Adult Alcohol Problems Research Articles

Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD.

Adolescent alcohol drinking is linked to high rates of adult alcohol problems and alcohol use disorder (AUD). The Neurobiology of Alcohol Drinking in Adulthood (NADIA) consortium adolescent intermittent ethanol (AIE) models adolescent binge drinking, followed by abstinent maturation to adulthood to determine the persistent AIE changes in neurobiology and behavior. AIE increases adult alcohol drinking and preference, increases anxiety and reward seeking, and disrupts sleep and cognition, all risks for AUD. In addition, AIE induces changes in neuroimmune gene expression in neurons and glia that alter neurocircuitry and behavior. HMGB1 is a unique neuroimmune signal released from neurons and glia by ethanol that activates multiple proinflammatory receptors, including Toll-like receptors (TLRs), that spread proinflammatory gene induction. HMGB1 expression is increased by AIE in rat brain and in post-mortem human AUD brain, where it correlates with lifetime alcohol consumption. HMGB1 activation of TLR increase TLR expression. Human AUD brain and rat brain following AIE show increases in multiple TLRs. Brain regional differences in neurotransmitters and cell types impact ethanol responses and neuroimmune gene induction. Microglia are monocyte-like cells that provide trophic and synaptic functions, that ethanol proinflammatory signals sensitize or "prime" during repeated drinking cycles, impacting neurocircuitry. Neurocircuits are differently impacted dependent upon neuronal-glial signaling. Acetylcholine is an anti-inflammatory neurotransmitter. AIE increases HMGB1-TLR4 signaling in forebrain, reducing cholinergic neurons by silencing multiple cholinergic defining genes through upregulation of RE-1 silencing factor (REST), a transcription inhibitor known to regulate neuronal differentiation. HMGB1 REST induction reduces cholinergic neurons in basal forebrain and cholinergic innervation of hippocampus. Adult brain hippocampal neurogenesis is regulated by a neurogenic niche formed from multiple cells. In vivo AIE and in vitro studies find ethanol increases HMGB1-TLR4 signaling and other proinflammatory signaling as well as reducing trophic factors, NGF, and BDNF, coincident with loss of the cholinergic synapse marker vChAT. These changes in gene expression-transcriptomes result in reduced adult neurogenesis. Excitingly, HMGB1 antagonists, anti-inflammatories, and epigenetic modifiers like histone deacetylase inhibitors restore trophic the neurogenesis. These findings suggest anti-inflammatory and epigenetic drugs should be considered for AUD therapy and may provide long-lasting reversal of psychopathology.

HEAVY DRINKING, MENTAL HEALTH PROBLEMS AND RECOVERY IN OLDER ADULTS: EXPLORING SUPPORT NEEDS

Abstract Many older adults who consume alcohol at harmful levels experience mental health problems. Common life events such as retirement, bereavement, and declining health, can contribute to anxiety and depression, with alcohol consumption being used as a coping mechanism. Tailored support is crucial to address the unique needs of older adults facing both alcohol misuse and mental health problems. These patients often fall into gaps between services (family practice/alcohol/mental health), which are unable to meet their complex support needs. This qualitative study aimed to understand the lived experiences of older adults with co-occurring heavy drinking and mental health problems, support received and unmet needs. We conducted semi-structured interviews with 14 older adults living in the North of England (completed Summer 2023). Thematic analysis and constant comparison were employed in data analysis. Findings highlighted the importance of age-tailored initiatives such as access to mental health support while actively drinking, supervised detoxification, increased peer support and services that are age inclusive and friendly. Risk factors such as grief, loneliness, financial problems and undiagnosed trauma in older adults contributed to development of these conditions. Older adults need services to work together, integrated around patient needs and addressing heavy drinking and mental health concerns at the same time. Future research should focus on improving mental health literacy and, developing holistic and preventive interventions to address risk factors for co-occurring alcohol and mental health problems in older adults.

Investigating the role of emotion regulation in the relationship between childhood trauma and alcohol problems in American Indian adults

ObjectiveTo investigate whether use of cognitive reappraisal and expressive suppression interact with childhood trauma burden to predict alcohol problems in a sample of American Indian adults. MethodsFour hundred and twenty-nine American Indian adults (Mean age = 37.62, 59.5 % male) completed an online survey to measure childhood trauma exposure, perceived impact of childhood trauma, trait use of expressive suppression, and alcohol problems in adulthood. ResultsTrait use of cognitive reappraisal and expressive suppression interacted with childhood trauma burden to predict alcohol problems in adulthood. American Indian adults who reported high levels of childhood trauma burden who also reported frequent use of both cognitive reappraisal and expressive suppression had significantly more alcohol problems compared to individuals who reported similarly high levels of childhood trauma burden who reported low use of these emotion regulation strategies. ConclusionsThese findings provide initial evidence that emotion regulation interventions which focus on different emotion regulation strategies could be an effective way to offset the risk for alcohol problems associated with childhood trauma.

Coping and Conformity Motives Mediate the Joint Effects of the Behavioral Inhibition and Approach Systems on Alcohol Problems in Young Adults

Background: Gray’s original Reinforcement Sensitivity Theory (RST) posits that an oversensitive behavioral inhibition system (BIS) may increase risk for negative-reinforcement-motivated drinking, given its role in anxiety. However, existing data provides mixed support for the BIS-alcohol use association. The inconsistent evidence is not surprising, as the revised RST predicts that the behavioral approach system (BAS) should moderate the effect of the BIS on alcohol use. A strong BAS is thought to bring attention to the negatively reinforcing effects of alcohol, leading to problem drinking among those with a strong BIS. While emerging results support this interaction, we still have much to learn about the mechanisms underlying this effect on alcohol use. Accordingly, we examined motives for alcohol use as mediators of the joint associations of the BIS and the BAS on drinking behaviors. Specifically, our central hypothesis was that individuals with a strong BIS and a strong BAS would endorse increased negative reinforcement motives for drinking (coping and conformity motives), which in turn would predict heavy drinking and alcohol problems. Method: Participants (N=346; 195 women) completed study measures as part of the baseline assessment for a larger study. Results: Overall, results partially supported the hypotheses. Mediated moderation analyses showed that the indirect effect of the BIS on alcohol problems, through coping and conformity motives, was strongest at high levels of the BAS. This effect was not supported for alcohol use. Conclusions: Our findings suggest that clinical interventions should target coping and conformity reasons for drinking among anxious, reward responsive, young adults.

Longitudinal co-trajectories of depression and alcohol problems in adults during the COVID-19 pandemic.

The online version contains supplementary material available at 10.1007/s12144-022-04109-4.

Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood.

Studies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage binge drinking avoid the human confounds and support lifelong changes that increase risks. AIE increases adult alcohol drinking, risky decision-making, reward-seeking, and anxiety as well as reductions in executive function that all increase risks for the development of an AUD. AIE causes persistent increases in brain neuroimmune signaling high-mobility group box 1 (HMGB1), Toll-like receptor, receptor for advanced glycation end products, and innate immune genes that are also found to be increased in human AUD brain. HMGB1 is released from cells by ethanol, both free and within extracellular vesicles, that act on neurons and glia, shifting transcription and cellular phenotype. AIE-induced decreases in adult hippocampal neurogenesis and loss of basal forebrain cholinergic neurons are reviewed as examples of persistent AIE-induced pathology. Both are prevented and reversed by anti-inflammatory and epigenetic drugs. Findings suggest AIE-increased HMGB1 signaling induces the RE-1 silencing transcript blunting cholinergic gene expression, shifting neuronal phenotype. Inhibition of HMGB1 neuroimmune signaling, histone methylation enzymes, and galantamine, the cholinesterase inhibitor, both prevent and reverse AIE pathology. These findings provide new targets that may reverse AUD neuropathology as well as other brain diseases linked to neuroimmune signaling. SIGNIFICANCE STATEMENT: Adolescent underage binge drinking studies find that earlier adolescent drinking is associated with lifelong alcohol problems including high levels of lifetime alcohol use disorder (AUD). Preclinical studies find the underage binge drinking adolescent intermittent ethanol (AIE) model causes lasting changes in adults that increase risks of developing adult alcohol problems. Loss of hippocampal neurogenesis and loss of basal forebrain cholinergic neurons provide examples of how AIE-induced epigenetic and neuroimmune signaling provide novel therapeutic targets for adult AUD.

Indirect effects of theory of mind on alcohol use and problems in underage drinkers: The role of peer pressure to drink

ObjectivePrior studies demonstrate a link between socio-cognitive deficits and alcohol problems in adolescents and young adults. Researchers have proposed that young people with such deficits may misperceive and over-value peers' attitudes about drinking and consider drinking a way to be accepted by their peer group. We test this hypothesis by investigating whether theory of mind (ToM) deficits in underage (18–20-year-old) drinkers are associated with binge drinking and alcohol problems, and whether these ToM deficits have an indirect effect on alcohol outcomes through perceived peer pressure to drink (i.e., high conformity motives and low perceived ability to refuse alcohol during social pressure). MethodParticipants (N = 472; 91 % female; 71 % White; Mage = 19.28 ± 0.77) were recruited from TurkPrime and completed measures assessing ToM, conformity motives, self-efficacy to resist peer pressure to drink, alcohol problems, and binge drinking. Bivariate correlations were run to examine associations between study variables. Indirect effect models were run in SPSS, using the PROCESS add-on, to assess the indirect effects of ToM on alcohol outcomes through conformity motives and self-efficacy to refuse peer pressure to drink. ResultsToM had indirect effects on binge drinking and alcohol problems through conformity motives (but not self-efficacy to resist peer pressure to drink). Lower ToM was associated with higher conformity motives, which were then associated with more frequent binge drinking and greater alcohol problems. ConclusionsThese findings highlight the role of social cognition in young adult alcohol misuse and suggest more work is needed to understand the potential influence of peer pressure in this association.

Exploring the relationships between adolescent alcohol misuse and later life health outcomes.

We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β=0.03, 95% CI [0.03, 0.04]), self-rated health (β=-0.02, 95% CI [-0.03, -0.01]), and life satisfaction (β=-0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.

Solitary alcohol use in adolescence predicts alcohol problems in adulthood: A 17-year longitudinal study in a large national sample of US high school students

BackgroundIdentifying risk factors for alcohol use disorder (AUD) is important for public health. The social context of drinking—such as drinking alone—may be an independent and robust early risk marker for AUD symptoms later in life. We evaluated whether solitary alcohol use in adolescence (age 18) and young adulthood (age 23/24) was concurrently associated with binge drinking and prospectively predicted age 35 AUD symptoms, and whether associations differed by sex. MethodsLongitudinal data were from the Monitoring the Future study. Surveys were completed by adolescents in 12th grade at age 18 (1976–2002), young adults at age 23/24 (1981–2008), and adults at age 35 (1993–2019). Analyses included past 12-month alcohol users (n = 4464 for adolescent models; n = 4561 for young adult models). Multivariable regression analyses tested whether adolescent and young adult solitary alcohol use was associated concurrently with binge drinking frequency and prospectively with age 35 AUD symptoms. ResultsSolitary alcohol use in adolescence and young adulthood was associated (a) concurrently with binge drinking and (b) prospectively with increased risk of age 35 AUD symptoms (even after controlling for earlier binge drinking, alcohol use frequency, and sociodemographic covariates). Adolescent solitary alcohol use was associated with age 35 AUD symptoms particularly among females; no interaction was observed between sex and young adult solitary alcohol use in predicting age 35 AUD symptoms. ConclusionsAdolescent and young adult solitary alcohol use was associated with increased adult AUD symptoms above and beyond other risk factors; adolescent female solitary alcohol users were especially at risk.

A brief young adult alcohol problems screening test: Short form development using combinatorics

Objective: To develop a shortened form of the Young Adult Alcohol Problems Screening Test 1 (YAAPST; original length = 27 items) using a novel combinatorial approach. Participants: 489 college freshmen, half of whom were above average risk for alcohol use disorder based upon family history, attending a large, Midwestern University followed prospectively for 16–17 years across 7 measurement occasions (waves). Methods: Using an exhaustive combinatorial approach, we evaluated all possible combinations of questions and questionnaire length. Each candidate short-form was evaluated using part-whole correlations, alpha coefficients, and polyserial correlations with DSM-III criteria. Results: The 12-item scale, the Brief-YAAPST, was chosen as the best candidate short-form as this scale had the fewest items while maintaining strong reliability and validity. Conclusions: Complete enumeration optimization effectively produced a 12-item short form with minimal loss of reliability and validity making the Brief-YAAPST a desirable assessment alternative when there are concerns about participant or client burden.

Binge Drinking and Alcohol Problems Among Moderate Average-Level Drinkers

A significant amount of binge drinking among adults escapes public health scrutiny because it occurs among individuals who drink at a moderate average level. This observational study examined the role of a binge pattern of drinking in predicting alcohol problems among moderate drinkers in a U.S. national sample of adults. Participants were 1,229 current drinkers aged ≥30 years from 2 waves of the study of Midlife Development in the United States, with a 9-year time lag (2004-2015) (analyzed in 2021‒2022). Negative binomial regression analyses were used to examine the number of alcohol problems, and binary logistic regression analyses were used to examine multiple (≥2) alcohol problems. Independent of the average level of drinking, binge drinking was linked with an almost 3 times increase in the number of concurrent alcohol problems and a 40% increase in the number of alcohol problems prospectively 9 years later. Moderate average level drinkers accounted for most cases of binge drinking and multiple alcohol problems. Among moderate drinkers, binge drinking was linked with a close to 5 times increase in concurrent multiple alcohol problems and a >2 times increase in multiple alcohol problems prospectively 9 years later. These results substantially broaden an increasing recognition that binge drinking is a public health concern among adults. Moderate average-level drinkers should be included in efforts to reduce alcohol problems in adults. These findings are applicable to primary and secondary prevention of alcohol problems with the potential to advance population health.

Exploration of the Impact of Combining Risk Phenotypes on the Likelihood of Alcohol Problems in Young Adults.

We tested the hypothesis that high novelty seeking (NS-an externalizing trait), sweet-liking (SL-a phenotype that may reflect processing of hedonic stimuli) and initial insensitivity to the impairing effects of alcohol (SRE-A) act independently and synergistically to increase the likelihood of having alcohol-related problems in young adults. A sample of 145 young adults, ages 18-26, balanced for gender and alcohol use disorders identification test (AUDIT) scores <8 or ≥8 were selected from a prior sample. NS, SL and SRE-A were assessed along with AUDIT score and family history of alcoholism (FH). The effect of phenotypes and their interaction on the likelihood of alcohol problems was assessed. All three phenotypes contribute to the total AUDIT score. The best-fitting model explaining 35.8% of AUDIT variance includes all three phenotypes and an interaction between NS and SL/sweet-disliking (SDL) status. The addition of FH to the model explains an additional 4% of variance in both models. Classification and regression tree analysis showed that the main phenotype influencing AUDIT score is NS. The SL/SDL phenotype is a strong modifying factor for high NS. SRE-A was shown to be a weak modifier for individuals with low NS. The evidence supports the hypothesis that the presence of multiple alcohol use disorders (AUD) risk phenotypes with different underlying neurobiological mechanisms within an individual (SL, NS and SRE-A) represents a higher likelihood for developing alcohol-related problems and may allow for a graded assessment of risk for AUD and offer the possibility for early intervention strategies.

Consequences of adolescent alcohol use on adult hippocampal neurogenesis and hippocampal integrity.

Alcohol is the most commonly used drug among adolescents. Their decreased sensitivity to self-regulating cues to stop drinking coincides with an enhanced vulnerability to negative outcomes of excessive drinking. In adolescents, the hippocampus is one brain region that is particularly susceptible to alcohol-induced neurodegeneration. While cell death is causal, alcohol effects on adult neurogenesis also impact hippocampal structure and function. This review describes what little is known about adolescent-specific effects of alcohol on adult neurogenesis and its relationship to hippocampal integrity. For example, alcohol intoxication inhibits neurogenesis persistently in adolescents but produces aberrant neurogenesis after alcohol dependence. Little is known, however, about the role of adolescent-born neurons in hippocampal integrity or the mechanisms of these effects. Understanding the role of neurogenesis in adolescent alcohol use and misuse is critical to our understanding of adolescent susceptibility to alcohol pathology and increased likelihood of developing alcohol problems in adulthood.

A systematic review and meta-analysis on the association between solitary drinking and alcohol problems in adults.

Background and aimsSolitary drinking in adolescents and young adults is associated with greater risk for alcohol problems, but it is unclear whether this association exists in older demographics. The current paper is the first meta‐analysis and systematic review, to our knowledge, to determine whether adult solitary drinking is associated with greater risk for alcohol problems.MethodsPsychINFO, PubMed and Google Scholar were searched following a pre‐registered International Prospective Register of Systematic Reviews (PROSPERO) protocol (CRD42019147075) and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methodology. Following the methodology used in our recent systematic review and meta‐analysis on adolescent/young adult solitary drinking, we systematically reviewed solitary drinking measures/definitions, prevalence rates and associated demographic variables in adults. We then meta‐analyzed (using random‐effects models) associations between adult solitary drinking and alcohol use/problems, negative affect and negative/positive reinforcement‐related variables (e.g. drinking to cope or for enhancement).ResultsSolitary drinking was defined as drinking while physically alone in nearly all studies, but measures varied. Prevalence rates were generally in the 30–40% range, with some exceptions. In general, males were more likely than females to report drinking alone, and married individuals were less likely than unmarried individuals to report drinking alone; racial/ethnic differences were mixed. Meta‐analytical results showed significant effects for the associations between solitary drinking and the following factors: alcohol consumption, r = 0.25, 95% confidence interval (CI) = 0.18, 0.33, k = 15, I 2 = 97.41; drinking problems, r = 0.15, 95% CI = 0.10, 0.21, k = 14, I 2 = 92.70; and negative reinforcement, r = 0.24, 95% CI = 0.14, 0.32, k = 11, I 2 = 89.77; but not positive reinforcement, r = 0.02, 95% CI = 0.06, 0.09, k = 8, I 2 = 76.18; or negative affect, r = 0.03, 95% CI = −0.02, 0.08, k = 8, I 2 = 52.06. Study quality moderated the association between solitary drinking and negative affect (β = −0.07, P < 0.01) such that lower‐quality studies were significantly associated with larger effect sizes. Study quality was generally low; the majority of studies were cross‐sectional.ConclusionsSolitary drinking appears to have a small positive association with alcohol problems.

Alcohol Availability, Cost, Age of First Drink, and Its Association with At-Risk Alcohol Use in Moshi, Tanzania.

The Kilimanjaro region has one of the highest levels of reported alcohol intake per capita in Tanzania. Age at first drink has been found to be associated with alcohol problems in adulthood, but there is less information on the age of first drink in the Kilimanjaro region and its associations with alcohol-related consequences later in life. Furthermore, local alcohol cost and availability may influence the prevalence of alcohol use and alcohol use disorders. Data on the age of first drink, alcohol use disorder identification tool (AUDIT), number and type of alcohol consequences (DrInC), and perceived alcohol at low cost and high availability for children and adolescents were collected from an alcohol and health behavior survey of injury patients (N=242) in Moshi, Tanzania. Generalized linear models were used to test age at first drink, perceived alcohol cost and availability, and their association with the AUDIT and DrInC scores, and current alcohol use, respectively. Consuming alcohol before age 18 was significantly associated with higher AUDIT and DrInC scores, with odds ratios of 1.22 (CI: 1.004, 1.47) and 1.72 (CI: 1.11, 2.63), respectively. Female gender is strongly associated with less alcohol use and alcohol consequences, represented by an odds ratio of 3.70 (CI: 1.72, 8.33) for an AUDIT score above 8 and an odds ratio of 3.84 (CI: 2.13, 6.67) with the DrInC score. Perceived high availability of alcohol for children is significantly related to higher alcohol use quantity, with the odds ratio of 1.6 (CI: 1.17, 2.20). The first use of alcohol before the age of 18 is associated with higher alcohol use and alcohol-related adverse consequences. In Tanzania, age at first drink is an important target for interventions aiming to prevent negative alcohol-related consequences later in life.

Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19.

Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19.

Does Adolescent Alcohol Harm Minimization Policy Exposure Reduce Adult Alcohol Problems? A Cross-National Comparison

PurposeAdolescent alcohol use carries risks for problem behaviors, such as injury and school dropout, as well as increases the risk of alcohol dependence later on, making public health approaches that curb youth alcohol use a key concern. The present study uses a two-state comparison of alcohol-related policies in Victoria, Australia and Washington State, U.S. (harm minimization in Australia and zero tolerance in the U.S.) to examine whether youth alcohol use in each state is related to alcohol-related problems in young adulthood. MethodsData were drawn from the International Youth Development Study (N = 1,965) that followed youth in Victoria and Washington states from age 13 years, with follow-up at ages 14 and 15 years, and then again at age 25 years. Multiple-group structural equation modeling was used to test whether early alcohol use was equally related to alcohol problems (measured by the Alcohol Use Disorder Identification Test) at age 25 years and whether the relationship was moderated by family and school environments that were tolerant of youth drinking and by gender. ResultsYouth in Victoria reported greater rates of alcohol use compared with youth in Washington, as well as more permissive family and school environments. Early alcohol use was equally associated with Alcohol Use Disorder Identification Test problems at age 25 years in the two nations, and none of the moderators significantly changed the association. ConclusionsResults suggest that harm minimization policies adopted in Victoria are less effective at reducing alcohol problems during young adulthood compared with the stricter zero-tolerance approaches adopted in Washington State.

Gender differences among adolescents with substance abuse problems at Maria clinics in Sweden.

Aim:The article describes similarities and differences regarding various risk factors between girls and boys with substance abuse problems who begin outpatient treatment at the Maria clinics in Sweden. Potential hypotheses and some implications are also discussed.Methods:This cross-sectional study was based on interview data from 2169 adolescents obtained over three years from outpatient clinics in 11 Swedish cities.Results:Girls appear to consistently have more difficult family and childhood environments than boys, and are more likely to have problems related to school, more serious substance abuse problems, and more severe mental health problems. Criminal activity is significantly higher among boys.Conclusions:The study shows that girls entering treatment generally have significantly more risk factors than boys and thus more extensive problems in several aspects of life, which in turn increases the risk of developing serious drug and alcohol problems in adulthood. The study supports the gender-paradoxical relationship in which a smaller proportion of girls than boys enter treatment for substance abuse, even though girls tend to have more problematic life situations.

Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems.

Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G×E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G×E effects. We examined these questions in the young adult FinnTwin12 sample (n=1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G×E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G×E effects in an interaction between romantic relationship status and intoxication frequency. Contrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G×E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency. These findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.

Adult Drug and Alcohol Problems, Children’s Needs, 2nd edn,Joy Barlow, Di Hart and Jane Powell

Adult Drug and Alcohol Problems, Children’s Needs, 2nd edn,Joy Barlow, Di Hart and Jane Powell