RISK FACTORS OF RISK FACTORS OF ALCOHOL USE DISORDER ALCOHOL USE DISORDER The ABAMF National Center for Addiction Training Fellowship Retreat March 18, 2014 Rachel A. Rizzo, MS, MPH, CHES

Risk Factors  Genetics  Family History  Prenatal Exposure  Early Onset Drinking  Alcohol Tolerance  ADHD  Mood and Anxiety Disorders  History of Abuse

Risk Factor: Genetics – OPRM1  Design: Race-specific meta-analyses of 12 cross- sectional studies  Opioid receptor mu 1 gene (OPRM1) A118G polymorphism and alcohol dependence  Sample: N = 4,282 Caucasians and Asians  Results:  A118G polymorphism positively associated with alcohol dependence among Asians only Chen D, Liu L, Xiao, Peng Y, Yang C, Wang Z. Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asians and Caucasians. Drug Alcohol Depend (1-3):1-6.

Risk Factor: Genetics – DRD2  Design: Meta-analysis of 44 cross-sectional studies  Dopamine receptor D2 gene (DRD2) Taq1A polymorphism and alcohol dependence  Sample: N = 9,382 adults  Results:  OR = 1.38 (95% CI = ) Smith L, Watson M, Gates S, Ball D, Foxcroft D. Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene-disease association review. Am J Epidemiol (2):

Risk Factor: Genetics – 5-HTTLPR  Design: Meta-analysis of 17 case-control studies  Variants in the neurotransmitter serotonin gene (5- HTTLPR) and alcohol dependence  Sample: N = 5,814 adults  Results:  OR = 1.18 (95% CI = ) Feinn R, Nellissery M, Kranzler HR. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. B Neuropsychiatr Genet B(1)79-84.

Protective Factor: ADH1B Variant  Design: Meta-analysis  3 case-control studies (1989, 2000, 2001) examining ADH1B allele and alcohol dependence  Sample: N = 5,510 AA and EA adults  Results: OR = 0.34 (95% CI = 0.24 – 0.48) Bierut LJ, Goate AM, Breslau N, Johnson EO, Bertelsen S, et al. ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. Mol Psychiatry (4):

Protective Factor: ALDH2 Variant  Design: Meta-analysis  53 case-control studies examining ALDH2 allele and alcohol dependence  Sample: N = 17,009 East Asian adults  Results: OR = 0.23 (95% CI = 0.20 – 0.28) Lin D, Zhao H, Gelernter J. Strong protective effect of the aldehyde dehydrogenase gene 504ls (*2) allele against alcoholism and alcohol-induced medical diseases in Asians. Hum Genet (5):

Risk Factor: Family History Elliott JC, Carey KB, Bonafide KE. Does family history of alcohol problems influence college and university drinking or substance abuse? A meta-analytical review. Addiction (10):  Design: Meta-analysis of 53 cross-sectional studies  Family history of alcohol problems and alcohol problems among college students  Sample: N = 89,766 students  Results:  Family history has a moderate effect on alcohol dependence symptoms Cohen’s d = 0.24

Risk Factor: Prenatal Exposure  Design: Prospective cohort (14-year follow up)  Maternal alcohol use during pregnancy and risk of adolescent alcohol use among exposed offspring  Sample: N = 439 mother-offspring pairs  Results:  Prenatal ethanol exposure is predictive of adolescent alcohol use Baer JS, Barr HM, Bookstein FL, Streissguth AP. Prenatal alcohol exposure and family history of alcoholism in the etiology of adolescent alcohol problems. J Stud Alcohol (5):

Risk Factor: Prenatal Exposure  Design: Prospective cohort (21-year follow up)  Continuation of previous study  Maternal alcohol use during pregnancy and risk of adult alcohol-related problems and dependence among exposed offspring  Sample: N = 433 mother-offspring pairs  Results:  Prenatal ethanol exposure is predictive of adult alcohol-related problems and dependence Baer JS, Sampson PD, Barr HM, Connor PD, Streissguth AP. A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking. Arch Gen Psychiatry Stud Alcohol (4):

Risk Factor: Early Onset Drinking  Design: Cross-sectional survey (1992)  National Longitudinal Alcohol Epidemiologic Survey (NLAES)  Age at first use and prevalence of lifetime alcohol dependence  Sample: N = 27, 616 current and former drinkers  Results:  First Use at <14 years, prevalence of AD = 47%  First Use at 21 years, prevalence of AD = 10% Grant BF, Dawson DA. Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: National Longitundinal Alcohol Epidemiologic Survey. J Subst Abuse :

Risk Factor: Early Onset Drinking  Design: Cross-sectional survey ( )  National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)  Age at first use and prevalence of lifetime alcohol dependence  Sample: N = 43,093 adults  Results:  First Use at <14 years, prevalence of AD = 47%  First Use at ≥21 years, prevalence of AD = 9% Hingson RW, Heeren T, Winter MR. Age at drinking onset and alcohol dependence: age at onset, duration, and severity. Arch Pediatr Adolesc Med (7):

Risk Factor: Alcohol Tolerance Schuckit MA. Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry (2):  Design: Longitudinal study (10-year follow up)  Alcohol tolerance at 20 years and prevalence of alcohol dependence at 30 years  Sample: 227 sons of alcohol-dependent parents  Results:  High tolerance ( sensitivity), prevalence of AD = 46%  Low tolerance ( sensitivity), prevalence of AD = 14%

Risk Factor: ADHD  Design: Meta-analysis of 10 longitudinal studies  Childhood attention-deficit/hyperactivity disorder (ADHD) diagnosis and risk of alcohol use disorder in young adulthood (aged years)  Sample: N = 3,184  Results:  Pooled OR = 1.35 (95% CI = ) Charach A, Yeung E, Climans T, Lillie E. Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. J Am Acad Child Adolesc Psychiatry (1):9-21.

Risk Factor: Mood & Anxiety Disorders  Design: Co-twin control study  Mood and anxiety disorders and alcohol use disorder  Sample: N = 208 adult male monozygotic twin pairs  Results: Twins diagnosed with major depressive disorder, dysthymia, and generalized anxiety disorder were more likely to report symptoms of AUD 10 years later than their unaffected co-twin (p<0.05). Blonigen DM, Burroughs T, Haber JR, Jacob T. Psychiatric morbidity is linked to problem drinking in midlife among alcohol-dependent men: a co-twin control study. J Stud Alcohol Drugs (1):

Risk Factor: History of Abuse  Design: Cross-sectional survey  History of abuse and risk of alcohol use disorder  Sample: N = 936 Mexican adolescents aged years (46% female)  Results:  Psychological abuse by mother OR = 2.27* (95% CI = )  Physical abuse by father OR = 1.41 (95% CI = )  Sexual abuse by family member OR = 5.48* (95% CI = ) *statistically significant Caballero MA, Ramos L, Gonzalez C, Saltijeral MT. Family violence and risk of substance use among Mexican adolescents. Child Abuse Negl (8):

Summary  Genetics  Family History  Prenatal Exposure  Early Onset Drinking  Alcohol Tolerance  ADHD  Mood and Anxiety Disorders  History of Abuse

RISK FACTORS OF RISK FACTORS OF ALCOHOL USE DISORDER ALCOHOL USE DISORDER The ABAMF National Center for Addiction Training Fellowship Retreat March 18, 2014 Rachel A. Rizzo, MS, MPH, CHES