History of alcoholism
thought of as moral weakness or unresolved conflict, now seen as neurological with genetic influence
GxE interaction
need access to substances and genetic influence for addiction
Alcohol abuse
1 DSM IV criteria, alcohol use determined for individuals using quantity and frequency
Alcohol dependence
3 DSM IV criteria
sex differences
men have higher prevalence, health effects are worse in women, women more likely to have comorbid disorders, women more likely to have alcoholic partners - more violence risk
onset of use
early onset = 12-14yrs, late onset= 18-20 yrs
onset of dependence
early onset is less than 18 yrs, late onset is greater than 18 yrs
US prevalence of alcoholism
males= 20%, females= 8%, mean onset of alcoholism = 20yrs
Family risk for alcoholism
2-3X greater for family than general prevalence
Influence on drinking
depends on what age and level of drinking, at 14yrs genes contribute little, shared e= 40%, at 23yrs shared e contributes little, genetics= 40%
initiation
h2=26%, shared e= 65%, shared sib and peer environment more important than parent influence
Early alcohol use
genes not important, CD behavior and shared e are important, heritability may be higher in boys for early drinking
Early use and dependence
if try alcohol before 15yrs, lifetime rate of dependence 4x greater than trying after age 20yrs
Sex difference for early use
55% males, 25% females who drank before age 14 who became alcoholics
Generalized disinhibiton
early age of alcohol use assoc. w/ nicotine dependence and other drug use, ADHD, CD, ASPD
Adult community-based studies
no sex differences- equal h2 for males and females, heritability and e2 were main factors, no c2
Clinical sample from treatment centers
genetic influence less for late onset, environment more important for mael late onset and female early onset, no genetic influence in females, age of first drink correlated with dependence but less for abuse
Alcoholism Type 1
no tendency towards aggression when drinking
Alcoholism Type II
displays alcohol related aggression, more common in males, higher heritability
psychopharmacogenetics
genetic effects on behavioral responses to drugs
Animal Studies
genetic influence indicated on all aspects studied: preference for alcohol, sensitivity to alcohol, susceptibility to withdrawal symptoms, response to alcohol, development of tolerance
*2 allele on ALDH2 Gene for alcoholism
produces aldehyde dehydrogenases which changes alcohol into acetic acid, XX=never alcoholics, Xx= some protective effects (flushing response), if *2 absent, also increased risk 6-10x for esophageal cancer
GABA-A receptor gene for alcoholism
behavioral effects of alcohol, GABRA2 alleles with alcohol dependence
Nicotinic ACH receptors for alcoholism
CHRNA and CHRNB alcohol dependence and smoking frequenty co-occur, evidence for shared genetic vulnerability
dopamine system
reward behavior for drinking from dopamine release
DRD2 and DRD4
alleles of both may have effects on severity of alcoholism
COMT
decrease in COMT activity increases active time for dopamine
CNR1 C allele
assoc. with polysubstance abuse, maybe SZ, carriers report increased level of craving
Why locate specific alleles?
understand etiology of addictions, developing treatments