Elevated Risk For Substance Use Disorders Research Articles

Reward Processing in Drug-Naive Youth with Various Levels of Risk for Substance Use Disorders: A Pilot Study.

Background: It has been hypothesized that attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) share common neurobiological features. When abnormalities in the mesolimbic reward system are characteristic of children with ADHD, it is unclear whether youth at particularly elevated risk for SUD may exhibit any further disturbances. The objective of this pilot study is to examine possible neurobiological differences among youth with different levels of SUD risk before exposure to any abusable substances. Methods: We recruited 47 drug-naive children aged 8-13 divided into (1) Low Risk (LR)-ADHD only (n = 16); (2) High Risk (HR)-ADHD+familial SUD (n = 17); and (3) healthy controls (HC, n = 14) who underwent one functional magnetic resonance imaging scan while performing a hybrid task. We used the omnibus analysis of covariance model to assess for group differences in brain activation in regions linked to the brain reward and behavioral control systems. Results: Behavioral analysis showed significant Cue and Flanker main effects, but no significant main effect for Group. Whole-brain analysis showed significant differences in widely distributed networks related to both reward processing and behavioral control. Region of interest (ROI) activations showed that the HR group had the highest activation in the right putamen during both expected rewards and unexpected nonreward outcomes and in the anterior cingulate cortex (ACC) during unexpected nonreward outcomes, while LR and HC youth showed similarly low activation during these contrasts. Furthermore, the LR and HR groups showed lower activation than HC in the right ACC and the right caudate during flanker contrasts. Conclusions: These are the first preliminary results to demonstrate that the magnitude of activation during reward notification differs as a function of reward outcome in youth at high versus LR for SUD, such that youth at LR for SUD exhibit the highest activation for positive rewards, whereas those at HR for SUD exhibit the highest activation during negative rewards.

Neural activation during risky decision-making in youth at high risk for substance use disorders

Risky decision-making, particularly in the context of reward-seeking behavior, is strongly associated with the presence of substance use disorders (SUDs). However, there has been little research on the neural substrates underlying reward-related decision-making in drug-naïve youth who are at elevated risk for SUDs. Participants comprised 23 high-risk (HR) youth with a well-established SUD risk phenotype and 27 low-risk healthy comparison (HC) youth, aged 10–14. Participants completed the balloon analog risk task (BART), a task designed to examine risky decision-making, during functional magnetic resonance imaging. The HR group had faster reaction times, but otherwise showed no behavioral differences from the HC group. HR youth experienced greater activation when processing outcome, as the chances of balloon explosion increased, relative to HC youth, in ventromedial prefrontal cortex (vmPFC). As explosion probability increased, group-by-condition interactions in the ventral striatum/anterior cingulate and the anterior insula showed increasing activation in HR youth, specifically on trials when explosions occurred. Thus, atypical activation increased with increasing risk of negative outcome (i.e., balloon explosion) in a cortico-striatal network in the HR group. These findings identify candidate neurobiological markers of addiction risk in youth at high familial and phenotypic risk for SUDs.

Attention-Deficit/Hyperactivity Disorder and Risk for Substance Use Disorders in Relatives

BackgroundPrevious research indicates that attention-deficit/hyperactivity disorder (ADHD) is highly associated with substance use disorders (SUD). However, these studies have failed to clarify the nature of the overlap. The main aim of this study was to explore whether the overlap between ADHD and SUD could be explained by shared genetic and environmental factors or by harmful effects of ADHD medication. MethodsWe employed a matched cohort design across different levels of family relatedness recorded from 1973–2009. By linking longitudinal Swedish national registers, 62,015 ADHD probands and first-degree and second-degree relatives were identified and matched 1:10 with control subjects without ADHD and their corresponding relatives. Any record of SUD was defined by discharge diagnoses of the International Classification of Diseases or a purchase of any drug used in the treatment of SUD. ResultsFirst-degree relatives of ADHD probands were at elevated risk for SUD (odds ratios 2.2 and 1.8) compared with relatives of control subjects. The corresponding relative risk in second-degree relatives was substantially lower (odd ratios 1.4 and 1.4). The familial aggregation patterns remained similar for first-degree and second-degree relatives after excluding individuals with coexisting disorders such as schizophrenia, bipolar disorder, depression, and conduct disorder. ConclusionsOur findings suggest that the co-occurrence of ADHD and SUD is due to genetic factors shared between the two disorders, rather than to a general propensity for psychiatric disorders or harmful effects of ADHD medication.

Gender Differences in the Association Between Family Conflict and Adolescent Substance Use Disorders

The objectives of this study were (1) to examine whether the association between childhood family conflict and the risk of substance use disorders (SUDs) in adolescence differs by gender, and (2) to determine whether anxious/depressive symptoms and conduct problems explain this association among adolescent males and females. Data were obtained from 1,421 children aged 10-16 years at the time of enrollment in the Project on Human Development in Chicago Neighborhoods. We assessed gender differences in the association between childhood family conflict and adolescent SUDs by fitting a logistic regression model that included the interaction of gender and family conflict. We also investigated whether conduct problems and anxious/depressive symptoms explained the association between family conflict and SUDs differently for males and females through gender-specific mediation analyses. The association between childhood family conflict and SUDs in adolescence differed by gender (p = .04). Family conflict was significantly associated with SUDs among females (OR: 1.61; CI: 1.20-2.15), but not among males (OR: 1.00; CI: .76-1.32). The elevated risk of SUDs among females exposed to family conflict was partly explained by girls' conduct problems, but not by anxious/depressive symptoms. Females living in families with elevated levels of conflict were more likely to engage in acting out behaviors, which was associated with the development of SUDs. Future epidemiologic research is needed to help determine when this exposure is most problematic with respect to subsequent mental health outcomes and the most crucial time to intervene.

Cognitive Enhancement: Promises and Perils

The potential use of drugs to enhance cognition, emotion, and executive function has engendered controversy despite the fact that few such agents exist today. Here, I provide a context for discussions based on medical, regulatory, and ethical concerns that have been raised by the possibility that enhancers will emerge from current efforts to discover drugs for neuropsychiatric disorders.