Elisa M. Trucco

Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation

IMPORTANCE Marijuana use may alter ventral striatal response to reward, which might heighten susceptibility to substance use disorder. Longitudinal research is needed to determine the effects of marijuana use on neural function involved in reward response. OBJECTIVE To determine whether marijuana use among young adults prospectively affects nucleus accumbens (NAcc) activation during reward anticipation. DESIGN, SETTING, AND PARTICIPANTS One hundred eight young adults were recruited from the Michigan Longitudinal Study, an ongoing study of youth at high risk for substance use disorder and a contrast sample of control families. Participants underwent 3 consecutive functional magnetic resonance imaging scans at approximate ages of 20 (time 1), 22 (time 2), and 24 (time 3) years. Self-report data on marijuana and other drug use occasions were collected annually since age 11 years. MAIN OUTCOMES AND MEASURES Cross-lagged models were used to test the association of marijuana use with neural response in the NAcc to reward anticipation during a monetary incentive delay task controlling for sex, age, other substance use, and family history of substance use disorder. RESULTS Of 108 participants, 39 (36.1%) were female and mean (SD) age at baseline was 20.1 (1.4) years. Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β = -0.26, P = .04; time 2 to time 3: β = -0.25, P = .01). When the cross-lagged model was tested with the inclusion of previous and concurrent cigarette use, the effect of marijuana use from time 2 to time 3 remained significant (β = -0.29; P = .005) and the effect of cigarette use was nonsignificant. CONCLUSIONS AND RELEVANCE The findings of this study indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of nondrug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase the risk for continued drug use and later addiction.

Susceptibility effects of GABA receptor subunit alpha-2 ( GABRA2 ) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele

Understanding factors increasing susceptibility to social contexts and predicting psychopathology can help identify targets for prevention. Persistently high externalizing behavior in adolescence is predictive of psychopathology in adulthood. Parental monitoring predicts low externalizing behavior, yet youth likely vary in the degree to which they are affected by parents. Genetic variants of GABA receptor subunit alpha-2 (GABRA2) may increase susceptibility to parental monitoring, thus impacting externalizing trajectories. We had several objectives: (a) to determine whether GABRA2 (rs279827, rs279826, rs279858) moderates the relationship between a component of parental monitoring, parental knowledge, and externalizing trajectories; (b) to test the form of this interaction to assess whether GABRA2 variants reflect risk (diathesis-stress) or susceptibility (differential susceptibility) factors; and (c) to clarify GABRA2 associations on the development of problem behavior. This prospective study (N = 504) identified three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. A GABRA2 × Parental Monitoring effect on class membership was observed, such that A-carriers were largely unaffected by parental monitoring, whereas class membership for those with the GG genotype was affected by parental monitoring. Findings support differential susceptibility in GABRA2.

Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use

Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high-risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self-reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent nonspecific neurobiological underpinnings for an externalizing pathway to addiction. (PsycINFO Database Record

Genetic variation in GABRA2 moderates peer influence on externalizing behavior in adolescents

Genetic predisposition and environmental influences are both important factors in the development of problematic behavior leading to substance use in adolescence. Involvement with delinquent peers also strongly predicts adolescent externalizing behavior. Several lines of evidence support a role of GABRA2 on externalizing behavior related to disinhibition. However, whether this genetic association is influenced by the environment such as peer behavior remains unknown.

Cognitive Appraisals of Alcohol Use in Early Adolescence: Psychosocial Predictors and Reciprocal Associations with Alcohol Use.

Early adolescence is a dynamic period for the development of alcohol appraisals (expected outcomes of drinking and subjective evaluations of expected outcomes), yet the literature provides a limited understanding of psychosocial factors that shape these appraisals during this period. This study took a comprehensive view of alcohol appraisals and considered positive and negative alcohol outcome expectancies, as well as subjective evaluations of expected outcomes. Developmental-ecological theory guided examination of individual, peer, family, and neighborhood predictors of cognitive appraisals of alcohol and use. A community sample of 378 adolescents ( X ¯ age 11.5 years at Wave 1 (W1), 52% female) was assessed annually for 4 years. Longitudinal path analysis suggested that the most robust predictors of alcohol appraisals were peer norms. Furthermore, perceived likelihood of positive and negative alcohol outcomes prospectively predicted increases in drinking. There was limited support for appraisals operating as mediators of psychosocial risk and protective factors.

A brief validated screen to identify boys and girls at risk for early marijuana use.

To guide recruitment, the ABCD Study requires a method for identifying children at high risk for early-onset substance use that may be utilized during the recruitment process. This study was undertaken to inform the development of a brief screen for identifying youths’ risk of early-onset substance use and other adverse outcomes. To be acceptable by participants in this context, consideration of potential items was limited to child characteristics previously determined to be potentially pertinent and parental cigarette smoking. To focus the analyses on a single target substance use outcome pertinent to the stated goals of the ABCD Study, early-onset marijuana use was selected. Utilizing data collected prior to the initiation of the ABCD Study, four longitudinal data sets were used in nine secondary data analyses to test, replicate and validate a brief screening assessment for boys and girls to identify those at risk for early-onset marijuana use by ages 14–15. The combination of child externalizing problems reported by the parent (4 items: destroys things belonging to his/her family or others; disobedience at school; lying or cheating; steals outside the home) and parent smoking (1 item) proved to be the optimal screen. This was largely replicated across the four data sets. Indicators of predictive efficiency were modest in magnitude and statistically significant in 8 out of the 9 analyses. The results informed the screen’s optimal threshold for identifying children at risk for early-onset marijuana use. The addition of child internalizing problems did not improve these predictions. Further analyses showed the predictive utility of the screen for several other substance use outcomes at ages 15 to 18, including alcohol and nicotine use. The results support the use of a short screening assessment to identify youth at risk for early-onset substance use in the ABCD Study and other research.

Beyond risk: Prospective effects of GABA Receptor Subunit Alpha-2 ( GABRA2 ) × Positive Peer Involvement on adolescent behavior

Research on Gene × Environment interactions typically focuses on maladaptive contexts and outcomes. However, the same genetic factors may also impact susceptibility to positive social contexts, leading to adaptive behavior. This paper examines whether the GABA receptor subunit alpha-2 (GABRA2) single nucleotide polymorphism rs279858 moderates the influence of positive peer affiliation on externalizing behavior and various forms of competence. Regions of significance were calculated to determine whether the form of the interaction supported differential susceptibility (increased sensitivity to both low and high positive peer affiliation) or vantage sensitivity (increased sensitivity to high positive peer affiliation). It was hypothesized that those carrying the homozygous minor allele (GG) would be more susceptible to peer effects. A sample (n = 300) of primarily male (69.7%) and White (93.0%) adolescents from the Michigan Longitudinal Study was assessed from ages 12 to 17. There was evidence for prospective Gene × Environment interactions in three of the four models. At low levels of positive peer involvement, those with the GG genotype were rated as having fewer adaptive outcomes, while at high levels they were rated as having greater adaptive outcomes. This supports differential susceptibility. Conceptualizing GABRA2 variants as purely risk factors may be inaccurate. Genetic differences in susceptibility to adaptive environmental exposures warrants further investigation.

Interpersonal and intrapersonal emotional processes in individuals treated for alcohol use disorder and non-addicted healthy individuals

INTRODUCTION Prior work largely confirms the presence of various emotional processing deficits among individuals with an alcohol use disorder (AUD); however, their specificity and relevance still warrant investigation. The aim of the current study was to compare selected aspects of emotional processing (i.e., mental state recognition, alexithymia, and emotional intelligence) between individuals treated for an AUD and healthy individuals. METHODS The AUD sample consisted of 92 abstinent men with AUD who were participating in an 8-week inpatient abstinence-based treatment program in Warsaw, Poland. The healthy control (HC) group consisted of 86 men recruited from the Medical University of Warsaw and the Nowowiejski Hospital administrative staff. Baseline information about demographics, psychopathological symptoms, and severity of alcohol problems was obtained. Mental states recognition was assessed using the Reading the Mind in the Eyes Test (RMET). Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). The Schutte Self-Report Emotional Intelligence Test (SSEIT) was used to measure emotional intelligence (EI). RESULTS AND CONCLUSIONS After accounting for potentially confounding variables (demographics, severity of depression, anxiety symptoms) in MANCOVA models, patients with AUD presented deficits in identification and description of their own emotional states, as well as lower emotion regulation skills when compared to HCs. No between-group differences were observed in self-reported recognition of other peoples emotions, social skills, and a behavioral measure of mental states recognition. Specific rather than general emotion-processing deficits in participants with AUD were identified, suggesting problems with processing of intrapersonal emotional signals.

Effects of the serotonin transporter gene, sensitivity of response to alcohol, and parental monitoring on risk for problem alcohol use

The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) has been previously associated with alcohol-related risk. Most findings point to short (S) allele carriers being at increased risk for negative alcohol outcomes relative to long allele homozygotes, although some work indicates a more complex relationship. The current prospective study aimed to clarify how and under what circumstances variations in 5-HTTLPR transmit risk for various alcohol-related outcomes. Participants were 218 adolescents and young adults (29% female) enrolled in the Michigan Longitudinal Study. We tested a moderated mediation model with 5-HTTLPR as the predictor, Self-Rating of the Effects of Alcohol (SRE) score as the mediator, alcohol-related outcomes as the dependent variables, parental monitoring as the moderator of the SRE to alcohol outcomes path, and prior drinks, sex, age, and body mass index as covariates. Four alcohol-related outcomes were tested. The S allele was associated with higher SRE scores (i.e., lower response to alcohol). Parental monitoring was a significant moderator: At low levels of parental monitoring, higher SRE scores predicted more drinks consumed and binge drinking episodes. At high levels of monitoring, higher SRE scores were significantly related to fewer alcohol-related problems. Findings suggest that one mechanism by which 5-HTTLPR variation transmits alcohol-related risk is through level of response to alcohol. Furthermore, the strength and direction of this effect varied by level of parental monitoring, indicating that even in the presence of genetic and physiological vulnerability, parents can influence the likelihood of offspring developing problematic alcohol-related behaviors.

The association between impulsivity, emotion regulation, and symptoms of alcohol use disorder

Emotion dysregulation and impulsivity are important factors influencing the development and course of alcohol dependence. However, few empirical studies investigate the association between different aspects of impulsivity (cognitive, attentional, behavioral), emotion regulation, and alcohol use disorder symptoms in the same model. The goal of this study was to assess the association between emotion regulation and different facets of impulsivity among patients with an alcohol use disorder and healthy controls. The sample was comprised of 273 individuals: 180 participants with an alcohol use disorder undergoing inpatient alcohol treatment and 93 healthy controls. Emotion regulation was assessed using the Schutte Self-Report Emotional Intelligence Test subscale. Impulsivity was assessed with Barratts Impulsiveness Scale (BIS-11). Statistical models tested both the BIS-11 total score, as well as three secondary factors (non-planning, attentional, and motor impulsivity). Findings indicate that individuals with alcohol use disorder symptoms were characterized by poor emotion regulation and high levels of impulsivity in all analyzed domains. Moreover, path analytic models indicated that after accounting for demographic factors (i.e., biological sex, age, education) there was evidence for a significant indirect effect of alcohol use disorder symptomatology on non-planning and attentional impulsivity via emotion regulation. There was no association between emotion regulation and motor impulsivity. These findings indicate the importance of targeting emotion regulation skills as well as behavioral control when treating patients with alcohol use disorder.