National Institute on Alcohol Abuse and Alcoholism Children of Alcoholics Presentation September 9, 2011

National Institute on Alcohol Abuse and Alcoholism Children of Alcoholics: A Population at Increased Risk A substantial body of research has shown that children of alcoholics are at increased risk of behavioral, social, legal and medical problems. These problems include anxiety disorders, conduct disorder, delinquent behavior, impaired physical health and early initiation of alcohol use and other drugs. Genetics (e.g. having a biological parent with problem drinking) and environment (e.g. childhood exposure to someone with problem drinking) strongly influence one’s risk for developing alcohol use disorders. This puts children of alcoholics at elevated risk for developing alcohol use disorders during adolescence and into adulthood as well as other behavioral and physical disorders.

National Institute on Alcohol Abuse and Alcoholism Children of Alcoholics: A Population at Increased Risk Results of NIAAA’s National Longitudinal Alcohol Epidemiology Survey have shown that as many as 1 in 4 children younger than age 18 in the U.S. is exposed to family alcohol abuse or dependence. Growing up in a household where alcohol is a problem threatens the well-being of children and affects them well into adulthood. The extent of this public health problem reinforces the need to better understand the specific factors that make children of alcoholics so vulnerable, and to develop effective strategies to prevent and intervene with alcohol use disorders on the family level.

National Institute on Alcohol Abuse and Alcoholism The NIAAA Investment in Research on Issues Specific to Children of Alcoholics NIAAA’s Research Portfolio includes Studies that seek to: ­ Identify the specific biological and environmental risk factors that predispose individuals with family histories of alcoholism to develop alcohol use disorders themselves; ­ Understand how these risk factors impact brain structure and function, especially during adolescence; ­ Evaluate the impact on behavioral, emotional and social development; ­ Investigate how these risk factors may predict the developmental course of alcohol problems throughout life.

National Institute on Alcohol Abuse and Alcoholism Specific research examples in these areas include studies to: ­ examine families with strong histories of alcoholism to identify genes that confer increased risk for alcohol use problems, as compared to individuals without strong family histories. ­ assess how brain structure and function, including the developing adolescent brain, differ in high risk and low risk individuals, and how these differences impact emotional and behavioral regulation and the likelihood for developing a substance use disorder, or other behavioral problem, later in life. ­ And to use this knowledge to help individuals become resilient rather than at-risk for suffering from, and perpetuating alcohol and other behavioral problems.

National Institute on Alcohol Abuse and Alcoholism Specific research examples in these areas include studies to: ­ investigate tolerance to alcohol as a risk factor in adolescents and young adults, and how this tolerance may influence a child’s expectations about the effects of alcohol which may lead him or her to use it inappropriately, e.g., to cope with stress. ­ learn how memory, reward, processing of social and spatial information during early adolescence (shown to be impaired in alcohol dependent individuals) serve as risk factors for later adolescent and early adult alcohol use, alcohol problems, and alcohol use disorders.

National Institute on Alcohol Abuse and Alcoholism More Detail on A Few Projects A project led by Robert Zucker entitled Family Study of Risk for Alcoholism Over the Life Course is identifying: ­ very early behavioral and environmental risk factors ; ­ factors that predict recovery and relapse in adulthood.

National Institute on Alcohol Abuse and Alcoholism Results from Zucker’s Michigan Longitudinal Study One of the most consistent predictors of AUD outcome in adulthood is the presence of early (age 3-5) under- controlled behavior. This shows up in various forms, including impulsivity, aggressiveness, rule breaking. There is stability to this effect, suggesting a strong genetic involvement. That is, very early under-control predicts more under- control in adolescence. And in turn, high under-control in predicts a diagnosis of alcohol dependence in early adulthood.

National Institute on Alcohol Abuse and Alcoholism Results from Zucker’s Michigan Longitudinal Study Risks for later problems (such as, early onset of use, more problems in adolescence) tend to derive from multiple co- occurring family factors. First, alcoholic men are more likely to marry alcoholic women (marital assortment). Such families are more likely to have children higher in under- control. Families where fathers are not only alcoholic but also antisocial (i.e. comorbid for antisocial personality disorder) show further correlated risks, i.e., they are even more likely to be married to alcoholic women: ­ there is more family discord/conflict, ­ there are more family crises, ­ there is more likely to be child abuse, and there is more likely to be high child under-control predicted by these factors.

National Institute on Alcohol Abuse and Alcoholism But…… Although it is compelling to attribute all of these elevated risks to genetic influence, which in turn leads to migration into correlated environments, there are also independent effects of context (environment), that are synergistic with those predicted from baseline characteristics. When these other factors are controlled for parent characteristics, these other factors have an independent contribution to long term risk.

National Institute on Alcohol Abuse and Alcoholism Also from the MLS and Similar Studies Early (preschool) predictors between resilient COAs (COAs who do not move into problem drinking in late adolescence) and non- resilient COAs (COAs who evolve into problem drinkers in late adolescence ) include: Resilient- COAs have families with lower levels of conflict, less anti- sociality in the fathers. While early-on the level of internalizing and externalizing problems in all COAs are similar -- over time, non-resilient COAs develop more externalizing and internalizing symptoms than resilient COAs, including: ­ more drinking problems, cigarettes use, ­ illicit drug use ­ they are more likely to have homes that tolerate adolescent drinking (drinking when parents present). ­ Their friends are less involved in school activities and academics, as well as in church, they use alcohol and other drugs more often, they have more sexual involvement and delinquent activity.

National Institute on Alcohol Abuse and Alcoholism And more from MLS… There is very early awareness of alcohol and early development of alcohol expectancies. COAs recognize alcohol earlier, and more of them than non COAs know alcohol product names, can identify alcohol from the smell, know many of the social rules such as that men drink more than women) Non resilient COAs show these traits even earlier than resilient COAs These expectancies independently predict early drinking in adolescence. Moreover, this relationship is present even when controlling for family history. Also, greater risk is shown by earlier and greater positive expectancies about alcohol use.

National Institute on Alcohol Abuse and Alcoholism Zucker’s fMRI Results In response to an affect arousal task, resilient COAs in later adolescence show more activation of the orbital frontal gyrus, bilaterally, and left insula ⁄ putamen than do FH- and nonResilient COAs. Non-resilient COAs in contrast show more activation of the dorsomedial prefrontal cortex and less activation of the ventral striatum and extended amygdala in response to emotional arousal compared to nonCOAs and Resilient COAs. Non-resilient COAs also have more externalizing behavior –consistent with the fact that they are higher in behavioral risk, and this behavior in turn is correlated with increased dorsomedial prefrontal activation and decreased ventral striatal and extended amygdala activation. The responding pattern shown by the resilient COAs indicates an active emotional monitoring function. Thereby, monitoring one’s feelings appears to be protective against indiscriminate or potentially troublemaking behavior. In contrast, nonResilient COAs show a response pattern suggesting active suppression of affective responses. Without appropriate processing of affect a much greater potential exists for deficits in adaptive response to emotionally arousing situations.

National Institute on Alcohol Abuse and Alcoholism Shirley Hill’s Study A project by Shirley Hill entitled Longitudinal Predictors of Alcohol Dependence in Offspring from Multiplex Families is identifying neurobiological determinants and consequences in high risk children; and Determining how brain morphology and function in HR offspring impacts their tendency for emotional dysregulation and behavioral disinhibition and the likelihood that they will develop a substance use disorder (SUD).

National Institute on Alcohol Abuse and Alcoholism William Lovallo and Marc Schuckit A project by William Lovallo called the Oklahoma Family Health Patterns: A Study Across Generations – is examining brain function as a predictor of risk within high density families. Marc Schuckit’s Prospective Study: “Alcoholic & Control Family Offspring” – is further exploring Low Response to Alcohol as a risk factor for alcoholism in FH positive year olds. It appears quite likely that Low Response to alcohol might alter a person's expectations of the effects of alcohol which then enhances the probability of using alcohol to cope with stress. Being FH+ is projected to be associated with a child's observing heavy drinking in the home, which also affects the selection of heavy-drinking friends and problematic coping mechanisms.

National Institute on Alcohol Abuse and Alcoholism A study by Laurie Chassin: Substance Use Among Children of Alcoholics Investigates: ­ the developmental course of alcoholism and trajectories of substance use and SUDs from adolescence to adulthood, including adult "maturing out"; ­ etiological pathways by which risk is transmitted across multiple generations; ­ consequences of substance use; ­ emerging risk in the 3rd generation from a Longitudinal study of COAs to examine familial alcoholism effects on the course of substance use and substance use disorders in the adults -- and on substance use initiation in their children; ­ and the interrelation between the generations: grandparents, their children and grandchildren on drinking behavior.

National Institute on Alcohol Abuse and Alcoholism Another study by Robert Zucker: “Neurocognitive Risk For Alcoholism Into Adulthood” is characterizing the manner in which early and mid adolescent neuropsychological functioning of certain physiological attributes in CoAs and others serve as risk factors for later adolescent and early adult alcohol use, alcohol problems, and alcohol use disorders as well as other substance use disorders. These neurophysiological traits include: (a) executive functioning, especially response suppression and working memory, (b) reward response, including anticipation of reward and response to reward, and (c) secondarily, right hemisphere function, with discrimination between spatial and social information processing ­ The participants in this prospective study of initially high risk children are now moving into late adolescence and early adulthood, the developmental period where the heaviest levels of alcohol and other drug use are likely to occur.

National Institute on Alcohol Abuse and Alcoholism More Studies ­ A study by O’Leary entitled “Brain Development in Adolescents with Genetic Risk Factors for Alcoholism” is assessing the effects of genetic vulnerability to alcoholism on the developing adolescent brain, using cognitive assessments and functional and structural brain imaging; ­ It is further determining whether adolescents at high risk with a range of conduct disorder symptoms differ from normal adolescents regarding brain structure and function? ­ Another study by Shirley Hill entitled: Biological Risk Factors in Relatives of Alcoholic Women” is defining neurobiological determinants of increased risk; how brain morphology and functioning in High Risk offspring impacts their tendency for emotional dysregulation, behavioral disinhibition, and greater SUD & how prenatal exposure may affect those brain areas.

National Institute on Alcohol Abuse and Alcoholism A study by Cathy Bucholz entitled: “Alcoholism: Epidemiologic High Risk Family Study – MOFAM ” ­ This study aims to characterize at baseline and over time in high risk and low risk families: alcohol use problems, abuse and dependence (and the same for tobacco and other drugs) determine the impacts of paternal AD, antisociality and depression, parenting style, parent-offspring relationships and rearing environment on the development and course of alcohol, tobacco and other drug use problems and dependence in offspring from families indexed by different levels of risk based on father's status, and to test for interactions with ethnicity; also tests sibling influences.

National Institute on Alcohol Abuse and Alcoholism COGA And finally, the Collaborative Studies on the Genetics of Alcoholism/COGA (Laura Beirut) -- is following a high risk adolescent population from densely affected families to determine genetic and environmental risk factors, and protective factors, for alcoholism.