Alcohol Consumption Questionnaire: Scale development in a sample of Mexican American young adults and association with ADH7.

BACKGROUND: To understand why some individuals who develop alcohol use disorders (AUD) first begin to drink heavily, a number of scales have been developed that index aspects of alcohol craving and restraint from drinking. We developed a new measure called the Alcohol Consumption Questionnaire (ACQ), based in part on items modified from scales used to index binge eating because there are data to suggest that binge eating and binge drinking may share common antecedents. We present an initial validity study using data from a sample of Mexican Americans. METHODS: Data were from 699 Mexican American young adults in San Diego County, CA. A subsample (n=60) had short-term test-retest data. Factor analysis and reliability assessment guided item reduction. Item response theory (IRT) analyses quantified item severity and identified questions with differential item functioning (DIF). Logistic regression assessed associations of mean scale scores with AUD, adjusting for key demographics, alcohol expectancies and subjective response to alcohol. We also examined associations with a protective genetic variant downstream from the alcohol dehydrogenase 7 gene (ADH7). RESULTS: The scale was reduced from 20 to 14 questions, which can be summarized by a single overall score (Cronbach's alpha=0.896) or by two sub-scores (Consumption: 12 items, Cronbach's alpha=0.896; Enjoyment: 2 items, Cronbach's alpha=0.780). Test-retest reliability was very high (0.80-0.98) in this sample. The overall ACQ score and each subdomain score were strongly associated with AUD (ORs= 5.95 mild; 11.41 moderate; 48.56 severe) and family history of AUD. Respondents with the protective genetic variant had significantly lower overall ACQ scores (p<.001). CONCLUSION: The ACQ is a novel measure of alcohol consumption with strong relationships with both the AUD phenotype and ADH7 gene variants in a sample of Mexican American young adults.

Social zeitgeber and sleep loss as risk factors for suicide in American Indian adolescents.

American Indians / Alaska Natives (AI/AN) bear a high burden of suicide, the reasons for which are not completely understood, and rates can vary by tribal group and location. This article aims to identify circumstances reported by a community group of American Indian adolescent participants to be associated with their depression and/or suicide. American Indian adolescents (n = 360) were recruited from contiguous reservations and were assessed with a semi-structured diagnostic interview. Twenty percent of the adolescents reported suicidal thoughts (ideation, plans), an additional 8% reported a history of suicide attempts, and three deaths due to suicide were reported. Suicidal behaviors and major depressive disorder (MDD) co-occurred and were more common among female adolescents. The distressing events that adolescents most often reported were: death in the family, family disruption, peer relationship problems, and school problems. All of these events were significantly associated with suicidal behaviors, however those with suicidal acts were more likely to report death in the family. Those with MDD but no suicidal behaviors were more likely to report disruptions in the family. Disruptions in falling asleep were also associated with suicidal behaviors and having experienced a death in the family. Disruptions in important relationships, particularly through death or divorce, may be interpreted as a loss or disruption in "social zeitgebers" that may in turn disturb biological rhythms, such as sleep, thus potentially increase the risk for MDD and/or suicide. Prevention programs aimed at ameliorating the impact of disruptions in important relationships may potentially reduce suicidal behaviors in AI/AN adolescents.

Genetic factors associated with suicidal behaviors and alcohol use disorders in an American Indian population.

American Indians (AI) demonstrate the highest rates of both suicidal behaviors (SB) and alcohol use disorders (AUD) among all ethnic groups in the US. Rates of suicide and AUD vary substantially between tribal groups and across different geographical regions, underscoring a need to delineate more specific risk and resilience factors. Using data from over 740 AI living within eight contiguous reservations, we assessed genetic risk factors for SB by investigating: (1) possible genetic overlap with AUD, and (2) impacts of rare and low-frequency genomic variants. Suicidal behaviors included lifetime history of suicidal thoughts and acts, including verified suicide deaths, scored using a ranking variable for the SB phenotype (range 0-4). We identified five loci significantly associated with SB and AUD, two of which are intergenic and three intronic on genes AACSP1, ANK1, and FBXO11. Nonsynonymous rare and low-frequency mutations in four genes including SERPINF1 (PEDF), ZNF30, CD34, and SLC5A9, and non-intronic rare and low-frequency mutations in genes OPRD1, HSD17B3 and one lincRNA were significantly associated with SB. One identified pathway related to hypoxia-inducible factor (HIF) regulation, whose 83 nonsynonymous rare and low-frequency variants on 10 genes were significantly linked to SB as well. Four additional genes, and two pathways related to vasopressin-regulated water metabolism and cellular hexose transport, also were strongly associated with SB. This study represents the first investigation of genetic factors for SB in an American Indian population that has high risk for suicide. Our study suggests that bivariate association analysis between comorbid disorders can increase statistical power; and rare and low-frequency variant analysis in a high-risk population enabled by whole-genome sequencing has the potential to identify novel genetic factors. Although such findings may be population specific, rare functional mutations relating to PEDF and HIF regulation align with past reports and suggest a biological mechanism for suicide risk and a potential therapeutic target for intervention.

Comorbidity of anxiety/affective, conduct/antisocial, attention deficit, and alcohol use disorders with suicidal behaviors in an American Indian community sample of adults and adolescents.

AIMS: To study the associations of anxiety/affective disorders, conduct/antisocial disorders (ASPD/CD), attention deficit disorders (ADHD), and alcohol use disorders (AUD) with suicidal behaviors in an American Indian (AI) community sample of adolescents and adults. METHODS: Participants were AI (360 adolescents, 925 adults) recruited from reservations who were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). RESULTS: Among AI adults (mean age = 33 years), 17% percent reported lifetime experiences of suicidal thoughts (ideation and/or plans) and 14% reported suicidal acts (including either a suicide attempt history or verified death by suicide; n = 19 deaths). Among AI adolescents (mean age = 15 years), 20% experienced suicidal thoughts and 9% experienced suicidal acts (including 3 deaths). In logistic regression analyses, suicidal thoughts were significantly associated with lifetime diagnoses of affective disorder, CD and ADHD in adolescents, and with anxiety disorder, affective disorder, and ASPD/CD in adults. Suicidal acts were associated with affective disorder, ADHD, and alcohol drinking in adolescents and with anxiety disorder, ASPD/CD and AUD in adults. The number of comorbid disorders greatly increased the risk of both suicidal thoughts and acts among both adolescents and adults. CONCLUSIONS: In addition to affective disorders, both ADHD and CD in adolescents, and ASPD in adults, demonstrated an association with suicidal thoughts. Alcohol use by adolescents and AUD among adults also were associated with suicidal attempts in this AI sample. These findings suggest need for additional research and potential integration of alcohol in screening and intervention programs focused on the prevention of suicide among AI.

Event-related Oscillations to Emotional Faces are Related to a History of Internalizing Disorders.

Event-related oscillations (EROs) may represent sensitive biomarkers or endophenotypes for disorders that underlie risk behaviors such as suicidal thoughts and actions. In this study, young adults of American Indian (AI) (n = 821) and Mexican American (MA) (n = 721) ancestry (age 18-30 yrs) were clinically assessed for internalizing and externalizing disorders, and an internalizing scale was generated by extracting core diagnostic items from 6 lifetime DSM5-compatible diagnoses (social phobia, panic disorder, agoraphobia, obsessive compulsive disorder, post-traumatic stress disorder, major depressive episode) and symptoms of suicidality. EROs were generated to sad, happy and neutral faces, and energy and phase locking of delta ERO oscillations were assessed in frontal areas. An increase in delta ERO energy was found in the frontal lead (FZ) following presentation of the sad facial expressions in those with a history of 10 or more internalizing symptoms compared to those with no symptoms. Increases in delta ERO energy in FZ were also associated with a diagnosis of major depressive disorder (MDD), but not with anxiety disorders or antisocial personality disorder/conduct disorders (ASP). Major depression was also associated with increases in cross-cortical phase-locking (FZ-PZ). A decrease in the percentage of correctly identified neutral faces also was seen among those with 10 or more internalizing symptoms compared to those without internalizing symptoms, and in those with anxiety disorders, but not in those with ASP or MDD as compared to their controls. These findings suggest ERO measures may represent important potential biomarkers of depressive disorders as well as risk indicators for suicidal behaviors.

Trauma, historical trauma, PTSD and suicide in an American Indian community sample.

AIMS: To study the associations between perceived historical trauma, current traumatic events, diagnoses of post-traumatic stress disorder (PTSD), and suicidal behaviors in an American Indian community sample. METHODS: Participants were American Indians recruited from reservations who were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), as well as the Historical Loss Scale, Historical Loss Associated Symptoms Scale, and Stressful Life Events Scale. RESULTS: In data from 447 American Indian adults (mean age = 33 years), twenty percent reported lifetime experiences of suicidal thoughts (ideation and/or plans) and 14% reported suicidal acts, (including either a suicide attempt history or verified death by suicide (n = 4)). Diagnosis of PTSD and experience of assaultive trauma were each significantly associated with suicidal thoughts and acts, although assaultive trauma did not remain significant in models adjusting for gender and PTSD. High endorsement of symptoms associated with historical trauma was significantly associated with suicidal acts, and this remained significant when adjusting for gender and PTSD. CONCLUSIONS: PTSD and historical trauma have an association with suicide and suicidal attempts in this American Indian community. Although further research is needed to evaluate the causal nature of these relations, these findings suggest treatment and prevention programs for American Indian suicide may benefit from addressing issues related to feelings of historical losses, PTSD, and their associated symptomatology.

Age of onset and alcohol and cannabis use disorders among Mexican American young adults: Robust substance-specific effects of early use as a risk factor.

We investigated the substance-specific and cross-substance risk associated with early onset (before age 15) of drunkenness and cannabis use in the subsequent development of alcohol (AUD) and cannabis use disorder (CUD) in Mexican American young adults. Survival analyses employed Cox proportional hazards models for AUD and CUD, separately. In cross-risk analyses, we modeled estimates for those participants reporting lifetime use of both substances. Early onset of drunkenness and early onset of cannabis use were associated with shorter time to AUD and CUD, respectively, even after accounting for psychiatric disorders. While there were no cross-risk associations, adjusting for psychiatric disorders and early onset cannabis use attenuated the association of early drunkenness with AUD.

The clinical course of antisocial behaviors in men and women of three racial groups.

AIMS: To describe the clinical course and symptom profile of DSM-IV Antisocial Personality Disorder (ASPD) and the syndrome of Adult Antisocial Behavior Syndrome (AABS) and determine if they differ based on sex and race. METHODS: Using questions from a validated semi-structured interview, data were gathered from 2 independent family studies in: 1) American Indians (AI), and 2) European Americans (EA), African Americans (AA) (total n = 7171) who reported antisocial symptoms. RESULTS: Within these two samples 1148 (16%) individuals met ASPD criteria, 1932 (27%) met adult ASPD but not childhood conduct disorder (CD) (i.e., AABS). The clinical course of the antisocial behaviors studied did not differ based on race or sex; however, individual symptom counts, and age of onsets of those symptoms, were significantly different across the groups. Women reported fewer symptoms and at an older age (less fights, school suspensions/expulsions, arrests or jail time), than men but were more likely to run away from home. Those with ASPD vs. AABS had more symptoms overall including not experiencing remorse. AA and AI participants and those with ASPD, had more symptoms, and were more likely to be suspended/expelled from school and arrested at a younger age than EA. CONCLUSION: In these select samples, the order and sequence of antisocial behaviors did not differ by race, AASB vs. ASPD, or sex; however individual symptom endorsement did, with men (vs. women), those with ASPD (vs. AABS), AI and AA (vs. EA) reporting more suspensions/expulsions from school and arrests. This suggests further study of the possible role of race and sex in the consequences associated with antisocial syndromes is warranted.

Extreme Binge Drinking During Adolescence: Associations With Subsequent Substance Use Disorders in American Indian and Mexican American Young Adults.

OBJECTIVE: This study collected retrospective data on adolescent binge drinking (ABD) (5 drinks for boys, 4 for girls per occasion at least once per month) and/or extreme adolescent binge drinking (EABD) (10 or more drinks per occasion at least once per month) and tested for associations with demographic and diagnostics variables including alcohol and other substance use disorders (AUD/SUD). METHODS: Cross-sectional data were collected from young adult (age 18-30 yrs) American Indians (AI) (n = 534) and Mexican Americans (MA) (n = 704) using a semi-structured diagnostic instrument. RESULTS: Thirty percent (30%) of the sample reported ABD and 21% reported EABD. Those having had monthly ABD were more likely to be AI and have less education; those having had EABD were more likely to be AI, male, younger, have less education and lower economic status compared to participants without ABD. ABD/EABD was associated with higher impulsivity, a family history of AUD, and lower level of response to alcohol (ORs = 1.0-2.0), as well as with adult AUD (ORs = 3.7-48), other substance use disorders (ORs = 3.5-9), and conduct disorder/ antisocial personality disorder (ORs = 2.0-2.6), but not with anxiety/depression. Monthly EABD further increased the odds of AUD/SUD. CONCLUSIONS: Although binge drinking was more common in AI compared to MA, there were little effects of race in individual risk factor analyses. Monthly ABD and EABD were common among these AI/MA as adolescents, and, as with other ethnic groups, these drinking patterns resulted in highly significant increases in the odds of developing alcohol and other substance use disorders in young adulthood.

Effects of genetic risk for alcohol dependence and onset of regular drinking on the progression to alcohol dependence: A polygenic risk score approach.

BACKGROUND: Prior studies have established the importance of genetic contributions to the etiology of alcohol dependence (AD), and suggested an early onset of alcohol use represents an initial marker of this genetic risk, which is associated with a more rapid progression to AD and increased risk for AD itself. Building on prior work, the current study examined whether the additive effects of AD risk variants predicted the rate of progression to AD from the onset of regular drinking, a drinking milestone with high clinical relevance to AD prevention. METHODS: Data from 1501 European-ancestry adults from the University of California - San Francisco Family Alcoholism Study were used to examine whether polygenic risk scores for AD (PRSAD) and age-at-onset of regular drinking contributed uniquely to the likelihood of having a lifetime AD diagnosis and the rate of progression from regular drinking to AD. Mixed effects logistic regression and Cox proportional hazards regression analyses were employed. RESULTS: Increases in PRSAD were associated with a faster progression from regular drinking to AD independent of age-at-onset of regular drinking. An independent effect of age-at-onset of regular drinking was also observed indicating that a one-year delay in regular drinking was associated with a 7% decrease in the hazard of progression to AD among drinkers with an early onset (≤ 18), but a 3% increase among drinkers with a late onset (> 18) of regular drinking. CONCLUSIONS: These results broaden our understanding of the contributions of measured genotypes underlying AD-risk on the etiology and clinical course of AD.

Childhood Experiences and High-Intensity Drinking Among American Indian and Alaska Native Adults: Findings From the 2000-2015 National Alcohol Surveys.

OBJECTIVE: The purpose of this study was to examine associations with high-intensity drinking (HID) in American Indian/Alaska Native (AI/AN) populations and compare them to White and other minority groups using four National Alcohol Surveys, 2000 to 2015 (total N = 29,571; AI/ANs = 434). METHOD: Current drinking and HID (8+ and 12+ drinks on any day) from maximum drinks in the prior 12 months were analyzed with independent variables and race/ethnicity (AI/AN, non-Hispanic White, and other racial/ethnic groups combined). Adjusted logistic regression models comprised gender, age, marital status, employment, education, survey year, rurality, and especially, childhood trauma (physical/sexual abuse), and biological family alcohol problem history (each dichotomous). RESULTS: In adjusted population models, Whites had twice the odds of current drinking as AI/ANs, with no difference between other racial/ethnic groups and AI/ANs. Descriptively, AI/AN drinkers consumed at higher intensity levels than other groups, with higher prevalence of childhood trauma and family problem drinking than others. However, on a population basis, adjusting for all factors, apparent differences between AI/AN and White HID were eliminated; other minority groups together, compared with AI/ANs, showed lower odds of consuming 8+ drinks. CONCLUSIONS: AI/ANs had a higher prevalence of childhood trauma and family alcohol problems as well as lower current drinking likelihood compared with Whites. In adjusted population models, the combined other minorities group was less likely to ever consume 8+ drinks than AI/ANs. In all populations, childhood trauma and family alcohol problems increased the risk of HID, strongly so in AI/ANs. Addressing childhood trauma and family problems is important among AI/ANs to break generational cycles of drinking extreme amounts per occasion.

Delta Event-Related Oscillations Are Related to a History of Extreme Binge Drinking in Adolescence and Lifetime Suicide Risk.

Alcohol exposure typically begins in adolescence, and heavy binge drinking is associated with health risk behaviors. Event-related oscillations (EROs) may represent sensitive biomarkers or endophenotypes for early alcohol exposure as well as other risk behaviors such as suicidal thoughts and actions. In this study, young adults (age 18-30 years) of American Indian (AI) (n = 479) and Mexican American (MA) (n = 705) ancestry were clinically assessed, and EROs were generated to happy, sad and neutral faces. Extreme adolescent binge drinking (10+ drinks) was common (20%) in this population of AI/MA and associated with a significantly increased risk of a lifetime history of suicidal acts (SA, suicide attempts, deaths) but not suicidal thoughts (ST, ideation, plans). ST were reported among MA participants, whereas SA were more common among AI young adults. Extreme adolescent binge drinking was also associated with errors in detection of sad and neutral faces, increases in delta ERO energy, and decreases in phase locking (PL), particularly in parietal areas. A lifetime history of ST was associated with increases in delta ERO energy and PL, whereas SA were associated with decreases in both. These studies suggest that ERO measures may represent important potential biomarkers of adolescent extreme binge drinking and risk for suicidal behaviors.

Community Awareness of Outreach Efforts to Reduce Underage Drinking on California Indian Reservations.

We report an evaluation of a combined individual- and community-level treatment and prevention effort to reduce underage drinking by American Indian (AI) youths on rural California Indian reservations. The interventions included: brief motivational interviewing and psychoeducation for Tribal youths, restricting alcohol sales to minors in alcohol sales outlets, and community mobilization and awareness activities. Surveys were collected from 120 adults and 74 teens to evaluate the awareness and effectiveness of the interventions. A high proportion of adult (93%) and youth (96%) respondents endorsed being aware of one or more of the intervention activities, and 88% of adults and 71% of youth felt the program impacted the community in a positive way. Eighty-four percent of adults and 63% of youth agreed that as a result of the activities that they decided to take action to reduce teen drinking in their community. Being aware of more of the intervention activities significantly increased the odds of taking action to change drinking behaviors. This study documents that a significant proportion of the community was aware of the intervention efforts and that awareness caused them to take action to reduce underage drinking. Such efforts may benefit other AI/AN communities seeking to reduce underage drinking.

CR-19-0950: Event-related responses to alcohol-related stimuli in Mexican-American young adults: Relation to age, gender, comorbidity and "dark side" symptoms.

BACKGROUND: Electrophysiological variables may represent sensitive biomarkers of vulnerability to or endophenotypes for alcohol use disorders (AUD). METHODS: Young adults (age 18-30 yrs, n = 580) of Mexican American heritage were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism and event-related oscillations (EROs) generated in response to a task that used pictures of objects, food, and alcohol-related and non-alcohol-related drinks as stimuli. RESULTS: Decreases in energy in the alpha and beta frequencies and higher phase synchrony within cortical brain areas were seen in response to the alcohol-related as compared to the non-alcohol-related stimuli. Differences in ERO energy and synchrony responses to alcohol-related stimuli were also found as a function of age, sex, AUD status and comorbidity. Age-related decreases in energy and increases in synchrony were found. Females had significantly higher energy and lower synchrony values than males. Participants with AUD had higher synchrony values specifically in the beta frequencies, whereas those with a lifetime diagnosis of conduct disorder and/or antisocial personality disorder had lower alpha power and synchrony, and those with any affective disorder had lower ERO energy in the beta frequencies. Those with substance-associated affective "dark-side" symptoms had slower reaction times to the task, lower energy in the beta frequencies, lower local synchrony in the theta frequencies, and higher long-range synchrony in the delta and beta frequencies. CONCLUSIONS: These findings suggest that EROs recorded to alcohol-related stimuli may be biomarkers of comorbid risk factors, symptoms and disorders associated with AUD that also can differentiate those with "dark-side symptoms".

Indexing the 'dark side of addiction': substance-induced affective symptoms and alcohol use disorders.

BACKGROUND AND AIMS: The emergence of negative affective symptoms during the course of alcohol use disorders (AUDs) (e.g. 'dark side' symptoms) has been suggested theoretically; however, the description of their occurrence is limited. This study operationalized two negative affect symptoms and tested the strength of association between these phenotypes and (1) indicators of the clinical course of the severity of AUD, (2) comorbid Axis I psychiatric disorders, suicidal behaviors and trait neuroticism and (3) whether participants reported drinking to relieve the negative affective symptoms. DESIGN: A retrospective cross-sectional study was used to evaluate associations, using logistic regression, between the two negative affective symptoms and clinical measures of AUD severity and progression as well as comorbidity with other psychiatric disorders and conditions, adjusted for demographic characteristics. SETTING: US community-based studies. PARTICIPANTS: A total of 2568 individuals with AUDs obtained from larger population studies that targeted individuals of European American (n = 1663), Mexican American and American Indian (n = 905) ancestry. MEASUREMENTS: Semi-Structured Assessment for the Genetics of Alcoholism was used to ascertain the two 'dark side' phenotypes, clinical diagnoses, the clinical course of AUD and associated symptoms. The two phenotypes were: (1) being anxious or depressed when trying to cut down or stop drinking and (2) experiencing disabling depression for more than 24 hours while drinking. FINDINGS: Both phenotypes were found to be rare in mild and moderate use disorder and highly prevalent in severe AUDs. Having an independent anxiety or affective disorder and elevated scores on trait neuroticism were also associated significantly with the occurrence of both symptoms, as was alcohol 'craving', elevated treatment-seeking, suicidal behaviors and drinking to relieve the symptoms. CONCLUSIONS: Affective symptoms are common in severe alcohol use disorders are associated with a history of independent affective/anxiety disorders, neuroticism and suicidal behaviors; and may promote further heavy drinking.

Prevention of Underage Drinking on California Indian Reservations Using Individual- and Community-Level Approaches.

OBJECTIVES: To evaluate combined individual- and community-level interventions to reduce underage drinking by American Indian/Alaska Native (AI/AN) youths on rural California Indian reservations. METHODS: Individual-level interventions included brief motivational interviewing and psychoeducation for Tribal youths. Community-level interventions included community mobilization and awareness activities, as well as restricting alcohol sales to minors. To test effects, we compared 7 waves of California Healthy Kids Survey data (2002-2015) for 9th- and 11th-grade AI/AN and non-AI/AN students in intervention area schools with California AI/AN students outside the intervention area (n = 617, n = 33 469, and n = 976, respectively). RESULTS: Pre- to postintervention mean past 30-day drinking frequency declined among current drinkers in the intervention group (8.4-6.3 days) relative to comparison groups. Similarly, heavy episodic drinking frequency among current drinkers declined in the intervention group (7.0-4.8 days) versus the comparison groups. CONCLUSIONS: This study documented significant, sustained past 30-day drinking or heavy episodic drinking frequency reductions among AI/AN 9th- and 11th-grade current drinkers in rural California Indian reservation communities exposed to multilevel interventions. Public Health Implications. Multilevel community-partnered interventions can effectively reduce underage alcohol use in this population.

A history of binge drinking during adolescence is associated with poorer sleep quality in young adult Mexican Americans and American Indians.

RATIONALE: Binge drinking during adolescence is common, and adolescents and young adults with alcohol problems may also have sleep difficulties. However, few studies have documented the effects of a history of adolescent binge drinking on sleep in young adulthood in high-risk minority populations. OBJECTIVES: To quantify sleep disturbance, as indexed by the Pittsburgh Sleep Quality Index (PSQI), in a sample of young adult Mexican American and American Indian men and women (18-30 years, n = 800) with and without a history of alcohol binge drinking during adolescence, controlling for age, gender, and race. RESULTS: Gender was found to affect PSQI responses with females reporting waking up at night, having more bad dreams, and later habitual bedtimes than males, and males reporting more problems with breathing and snoring. Increasing age was associated with snoring or coughing, less hours spent in bed, and later evening bedtimes. Race also influenced the PSQI with American Indians reporting longer sleep latencies and sleep durations, more hours spent in bed, and more trouble with coughing and snoring than Mexican Americans, and Mexican Americans reporting later bedtimes. A history of adolescent regular binge drinking was associated with longer sleep latencies, more problems with breathing, bad dreams, and an overall higher PSQI total score, when controlling for age, race, and gender. CONCLUSIONS: This report suggests, like what has been found in young adults in general population samples, that binge drinking during adolescence is associated with deleterious consequences on sleep quality in young adulthood in these high-risk and understudied ethnic groups.

Whole genome sequence study of cannabis dependence in two independent cohorts.

Recent advances in genome wide sequencing techniques and analytical methods allow for more comprehensive examinations of the genome than microarray-based genome-wide association studies (GWAS). The present report provides the first application of whole genome sequencing (WGS) to identify low frequency variants involved in cannabis dependence across two independent cohorts. The present study used low-coverage whole genome sequence data to conduct set-based association and enrichment analyses of low frequency variation in protein-coding regions as well as regulatory regions in relation to cannabis dependence. Two cohorts were studied: a population-based Native American tribal community consisting of 697 participants nested within large multi-generational pedigrees and a family-based sample of 1832 predominantly European ancestry participants largely nested within nuclear families. Participants in both samples were assessed for Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) lifetime cannabis dependence, with 168 and 241 participants receiving a positive diagnosis in each sample, respectively. Sequence kernel association tests identified one protein-coding region, C1orf110 and one regulatory region in the MEF2B gene that achieved significance in a meta-analysis of both samples. A regulatory region within the PCCB gene, a gene previously associated with schizophrenia, exhibited a suggestive association. Finally, a significant enrichment of regions within or near genes with multiple splice variants or involved in cell adhesion or potassium channel activity were associated with cannabis dependence. This initial study demonstrates the potential utility of low pass whole genome sequencing for identifying genetic variants involved in the etiology of cannabis use disorders.

A pilot randomized trial of Motivational Interviewing compared to Psycho-Education for reducing and preventing underage drinking in American Indian adolescents.

Underage drinking is an important public health issue for American Indian and Alaska Native (AI/AN) adolescents, as it is for U. S. teens of all ethnicities. One of the demonstrated risk factors for the development of alcohol use disorders in AI/AN is early age of initiation of drinking. To address this issue a randomized trial to assess the efficacy of Motivational Interviewing (MI) compared to Psycho-Education (PE) to reduce and prevent underage drinking in AI/AN youth was developed and implemented. Sixty-nine youth received MI or PE and 87% were assessed at follow-up. For teens who were already drinking, participating in the intervention (MI or PE) was associated, at follow-up, with lower quantity×frequency (q×f) of drinking (p=0.011), fewer maximum drinks per drinking occasion (p=0.004), and fewer problem behaviors (p=0.009). The MI intervention resulted in male drinkers reporting a lower q×f of drinking (p=0.048) and female drinkers reporting less depression (p=0.011). In teens who had not started drinking prior to the intervention, 17% had initiated drinking at follow-up. As a group they reported increased quantity×frequency of drinking (p=0.008) and maximum drinks (p=0.047), but no change in problem behaviors. These results suggest that intervening against underage drinking using either MI or PE in AI/AN youth can result in reduced drinking, prevention of initiation of drinking, and other positive behavioral outcomes. Brief interventions that enhance motivation to change as well as Psycho-Education may provide a successful approach to reducing the potential morbidity of underage drinking in this high-risk group.