Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank.

BACKGROUND: In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGSAUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGSAUD would be negatively associated with remission. METHODS: Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history. RESULTS: In COGA EA, PGSAUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, ßs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGSAUD was positively associated with remission (p = 0.004, ß = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, ß = 0.15). CONCLUSIONS: PGSAUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.

Alcohol use polygenic risk score, social support, and alcohol use among European American and African American adults.

Alcohol use is influenced by genetic and environmental factors. We examined the interactive effects between genome-wide polygenic risk scores for alcohol use (alc-PRS) and social support in relation to alcohol use among European American (EA) and African American (AA) adults across sex and developmental stages (emerging adulthood, young adulthood, and middle adulthood). Data were drawn from 4,011 EA and 1,274 AA adults from the Collaborative Study on the Genetics of Alcoholism who were between ages 18-65 and had ever used alcohol. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism and provided saliva or blood samples for genotyping. Results indicated that social support from friends, but not family, moderated the association between alc-PRS and alcohol use among EAs and AAs (only in middle adulthood for AAs); alc-PRS was associated with higher levels of alcohol use when friend support was low, but not when friend support was high. Associations were similar across sex but differed across developmental stages. Findings support the important role of social support from friends in buffering genetic risk for alcohol use among EA and AA adults and highlight the need to consider developmental changes in the role of social support in relation to alcohol use.

Diagnostic Criteria for Identifying Individuals at High Risk of Progression From Mild or Moderate to Severe Alcohol Use Disorder.

Importance: Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) diagnoses of substance use disorders rely on criterion count-based approaches, disregarding severity grading indexed by individual criteria. Objective: To examine correlates of alcohol use disorder (AUD) across count-based severity groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether specific criteria within mild-to-moderate AUD differentiate across relevant correlates and manifest in greater hazards of severe AUD development. Design, Setting, and Participants: This cohort study involved 2 cohorts from the family-based Collaborative Study on the Genetics of Alcoholism (COGA) with 7 sites across the United States: cross-sectional (assessed 1991-2005) and longitudinal (assessed 2004-2019). Statistical analyses were conducted from December 2022 to June 2023. Main Outcomes and Measures: Sociodemographic, alcohol-related, psychiatric comorbidity, brain electroencephalography (EEG), and AUD polygenic score measures as correlates of DSM-5 AUD levels (ie, mild, moderate, severe) and criterion severity-defined mild-to-moderate AUD diagnostic groups (ie, low-risk vs high-risk mild-to-moderate). Results: A total of 13 110 individuals from the cross-sectional COGA cohort (mean [SD] age, 37.8 [14.2] years) and 2818 individuals from the longitudinal COGA cohort (mean baseline [SD] age, 16.1 [3.2] years) were included. Associations with alcohol-related, psychiatric, EEG, and AUD polygenic score measures reinforced the role of increasing criterion counts as indexing severity. Yet within mild-to-moderate AUD (2-5 criteria), the presence of specific high-risk criteria (eg, withdrawal) identified a group reporting heavier drinking and greater psychiatric comorbidity even after accounting for criterion count differences. In longitudinal analyses, prior mild-to-moderate AUD characterized by endorsement of at least 1 high-risk criterion was associated with more accelerated progression to severe AUD (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared with prior mild-to-moderate AUD without endorsement of high-risk criteria (aHR, 5.64; 95% CI, 3.28-9.70), independent of criterion count. Conclusions and Relevance: In this cohort study of a combined 15 928 individuals, findings suggested that simple count-based AUD diagnostic approaches to estimating severe AUD vulnerability, which ignore heterogeneity among criteria, may be improved by emphasizing specific high-risk criteria. Such emphasis may allow better focus on individuals at the greatest risk and improve understanding of the development of AUD.

COVID-19 pandemic stressors are associated with reported increases in frequency of drunkenness among individuals with a history of alcohol use disorder.

Some sources report increases in alcohol use have been observed since the start of the COVID-19 pandemic, particularly among women. Cross-sectional studies suggest that specific COVID-19-related stressful experiences (e.g., social disconnection) may be driving such increases in the general population. Few studies have explored these topics among individuals with a history of Alcohol Use Disorders (AUD), an especially vulnerable population. Drawing on recent data collected by the Collaborative Study on the Genetics of Alcoholism (COGA; COVID-19 study N = 1651, 62% women, age range: 30-91) in conjunction with AUD history data collected on the sample since 1990, we investigated associations of COVID-19 related stressors and coping activities with changes in drunkenness frequency since the start of the pandemic. Analyses were conducted for those without a history of AUD (N: 645) and three groups of participants with a history of AUD prior to the start of the pandemic: (1) those experiencing AUD symptoms (N: 606), (2) those in remission who were drinking (N: 231), and (3) those in remission who were abstinent (had not consumed alcohol for 5+ years; N: 169). Gender-stratified models were also examined. Exploratory analyses examined the moderating effects of 'problematic alcohol use' polygenic risk scores (PRS) and neural connectivity (i.e., posterior interhemispheric alpha EEG coherence) on associations between COVID-19 stressors and coping activities with changes in the frequency of drunkenness. Increases in drunkenness frequency since the start of the pandemic were higher among those with a lifetime AUD diagnosis experiencing symptoms prior to the start of the pandemic (14% reported increased drunkenness) when compared to those without a history of AUD (5% reported increased drunkenness). Among individuals in remission from AUD prior to the start of the pandemic, rates of increased drunkenness were 10% for those who were drinking pre-pandemic and 4% for those who had previously been abstinent. Across all groups, women reported nominally greater increases in drunkenness frequency when compared with men, although only women experiencing pre-pandemic AUD symptoms reported significantly greater rates of increased drunkenness since the start of the pandemic compared to men in this group (17% of women vs. 5% of men). Among those without a prior history of AUD, associations between COVID-19 risk and protective factors with increases in drunkenness frequency were not observed. Among all groups with a history of AUD (including those with AUD symptoms and those remitted from AUD), perceived stress was associated with increases in drunkenness. Among the remitted-abstinent group, essential worker status was associated with increases in drunkenness. Gender differences in these associations were observed: among women in the remitted-abstinent group, essential worker status, perceived stress, media consumption, and decreased social interactions were associated with increases in drunkenness. Among men in the remitted-drinking group, perceived stress was associated with increases in drunkenness, and increased relationship quality was associated with decreases in drunkenness. Exploratory analyses indicated that associations between family illness or death with increases in drunkenness and increased relationship quality with decreases in drunkenness were more pronounced among the remitted-drinking participants with higher PRS. Associations between family illness or death, media consumption, and economic hardships with increases in drunkenness and healthy coping with decreases in drunkenness were more pronounced among the remitted-abstinent group with lower interhemispheric alpha EEG connectivity. Our results demonstrated that only individuals with pre-pandemic AUD symptoms reported greater increases in drunkenness frequency since the start of the COVID-19 pandemic compared to those without a lifetime history of AUD. This increase was more pronounced among women than men in this group. However, COVID-19-related stressors and coping activities were associated with changes in the frequency of drunkenness among all groups of participants with a prior history of AUD, including those experiencing AUD symptoms, as well as abstinent and non-abstinent participants in remission. Perceived stress, essential worker status, media consumption, social connections (especially for women), and relationship quality (especially for men) are specific areas of focus for designing intervention and prevention strategies aimed at reducing pandemic-related alcohol misuse among this particularly vulnerable group. Interestingly, these associations were not observed for individuals without a prior history of AUD, supporting prior literature that demonstrates that widespread stressors (e.g., pandemics, terrorist attacks) disproportionately impact the mental health and alcohol use of those with a prior history of problems.

The collaborative study on the genetics of alcoholism: Sample and clinical data.

The collaborative study on the genetics of alcoholism (COGA) is a multi-site, multidisciplinary project with the goal of identifying how genes are involved in alcohol use disorder and related outcomes, and characterizing how genetic risk unfolds across development and in conjunction with the environment and brain function. COGA is a multi-generational family-based study in which probands were recruited through alcohol treatment centers, along with a set of community comparison families. Nearly 18,000 individuals from >2200 families have been assessed over a period of over 30 years with a rich phenotypic battery that includes semi-structured psychiatric interviews and questionnaire measures, along with DNA collection and electrophysiological data on a large subset. Participants range in age from 7 to 97, with many having longitudinal assessments, providing a valuable opportunity to study alcohol use and problems across the lifespan. Here we provide an overview of data collection methods for the COGA sample, and details about sample characteristics and comorbidity. We also review key research findings that have emerged from analyses of the COGA data. COGA data are available broadly to researchers, and we hope this overview will encourage further collaboration and use of these data to advance the field.

Genomic risk for post-traumatic stress disorder in families densely affected with alcohol use disorders.

Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 (N = 3533) and Million Veterans Program GWAS of PTSD (N = 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD (B = 0.126, p < 0.001), alcohol dependence (B = 0.231, p < 0.001), and cocaine dependence (B = 0.086, p < 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD (B = 0.090, p < 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.

Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features.

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except for some connections involving the anterior cingulate cortex, which were predominantly hypoconnected. Other significant contributing features were: (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past five years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past twelve months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive "uplift" life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity data collected ~18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict the alcohol-related memory problems that arise in later life.

Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder.

BACKGROUND: Parental divorce and discord are associated with poorer alcohol-related outcomes for offspring. However, not all children exposed to these stressors develop alcohol problems. Our objective was to test gene-by-environment interaction effects whereby children's genetic risk for alcohol problems modifies the effects of parental divorce and discord to predict alcohol outcomes. METHODS: The sample included European (EA; N = 5608, 47% male, Mage ~ 36 years) and African (AA; N = 1714, 46% female, Mage ~ 33 years) ancestry participants from the Collaborative Study on the Genetics of Alcoholism. Outcomes included age at initiation of regular drinking and lifetime DSM-5 alcohol use disorder (AUD). Predictors included parental divorce, parental relationship discord, and offspring alcohol problems polygenic risk scores (PRSALC ). Mixed effects Cox proportional hazard models were used to examine alcohol initiation and generalized linear mixed effects models were used to examine lifetime AUD. Tests of PRS moderation of the effects of parental divorce/relationship discord on alcohol outcomes were examined on multiplicative and additive scales. RESULTS: Among EA participants, parental divorce, parental discord, and higher PRSALC were associated with earlier alcohol initiation and greater lifetime AUD risk. Among AA participants, parental divorce was associated with earlier alcohol initiation and discord was associated with earlier initiation and AUD. PRSALC was not associated with either. Parental divorce/discord and PRSALC interacted on an additive scale in the EA sample, but no interactions were found in AA participants. CONCLUSIONS: Children's genetic risk for alcohol problems modifies the impact of parental divorce/discord, consistent with an additive model of diathesis-stress interaction, with some differences across ancestry.

Associations of parent-adolescent closeness with P3 amplitude, frontal theta, and binge drinking among offspring with high risk for alcohol use disorder.

BACKGROUND: Parents impact their offspring's brain development, neurocognitive function, risk, and resilience for alcohol use disorder (AUD) via both genetic and socio-environmental factors. Individuals with AUD and their unaffected children manifest low parietal P3 amplitude and low frontal theta (FT) power, reflecting heritable neurocognitive deficits associated with AUD. Likewise, children who experience poor parenting tend to have atypical brain development and greater rates of alcohol problems. Conversely, positive parenting can be protective and critical for normative development of self-regulation, neurocognitive functioning and the neurobiological systems subserving them. Yet, the role of positive parenting in resiliency toward AUD is understudied and its association with neurocognitive functioning and behavioral vulnerability to AUD among high-risk offspring is less known. Using data from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1256, mean age [SD] = 19.25 [1.88]), we investigated the associations of closeness with mother and father during adolescence with offspring P3 amplitude, FT power, and binge drinking among high-risk offspring. METHODS: Self-reported closeness with mother and father between ages 12 and 17 and binge drinking were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. P3 amplitude and FT power were assessed in response to target stimuli using a Visual Oddball Task. RESULTS: Multivariate multiple regression analyses showed that closeness with father was associated with larger P3 amplitude (p = 0.002) and higher FT power (p = 0.01). Closeness with mother was associated with less binge drinking (p = 0.003). Among male offspring, closeness with father was associated with larger P3 amplitude, but among female offspring, closeness with mother was associated with less binge drinking. These associations remained statistically significant with father's and mothers' AUD symptoms, socioeconomic status, and offspring impulsivity in the model. CONCLUSIONS: Among high-risk offspring, closeness with parents during adolescence may promote resilience for developing AUD and related neurocognitive deficits albeit with important sex differences.

Genetic nurture effects for alcohol use disorder.

We tested whether aspects of the childhood/adolescent home environment mediate genetic risk for alcohol problems within families across generations. Parental relationship discord and parental divorce were the focal environments examined. The sample included participants of European ancestry (N = 4806, 51% female) and African ancestry (N = 1960, 52% female) from the high-risk Collaborative Study on the Genetics of Alcoholism. Alcohol outcomes in the child generation included lifetime criterion counts for DSM-5 Alcohol Use Disorder (AUD), lifetime maximum drinks in 24 h, age at initiation of regular drinking, and age at first alcohol intoxication. Predictors in the parent generation included relationship discord, divorce, alcohol measures parallel to those in the child generation, and polygenic scores for alcohol problems. Parental polygenic scores were partitioned into alleles that were transmitted and non-transmitted to the child. The results from structural equation models were consistent with genetic nurture effects in European ancestry families. Exposure to parental relationship discord and parental divorce mediated, in part, the transmission of genetic risk for alcohol problems from parents to children to predict earlier ages regular drinking (ßindirect = -0.018 [-0.026, -0.011]) and intoxication (ßindirect = -0.015 [-0.023, -0.008]), greater lifetime maximum drinks (ßindirect = 0.006 [0.002, 0.01]) and more lifetime AUD criteria (ßindirect = 0.011 [0.006, 0.016]). In contrast, there was no evidence that parental alleles had indirect effects on offspring alcohol outcomes via parental relationship discord or divorce in the smaller number of families of African ancestry. In conclusion, parents transmit genetic risk for alcohol problems to their children not only directly, but also indirectly via genetically influenced aspects of the home environment. Further investigation of genetic nurture in non-European samples is needed.

Social processes during recovery: An expansion of Kelly and Hoeppner's biaxial formulation of recovery.

Recent conceptualizations frame addiction recovery as a complex process involving changes across behavioral, physical, psychological, and social domains. These broad conceptualizations can be difficult to apply directly to research, making detailed models of individual dimensions necessary to guide empirical work and subsequent clinical interventions. We used Kelly and Hoeppner's (2015) biaxial formulation of recovery as a basis for a detailed examination of social processes in recovery using social network approaches. We delineated how appraisal of situational risks and social network resources result in coping actions, and how repeated iterations of this process change a person's social recovery capital over time. In addition, we incorporated the experience of interpersonal trauma and structural oppression, and demonstrated how the model accommodates the complex issues often encountered during recovery. We present a measurable framework that can guide empirical testing of how social processes and social recovery capital change over time during recovery. The model presented here illuminates key factors in the recovery process that have the potential to support trauma- and social-network-informed interventions. We call for research that empirically tests this model in ways that will result in practical, trauma-informed social network interventions for people in recovery.

High Polygenic Risk Scores Are Associated With Early Age of Onset of Alcohol Use Disorder in Adolescents and Young Adults at Risk.

Background: Genome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations. Methods: A total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using receiver operating characteristic curves and by analysis of the distribution of PRS. Results: European ancestry subjects with higher than median PRSs were at greater risk for onset of AUD than subjects with lower than median PRSs (p = 3 × 10-7). Area under the curve for the receiver operating characteristic analysis peaked at 0.88 to 0.95 using PRS plus sex, family history, comorbid disorders, age at first drink, and peer drinking; predictive power was primarily driven by clinical variables. In this high-risk sample, European ancestry subjects with a PRS score in the highest quartile showed a 72% risk for developing AUD and a 35% risk of developing severe AUD (compared with risks of 54% and 16%, respectively, in the lowest quartile). Conclusions: Predictive power for PRSs in the extremes of the distribution suggests that these may have future clinical utility. Uncertainties in interpretation at the individual level still preclude current application.

The role of parental genotype in the intergenerational transmission of externalizing behavior: Evidence for genetic nurturance.

The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents' own externalizing polygenic scores. Mediation analysis indicated that parental externalizing psychopathology partly explained the effect of parental genotype on children's externalizing behavior. We also found evidence for evocative gene-environment correlation, whereby adolescent externalizing polygenic scores were associated with lower parent-child communication, less parent-child closeness, and lower parental knowledge, controlling for parental genotype. These effects were observed among participants of European ancestry but not African ancestry, likely due to the limited predictive power of polygenic scores across ancestral background. These results demonstrate that in addition to genetic transmission, genes influence offspring behavior through the influence of parental genotypes on their children's environmental experiences, and the role of children's genotypes in shaping parent-child relationships.

Alcohol use disorder, psychiatric comorbidities, marriage and divorce in a high-risk sample.

OBJECTIVE: To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. METHOD: Participants included European ancestry (EA; n = 4,045) and African ancestry (AA; n = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, Mage ∼ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score (PRS), and AUD comorbidities, including conduct or antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. RESULTS: Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HRs] 0.70-0.83, ps < 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66-0.82, ps < 0.05) and those with MDD were more likely to marry (HR = 1.34, ps < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (odds ratios [ORs] 1.59-2.21, ps < 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. CONCLUSIONS: In a high-risk sample, AUD was associated with reduced likelihood of marriage in EA and AA individuals and increased risk of divorce in EA individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Deriving a Measure of Social Recovery Capital From the Important People and Activities Instrument: Construction and Psychometric Properties.

AIM: This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). METHODS: The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. RESULTS: Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald's ω = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. CONCLUSION: The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.

Evaluating risk for alcohol use disorder: Polygenic risk scores and family history.

BACKGROUND: Early identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD. METHODS: We studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity. RESULTS: AUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ). CONCLUSIONS: Both PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.

Retrospectively assessed subjective effects of initial opioid use differ between opioid misusers with opioid use disorder (OUD) and those who never progressed to OUD: Data from a pilot and a replication sample.

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N = 14) and heroin-addicted individuals in treatment for OUD (N = 15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N = 25) and without OUD (N = 25) who were assessed as part of an ongoing genetic study. We observed similar significant between-group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD.

The associations between polygenic risk, sensation seeking, social support, and alcohol use in adulthood.

Genetic predispositions play an important role in alcohol use. Understanding the psychosocial mechanisms through which genetic risk unfolds to influence alcohol use outcomes is critical for identifying modifiable targets and developing prevention and intervention efforts. In this study, we examined the role of sensation seeking and social support from family and friends in linking genetic risk to alcohol use. We also examined the role of social support in moderating the associations between genetic risk and sensation seeking and alcohol use. Data were drawn from a sample of 2,836 European American adults from the Collaborative Study on the Genetics of Alcoholism (46% male, mean age = 35.65, standard deviation [SD] = 10.78). Results from path analysis indicated that genome-wide polygenic scores for alcohol consumption (alc-GPS) were associated with higher sensation seeking, which in turn was associated with higher levels of alcohol use. alc-GPS was also associated with higher alcohol use indirectly via lower levels of family support. In addition, high friend support attenuated the association between alc-GPS and sensation seeking and alcohol use. The pattern of associations was similar for males and females, with some differences in the associations between social support and alcohol use observed across age. Our findings highlight the important role of intermediate phenotypes and gene-environment interplay in the pathways of risk from genetic predispositions to complex alcohol use outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Temporal trends in smoking and nicotine dependence in relation to co-occurring substance use in the United States, 2005-2016.

BACKGROUND: Despite an overall decline in tobacco use in the United States, secular trends of smoking and nicotine dependence with co-occurring substance use are not well characterized. METHODS: We examined self-reported tobacco and other substance use in 22,245 participants age 21-59 in the United States from six waves of the National Health and Nutrition Examination Survey (NHANES). Using Joinpoint regression, we assessed secular trends of smoking and nicotine dependence as a function of co-occurring use of alcohol, prescription opioids, marijuana/hashish, cocaine/heroin/methamphetamine, or other injection drug use. Multivariable logistic regressions were fitted to identify the potential risk factors. RESULTS: During 2005-2016, the prevalence of current smoking decreased (without co-occurring substance use: 17.0 %-12.7 %; with co-occurring use of one substance: 35.3 % to 24.6 %; with co-occurring use of two or more substances: 53.8 %-42.2 %), and moderate-to-severe nicotine dependence decreased as well (8.0 %-4.2 %, 16.0 %-8.8 %, and 23.9 %-15.7 %, respectively). Smoking and nicotine dependence were more likely in those with co-occurring use of one substance (current smoking: odds ratio [OR] = 2.22, 95 % confidence interval [CI] = 2.01-2.45); nicotine dependence: OR = 1.88, 95 % CI = 1.63-2.17) and in those with co-occurring use of two or more substances (current smoking: OR = 5.25, 95 % CI = 4.63-5.95; nicotine dependence: OR = 3.24, 95 % CI = 2.72-3.87). CONCLUSIONS: Co-occurring substance use was associated with smaller reductions in tobacco use, over time, and with increased odds of nicotine dependence. This suggests that co-occurring substance users should be regarded as a tobacco-related disparity group and prioritized for tobacco control interventions.