Brittany E. Evans

Diminished error-related brain activity as a promising endophenotype for substance-use disorders: evidence from high-risk offspring

One of the core features of individuals with a substance‐use disorder (SUD) is the reduced ability to successfully process errors and monitor performance, as reflected by diminished error‐related negativities (ERN). However, whether these error‐related brain abnormalities are caused by chronic substance use or rather predates it remains unclear. The present study elucidated whether hypoactive performance monitoring represents an endophenotypic vulnerability marker for SUD by using a high‐risk paradigm. We assessed the behavioral components of error‐processing, as well as the amplitude of the ERN in the event‐related brain potential (ERP) during performance of the Eriksen Flanker Task among high‐risk adolescents of parents with a SUD (HR; nu2009=u200928) and normal‐risk controls (NR; nu2009=u200940). Results revealed that HR offspring were characterized by a higher prevalence of internalizing symptoms and more frequent cannabis use, the latter having a significant influence on the ERN. Interestingly, risk group uniquely predicted the negativity amplitude in response to error trials above and beyond confounding variables. Moreover, we found evidence of smaller ERN amplitudes in (cannabis use‐naïve) HR offspring, reflecting impaired early processing of error information and suboptimal performance monitoring, whereas no robust group differences were found for overall behavioral performance. This effect was independent of an overall reduction in brain activity. Taken together, although we cannot rule out alternative explanations, the results of our study may provide evidence for the idea that diminished error‐processing represents a promising endophenotype for SUD that may indicate a vulnerability to the disorder.

The effects of psychiatric distress, inhibition, and impulsivity on decision making in patients with substance use disorders: A matched control study

In the present study, the decision making abilities of patients with substance use disorders were compared to those of healthy controls and, subsequently, the impact of psychiatric distress, behavioral inhibition, and impulsivity on Iowa Gambling Task (IGT) performance were evaluated. A total of 31 patients and 31 matched healthy controls performed the IGT and completed the Symptom Checklist-90-Revised (SCL-90-R) and the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS). The results confirmed that the patient group had severe impairments on the IGT relative to the controls, which appeared to be virtually unrelated to the employed measures. It is concluded that self-reported psychiatric symptoms, behavioral inhibition, and impulsivity have no impact on the IGT performance in this patient sample.

Parental rearing behavior prospectively predicts adolescents’ risky decision‐making and feedback‐related electrical brain activity

The present study examined the role of parental rearing behavior in adolescents risky decision-making and the brains feedback processing mechanisms. Healthy adolescent participants (nxa0=xa0110) completed the EMBU-C, a self-report questionnaire onxa0perceived parental rearing behaviors between 2006 and 2008 (T1). Subsequently, after an average of 3.5xa0years, we assessed (a) risky decision-making during performance of the Balloon Analogue Risk Task (BART); (b) event-related brain potentials (ERPs) elicited by positive (gain) and negative feedback (loss) during the BART; and (c) self-reported substance use behavior (T2). Age-corrected regression analyses showed that parental rejection at T1 accounted for a unique and significant proportion of the variance in risk-taking during the BART; the more adolescents perceived their parents as rejecting, the more risky decisions were made. Higher levels of perceived emotional warmth predicted increased P300 amplitudes in response to positive feedback at T2. Moreover, these larger P300 amplitudes (gain) significantly predicted risky decision-making during the BART. Parental rearing behaviors during childhood thus seem to be significant predictors of both behavioral and electrophysiological indices of risky decision-making in adolescence several years later. This is in keeping with the notion that environmental factors such as parental rearing are important in explaining adolescents risk-taking propensities.

Blunted feedback processing during risky decision making in adolescents with a parental history of substance use disorders.

Risky decision making, a hallmark phenotype of substance use disorders (SUD), is thought to be associated with deficient feedback processing. Whether these aberrations are present prior to SUD onset or reflect merely a consequence of chronic substance use on the brain remains unclear. The present study investigated whether blunted feedback processing during risky decision making reflects a biological predisposition to SUD. We assessed event-related potentials elicited by positive and negative feedback during performance of a modified version of the Balloon Analogue Risk Task (BART) among high-risk adolescents with a parental history of SUD (HR; n = 61) and normal-risk controls (NR; n = 91). HR males made significantly more risky and faster decisions during the BART than did NR controls. Moreover, HR adolescents showed significantly reduced P300 amplitudes in response to both positive and negative feedback as compared to NR controls. These differences were not secondary to prolonged substance use exposure. Results are discussed in terms of feedback-specific processes. Reduced P300 amplitudes in the BART may reflect poor processing of feedback at the level of overall salience, which may keep people from effectively predicting the probability of future gains and losses. Though conclusions are tentative, blunted feedback processing during risky decision making may represent a promising endophenotypic vulnerability marker for SUD.

Youth in the Netherlands Study (JOiN): study design

BackgroundAdolescence is a critical developmental period regarding exposure to substances. Therefore, it is important to be able to identify those adolescents who are most vulnerable to substance abuse in the (near) future. The JOiN study was specifically designed to examine two endophenotypes of adolescent substance use in a normal risk (NR) and high risk (HR) sample of adolescents: (1) behavioural disinhibition, and (2) individual differences in stress sensitivity.MethodsThe NR adolescents were part of a longitudinal general population study at the Erasmus Medical Center in Rotterdam, the Netherlands of children and adolescents initially aged 6 to 18 years old. Three assessment waves have been nearly completed, and data are available of N = 711 participants for stress sensitivity measures, and of a subsample of N = 110 for electroencephalography (EEG) measures. Added to this study, HR adolescents who had at least one parent with a substance use disorder and who were treated by an outpatient clinic of a primary addiction care provider were approached via their parent(s). In total, N = 83 adolescents formed this HR sample. NR and HR adolescents participated in standardized stress procedure and EEG procedures in our laboratory. Questionnaires were filled out on background variables, behavioural and emotional problems, and substance use, and a diagnostic interview was conducted with adolescents and parents to assess psychopathology symptoms. DNA was collected through saliva or blood samples.DiscussionThe design of the JOiN study is optimal for examining the predictive role of endophenotypes of adolescent substance use. The combination of different methods, i.e. stress physiology, electrophysiology, genetics, and questionnaire data from several informants on a range of behaviours and environmental factors enables the investigation of the multifactorial nature of adolescent substance use.

Multifactorial determinants of target and novelty-evoked P300 amplitudes in children of addicted parents

Background Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD]) uniquely contributed to P300 amplitude variation above and beyond these other variables. Methods Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80) and normal-risk controls (NR;n=100) while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. Results HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. Conclusion Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents.