Examining Within- and Between-Person Facets of Negative Affect and Associations with Daily Craving Among Young Adults in Substance Use Disorder Recovery.

The role of negative affect in precipitating drug craving and relapse among young adults in recovery from substance use disorder (SUD) is well documented. However, most studies focus on negative affect as a trait-level congregate of multiple negative emotion states. The present study examined the associations between specific facets of negative affect, college stressors, and craving among young adult college students in SUD recovery. Data were drawn from a three-week daily diary study of 50 students participating in a collegiate recovery community at a U.S. university (M age = 21.42, 76% males). At the within-person level, craving was higher on days when young adults experienced higher than usual anger, fear, and sadness, but not guilt. At the between-person level, individuals higher in agitation reported greater levels of craving on average. Moderation analyses further showed that college stressors heightened the within-person association between anger and craving. Findings demonstrate that negative affect is not monolithic and that its different aspects are uniquely associated with craving at both between- and within-person levels. Findings from this study could guide collegiate SUD recovery programs that wish to provide greater support to their members by helping them identify both individual- and time-specific relapse risks, such as generally high levels of agitation or days when anger, fear, or sadness are higher than usual for a particular individual. Our findings also suggest that future research should consider distinct features and implications of affective structures at between- and within-person levels, and how these may be uniquely associated with craving.

Longitudinal Links between Adolescent and Peer Conduct Problems and Moderation by a Sensitivity Genetic Index.

The most extensively studied influence on adolescent conduct problem behaviors is peers, and the literature points to genetics as one source of individual differences in peer influence. The purpose of this study was to test the hypothesis that an environmental sensitivity genetic index comprised of DRD4, 5-HTTLPR, and GABRA2 variation would moderate the association between peer and adolescent conduct problems. Latent growth modeling was applied to PROSPER project longitudinal data from adolescents and their peers. Results showed the hypothesis was supported; adolescents with more copies of putative sensitivity alleles were more strongly influenced by their peers. The interaction form was consistent with differential susceptibility in follow-up analyses. Strengths and weaknesses of genetic aggregates for sensitivity research are discussed.

Effectiveness and Utility of Mobile Device Assessment of Subjective Craving during Residential Opioid Dependence Treatment.

Background: Craving is a dynamic state that is both theoretically and empirically linked to relapse in addiction. Static measures cannot adequately capture the dynamic nature of craving, and research has shown that these measures are limited in their capacity to link craving to treatment outcomes. Methods: The current study reports on assessments of craving collected 4x-day across 12 days from 73 patients in residential treatment for opioid dependence. Analyses investigated whether the within-person assessments yielded expected across- and within-day variability, whether levels of craving changed across and within days, and, finally, whether individual differences in craving variability predicted post-residential treatment relapse. Results: Preliminary analyses found acceptable levels of data entry compliance and reliability. Consistent with expectations, craving varied both between (46%) and within persons, with most within-person variance (over 40%) existing within days. Other patterns that emerged indicated that, on average, craving declined across the 12-days of assessment, and was generally strongest at mid-day. Analyses also found that patients' person-level craving variability predicted post-treatment relapse, above and beyond their mean levels of craving. Conclusion: Analyses support the reliability, sensitivity, and potential utility of the 4x-day, 12-day assessment protocol for measuring craving during residential treatment.

The Pennsylvania Longitudinal Study of Parents and Children (PALSPAC) Twin Registry.

The Pennsylvania Longitudinal Study of Parents and Children Twin Registry was developed to capture a representative sample of multiple births and their parents in the state of Pennsylvania. The registry has two main efforts. The first began in 2012 through recruitment of adolescents in Pennsylvania schools. The second effort began in January 2019 in partnership with the Pennsylvania Department of Health to capture the birth cohort of twins born from 2007 to 2017. Study recruitment, sample demographics, focus and measures are provided, as well as future directions.

Developmental Change in Adolescent Delinquency: Modeling Time-Varying Effects of a Preventative Intervention and GABRA2 Halpotype Linked to Alcohol Use.

Better integrating human developmental factors in genomic research is part of a set of next steps for testing gene-by-environment interaction hypotheses. This study adds to this work by extending prior research using time-varying effect modeling (TVEM) to evaluate the longitudinal associations between the PROSPER preventive intervention delivery system, a GABRA2 haplotype linked to alcohol use, and their interaction on adolescent delinquency. Logistic and Poisson analyses on eight waves of data spanning ages 11 to 19 (60% female, 90% Caucasian) showed the intervention reduced delinquency from ages 13 to 16. Moreover, interaction analysis revealed that the effect of the multicomponent intervention was significantly greater for T-allele carriers of the GABRA2 SNP rs279845, but only during the 13 to 16 age period. The results are discussed in terms of adolescent delinquency normativeness, implications for preventive intervention research, and the utility of incorporating development in GxE research.

Romantic Partner Alcohol Misuse Interacts with GABRA2 Genotype to Predict Frequency of Drunkenness in Young Adulthood.

Previous research has identified the importance of romantic partners-including spouses, significant others, and dating partners-for influencing the engagement in health-risking behaviors, such as alcohol misuse during emerging adulthood. Although genetic factors are known to play a role in the development of young adult alcohol misuse, little research has examined whether genetic factors affect young adults' susceptibility to their romantic partners' alcohol misusing behaviors. The current study tests whether a single nucleotide polymorphism in the GABRA2 gene (rs279845) moderates the relationship between romantic partner alcohol misuse and frequency of drunkenness in young adulthood. Results revealed differential risk associated with romantic partner alcohol misuse and young adult drunk behavior according to GABRA2 genotype, such that individuals with the TT genotype displayed an elevated risk for frequency of drunkenness when romantic partner alcohol misuse was also high (IRR = 1.06, p ≤ 0.05). The findings demonstrate the potential for genetic factors to moderate the influence of romantic partners' alcohol misuse on drunk behavior during the transition to young adulthood.

Associations between alcohol dehydrogenase genes and alcohol use across early and middle adolescence: Moderation × Preventive intervention.

Data from the in-school sample of the PROSPER preventive intervention dissemination trial were used to investigate associations between alcohol dehydrogenase genes and alcohol use across adolescence, and whether substance misuse interventions in the 6th and 7th grades (targeting parenting, family functioning, social norms, youth decision making, and peer group affiliations) modified associations between these genes and adolescent use. Primary analyses were run on a sample of 1,885 individuals and included three steps. First, we estimated unconditional growth curve models with separate slopes for alcohol use from 6th to 9th grade and from 9th to 12th grade, as well as the intercept at Grade 9. Second, we used intervention condition and three alcohol dehydrogenase genes, 1B (ADH1B), 1C (ADH1C), and 4 (ADH4) to predict variance in slopes and intercept. Third, we examined whether genetic influences on model slopes and intercepts were moderated by intervention condition. The results indicated that the increase in alcohol use was greater in early adolescence than in middle adolescence; two of the genes, ADH1B and ADH1C, significantly predicted early adolescent slope and Grade 9 intercept, and associations between ADH1C and both early adolescent slope and intercept were significantly different across control and intervention conditions.

PROSPER Intervention Effects on Adolescents' Alcohol Misuse Vary by GABRA2 Genotype and Age.

Preventive intervention effects on adolescent alcohol misuse may differ based on genotypes in gene-by-intervention (G x I) interactions, and these G x I interactions may vary as a function of age. The current study uses a novel statistical method, time-varying effect modeling (TVEM), to test an age-varying interaction between a single nucleotide polymorphism in the GABRA2 gene (rs279845) and a preventive intervention in predicting alcohol misuse in a longitudinal study of adolescents (ages 11-20). The preventive intervention was PROSPER, a community-based system for delivery of family and school programs selected from a menu of evidence-based interventions. TVEM results revealed a significant age-varying GABRA2 x intervention interaction from ages 12 to 18, with the peak effect size seen around age 13 (IRR = 0.50). The intervention significantly reduced alcohol misuse for adolescents with the GABRA2 TT genotype from ages 12.5 to 17 but did not reduce alcohol use for adolescents with the GABRA2 A allele at any age. Differences in intervention effects by GABRA2 genotype were most pronounced from ages 13 to 16-a period when drinking is associated with increased risk for alcohol use disorder. Our findings provide additional evidence that intervention effects on adolescent alcohol misuse may differ by genotype, and provide novel evidence that the interaction between GABRA2 and intervention effects on alcohol use may vary with age. Implications for interventions targeting adolescent alcohol misuse are discussed.

Transactions Between Substance Use Intervention, the Oxytocin Receptor (OXTR) Gene, and Peer Substance Use Predicting Youth Alcohol Use.

This study investigated the oxytocin receptor (OXTR) gene's moderation of associations between exposure to a substance misuse intervention, average peer substance use, and adolescents' own alcohol use during the 9th-grade. OXTR genetic risk was measured using five single nucleotide polymorphisms (SNPs), and peer substance use was based on youths' nominated closest friends' own reports of alcohol, cigarette, and marijuana use, based on data from the PROSPER project. Regression models revealed several findings. First, low OXTR risk was linked to affiliating with friends who reported less substance use in the intervention condition but not the control condition. Second, affiliating with high substance-using friends predicted youth alcohol risk regardless of OXTR risk or intervention condition. Third, although high OXTR risk youth in the intervention condition who associated with low substance-using friends reported somewhat higher alcohol use than comparable youth in the control group, the absolute level of alcohol use among these youth was still among the lowest in the sample.

Twelve Steps, Two Factors: Coping Strategies Moderate the Association Between Craving and Daily 12-Step Use in a College Recovery Community.

BACKGROUND: Affiliating with 12-step groups appears to reduce relapse risk. By relying on between-person designs, extant research has been unable to examine daily mechanisms through which 12-step group affiliation contributes to recovery. OBJECTIVES: To examine the daily use and factor structure of the 12 steps and intrapersonal predictors and moderators of 12-step use. To determine whether the 12 steps were used in response to daily craving and, if so, which steps and in what contexts. METHODS: Data comprised 1304 end-of-day diary data entries from 55 young adults collected in 2008 from members of a college recovery community, combined with person-level baseline measures. Exploratory factor analysis examined the factor structure, and multi-level models examined both day-level and person-level predictors and moderators of step use, including meeting attendance, drug and alcohol dependence, social support, and coping strategies. RESULTS: Analyses produced two factors: Everyday steps, comprising surrender and maintenance steps, and action steps. Moderation analyses revealed that only action steps were significantly associated with craving, suggesting that craving can spur their use, but only among individuals pursuing certain general strategies for coping with stress: Separate median-split models produced significant associations between craving and action steps only among individuals high in avoidance, high in support-seeking, and/or low in problem-solving. Conclusions/Importance: This is the first study to empirically discern a 2-factor structure underlying the 12 steps, and to show that the two sets of steps are used in different contexts. The study also illustrates the value of person-centered approaches to recovery research and practice.

Extending Previous cG×I Findings on 5-HTTLPR's Moderation of Intervention Effects on Adolescent Substance Misuse Initiation.

This study addresses replication in candidate gene × environment interaction (cG×E) research by investigating if the key findings from Brody, Beach, Philibert, Chen, and Murry (2009) can be detected using data (N = 1,809) from the PROSPER substance use preventive intervention delivery system. Parallel to Brody et al., this study tested the hypotheses that substance misuse initiation would increase faster from age 11 to age 14 and be higher at age 14 among: (a) 5-HTTLPR short carrier adolescents versus long homozygotes, (b) control versus intervention adolescents, and (c) 5-HTTLPR short carriers in the control condition versus all other participants. The hypotheses were generally supported and results were consistent with Brody et al.'s cG×I finding. Results are discussed in light of replication issues in cG×E research and implications for intervention.

An Adolescent Substance Prevention Model Blocks the Effect of CHRNA5 Genotype on Smoking During High School.

INTRODUCTION: Prevention intervention programs reduce substance use, including smoking, but not all individuals respond. We tested whether response to a substance use prevention/intervention program varies based upon a set of five markers (rs16969968, rs1948, rs578776, rs588765, and rs684513) within the cluster of nicotinic acetylcholine receptor subunit genes (CHRNA5/A3/B4). METHODS: Participants (N = 424) were randomly assigned to either control condition, or a family-based intervention in grade 6 and a school-based drug preventive intervention in grade 7. Smoking in the past month was assessed in grades 9-12 using a four-point scale (0 = never smoked, 1 = smoked but not in last month, 2 = one or a few times, 3 = about once a week or more). RESULTS: There was a main effect of both the intervention (b = -0.24, P < .05) and genotype at rs16969968 (b = 0.14, P < .05) on high school smoking. Using dummy coding to allow for nonlinear effects, individuals with the A/A genotype smoked more often than those with G/G (b = 0.33, P < .05). A genotype × intervention effect was found with reduced smoking among those with A/A and G/A genotypes to levels similar to those with the G/G genotype (G/G vs. A/A: b = -0.67, P < .05; A/G vs. A/A: b = -0.61, P < .05; G/G vs. A/G ns). Results were nonsignificant for the other four markers. CONCLUSIONS: Preventive interventions can reduce the genetic risk for smoking from rs16969968.

The conditioning of intervention effects on early adolescent alcohol use by maternal involvement and dopamine receptor D4 (DRD4) and serotonin transporter linked polymorphic region (5-HTTLPR) genetic variants.

Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.

Differential genetic and environmental influences on developmental trajectories of antisocial behavior from adolescence to young adulthood.

Little research has investigated differential genetic and environmental influences on different developmental trajectories of antisocial behavior. This study examined genetic and environmental influences on liabilities of being in life-course-persistent (LCP) and adolescent-limited (AL) type delinquent groups from adolescence to young adulthood while considering nonviolent and violent delinquency subtypes and gender differences. A genetically informative sample (n = 356, 15-16 years) from the first three waves of In-Home Interview of the National Longitudinal Study of Adolescent to Adult Health was used, with 94 monozygotic and 84 dizygotic pairs of same-sex twins (50% male). Biometric liability threshold models were fit and found that the male-specific LCP type class, chronic, showed more genetic influences, while the AL type classes, decliner and desister, showed more environmental influences. Genetic liability and shared environment both influence the persistence of antisocial behavior. The development of female antisocial behavior appears to be influenced more by shared environment.

Differential Susceptibility: The Genetic Moderation of Peer Pressure on Alcohol Use.

Although peer pressure can influence adolescents' alcohol use, individual susceptibility to these pressures varies across individuals. The dopamine receptor D4 gene (DRD4) is a potential candidate gene that may influence adolescents' susceptibility to their peer environment due to the role dopamine plays in reward sensation during social interaction. We hypothesized that DRD4 genotype status would moderate the impact of 7th-grade antisocial peer pressure on 12th-grade lifetime alcohol use (n = 414; 58.7% female; 92.8% White). The results revealed significant main effects for antisocial peer pressure, but no main effects for DRD4 genotype on lifetime alcohol use. Adolescent DRD4 genotype moderated the association between peer pressure and lifetime alcohol use. For individuals who carried at least one copy of the DRD4 7-repeat allele (7+), antisocial peer pressure was associated with increased lifetime alcohol use. These findings indicate that genetic sensitivity to peer pressure confers increased alcohol use in late adolescence.

Developmental differences in early adolescent aggression: a gene × environment × intervention analysis.

Aggression-related problems such as assault and homicide among adolescents and young adults exact considerable social and economic costs. Although progress has been made, additional research is needed to help combat this persistent problem. Several lines of research indicate that parental hostility is an especially potent predictor of adolescent aggression, although most longitudinal research has focused on clarifying the direction of effects. In this study, we used longitudinal data from the PROSPER project (N = 580; 54.8% female), a primarily rural Caucasian preventative intervention sample, to examine developmental change in early- to mid-adolescent aggressive behavior problems (age 11-16 years). In addition, we examined maternal hostility as a predictor of developmental change in aggression and the PROSPER preventative intervention, designed to reduce substance use and aggression, as a potential influence on this association. Lastly, several studies indicate that variation in the DRD4 7-repeat gene moderates both parenting and intervention influences on externalizing behavior. Accordingly, we examined the potential moderating role of DRD4. As hypothesized, there was a significant maternal hostility by intervention interaction indicating that the intervention reduced the negative impact of maternal hostility on adolescent change in aggressive behavior problems. DRD4 7-repeat status (7+ vs. 7-) further conditioned this association whereby control group 7+ adolescents with hostile mothers showed increasing aggressive behavior problems. In contrast, aggression decreased for 7+ adolescents with similarly hostile mothers in the intervention. Implications for prevention are discussed as well as current perspectives in candidate gene-by-environment interaction research.

Predicting High School Minority Adolescents' Drinking from Their Exposure to White Schoolmates: Differences and Similarities among Hispanic, Black, and Asian U.S. Adolescents.

White students' drinking may constitute a risk factor for drinking among same-school minority adolescents. Our study examined data from 14,986 ethnic minority American high school students (56% female, mean age = 15.6). Models examined associations between school-level White student drinking and same-school Black, Hispanic, and Asian adolescents' drinking, as well as whether schools' proportions of White students and friendships with White schoolmates moderated these associations. Both school-level White students' drinking and minority students' friendships with White schoolmates were associated with levels of minority student drinking. But these associations were dependent upon levels of other study variables. In particular, there were higher associations between school-level risk factors and minorities' drinking when minority adolescents had high proportions of Whites among their friends.

The day-level effects of recovery community center attendance on indicators of recovery wellbeing and risk.

BACKGROUND: Recovery community centers (RCCs) are a relatively new resource in the recovery support landscape aimed at building their members' recovery capital. In recent years, interest in the value of RCCs has grown, however, no studies have used within-person methods to consider how RCCs may impact the day-to-day lives of their attendees. Using within-person data drawn from members of RCCs, this study examined how visiting RCCs was associated with several same-day indicators of recovery wellbeing and risk: daily sense of meaningfulness, recovery identity, negative affect, and positive affect. METHODS: Participants were 94 visitors of six RCCs in western Pennsylvania. Daily diary methods collected 10 nightly reports of daily RCC attendance and end-of-day meaningfulness, recovery identity, negative affect, and positive affect. Multilevel modeling accounted for nesting in the intensive longitudinal data. In independent models, the study regressed meaningfulness, recovery identity, negative affect, and positive affect onto day- and person-level RCC attendance. RESULTS: Within-person associations between RCC attendance and meaningfulness (b = 6.96, SE = 1.66, p < .001), recovery identity (b = 4.75, SE = 1.08, p < .001), and PA (b = 3.82, SE = 1.45, p < .01) were significant, although NA was not (b = -2.41, SE = 1.34, n.s.). All day- by person-level RCC attendance interactions (in preliminary models) and between-person associations were non-significant across recovery outcomes. CONCLUSIONS: The results indicated that on days participants visited RCCs, they reported significantly higher levels of meaningfulness, recovery identity, and positive affect, although negative affect levels did not significantly differ. Also, those who attended RCCs more frequently did not generally report different levels of recovery wellbeing and risk. Taken together, results suggest visiting RCCs works on a daily basis to support interpersonal processes related to positive recovery outcomes. That RCC visits do not appear to reduce negative affect suggests that additional programs may be needed to address negative affect. The within-person design provided insight into the dynamic processes that contribute to the intrapersonal states that support recovery and a practical approach to examining whether and how RCCs might support recovery. By using individuals as their own controls, the study design provided strong counterfactual inference.

Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.

BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.

Identifying gender-specific developmental trajectories of nonviolent and violent delinquency from adolescence to young adulthood.

Most research examining gender differences in developmental trajectories of antisocial behavior does not consider subtypes of antisocial behavior and is difficult to generalize due to small non-representative samples. The current study investigated gender difference in developmental trajectories from adolescence to young adulthood while addressing those limitations. Analyses were limited to respondents ages 15 and 16 in wave 1 (16-17 in wave 2, and 21-22 in wave 3) of the National Longitudinal Study of Adolescent Health (n = 6244, 49.5% males). Self-report nonviolent and violent delinquencies were simultaneously entered into latent class analysis. Four latent classes were identified: low, desister, decliner, and chronic (male-only). In addition to finding a male-specific chronic class, gender differences included differences in levels of nonviolent and violent delinquency between synonymous classes of males and females, and differences in prevalence of classes across genders. Neighborhood disadvantage and family support predicted trajectories.