ABD+SCU group. This group will exhibit greater reward sensitivity and poorer self-control, associated with hyperactive ventral striatum and amygdala and diminished prefrontal control, relative to the SCU group. Findings from this much needed study will provide a first step towards important neurobiological cues on excessive craving, reward sensitivity and deficient self- control in these patients so difficult to treat. By studying a more homogeneous subgroup with SCU+ABD we may provide insights into drug abuse that were previously unclear due to more heterogeneous collections of SCU. Hence, our findings may extend also to other psychiatric disorders, and give new insights into methods for early detection of SCU.
The dramatically high comorbidity between cannabis use and adolescent bipolar disorder (ABD) is associated with dramatic increases in illness severity, relapses, cognitive and affective decline, and suicide attempts. This study will characterize the mechanistic dysfunction of the brain circuitries underlying comorbid ABD and significant cannabis use (SCU), providing important neurobiological clues on excessive drug-reward sensitivity and poor self-control in these patients so difficult to treat.
|Passarotti, A M; Crane, Natania A; Hedeker, Donald et al. (2015) Longitudinal trajectories of marijuana use from adolescence to young adulthood. Addict Behav 45:301-8|