Family History of Alcohol Dependence and Childhood Risk Factors
It is well known that alcohol dependence runs in families, but do childhood and adolescence psychiatric disorders make individuals with a family history of alcohol dependence more vulnerable to developing a substance use problem themselves?
Few studies have looked at childhood psychiatric disorders and how these relate to having a family history of alcohol dependence. We set out to answer this question by assessing potential traits that might contribute to, or protect individuals from developing a substance use disorder.
Starting in the early 90’s two longitudinal studies were begun in the Behavioral Genetics Research Program, Department of Psychiatry, University of Pittsburgh School of Medicine and UPMC, to look at offspring from high-risk for alcohol dependence families with the hope of identifying biological and psychological markers in youth that could be used to predict substance use and abuse problems later in life.
Family Study of Men with Alcohol Use Disorders and Alcohol Dependence
In this longitudinal study we recruited pairs of alcohol dependent brothers, their family members and children along with control families without alcohol dependence in their family and who responded to requests for volunteers. Participants completed clinical assessments, took part in laboratory assessments, and provided blood for genetic analyses. Children recruited for this study also took part in a Magnetic Resonance Imaging (MRI) study.
Family Study of Women with Alcohol Use Disorders and Alcohol Dependence
In a complementary longitudinal study we recruited pairs of alcohol dependent sisters, their family members and children along with control families who lived in the same census-track. Participants completed clinical assessments, took part in laboratory assessments and provided a blood sample for genetic analyses. Children recruited for this initiative also took part in a Magnetic Resonance Imaging (MRI) study.
The aim of these studies was to better understand why some individuals with a familial susceptibility go on to develop addiction, in spite of a good environment, while many other individuals with susceptibility do not develop an addiction. Those that have this vulnerability need to realize, however, that susceptibility is not inevitability.
Pathways to Alcohol Dependence
Externalizing Pathways to Alcohol Dependence
Externalizing disorders of childhood and adolescence are a well-known and an often emphasized pathway to alcohol dependence. Externalizing disorders include: Conduct Disorder, Attention Deficit Hyperactivity Disorder, and Oppositional Defiant Disorder.
Among the most publicly known cases of alcohol dependence that grew out of early externalizing symptoms was Terry McGovern, daughter of the late Senator George McGovern.
She was described as frequently running away from home, involved in early smoking, alcohol and drug use and sexual activity.
Internalizing Pathways to Alcohol Dependence
Internalizing disorders of childhood and adolescence are an equally important early sign on the pathway to alcohol dependence but are often less emphasized. Internalizing disorders include: Major Depressive Disorder, Mania, Generalized Anxiety Disorder, Panic Disorder, Phobias, and Obsessive Compulsive Disorder.
Among the most publicly known cases of alcohol dependence that appeared to be driven by internalizing symptoms was that of the late Harold Hughes, former Governor of Iowa, and Senator from Iowa.
In spite of having succumbed to alcohol use disorder (AUD), Senator Hughes got on the path to recovery and made an important contribution to society to help prevent others from developing AUD.
Senator Hughes was instrumental in passing legislation establishing the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in 1970 (Hughes Act).
The Man from Ida Grove
Hughes describes his first drink at a high school dance saying:
“A mellow glow filled me strangely, I was no longer bothered by inhibitions. I spotted the girl I had been watching all evening and walked up to her. It was easy to ask her to dance, even easier to slip my arm around her waist and glide off onto the floor.” Clearly, Senator Hughes’ early initiation to the use of alcohol, and subsequent problems with alcohol was promoted by the relief of anxiety associated with social interactions. He was able to overcome his use of alcohol and having achieved sobriety put his experience to good use by passing legislation that started NIAAA, the major source of funding for alcohol-related studies.
The Man from Ida Grove. Publisher: Chosen Books/Word Books; 1st edition (January 1, 1979)
Results from Our Family Studies
Externalizing Disorders and a Increased Risk for Alcohol and Drug Use Disorders
Children from families with multiple cases of alcohol dependence (High-Risk) and those from families without this background (Low-Risk) were followed through childhood and adolescence into young adulthood. Survival curves for alcohol abuse/dependence and drug abuse/dependence for individuals are displayed below. Note the earlier onset for developing a disorder among the offspring from families with multiple cases of alcohol dependence in comparison to those from lower risk families.
Patterns of Cannabis Use and Family History of Alcohol Dependence
Offspring from high-risk families show varying patterns of cannabis use. Some experiment with cannabis but show declining use as they mature into young adulthood. Others appear to not use cannabis, while others show continued elevated use.
Individuals in the frequent use group were more often from high-risk families with multiple cases of alcohol dependence in their family background (80.0%) and were more often male (68.6%). Among those in the group showing a decline in use during young adulthood, 60.0% were from a familial high-risk background, many of whom started using cannabis in adolescence.
Cannabis Use and Effects on Brain Regions
Neuroimaging of individuals from both the high and low-risk families who differed in their use of cannabis revealed differing volumes of brain regions. The highlighted areas show regions where there are difference in volume in the two groups varying in their use of cannabis. One group used virtually no cannabis up to the time of the neuroimaging. The “No Use” group was disproportionately represented by individuals from the low-risk familial background (58.8%).
The whole brain analysis of the regular users of cannabis, compared to the non-users of cannabis revealed that non-users had larger volumes than regular users in four regions. These include the Lingual Gyrus, Anterior Cingulum (Left and Right), and the Rolandic Operculum (Right). Our results suggest that use of cannabis can have potentially deleterious effects on brain structure. Our next question was “Are all individuals equally affected by use of cannabis”? Might there be differences due to genetic differences.
Reduced volume seen in the Right Anterior Cingulum is an interaction between allelic variation in the CNR1 gene and the cumulative lifetime use of cannabis. Individuals in the “cannabis use above the median” with the “any TA” variation showed a 17.6% reduction in Right Anterior Cingulum volume.
The significance of our Anterior Cingulum findings from a behavioral perspective lies in the potential for long-term use of cannabis to have deleterious effects on motivation. Although there has been some debate over the function of the Anterior Cingulate Cortex (ACC), whether it is a structure dedicated to motivating behavior or designed for cognitive control and reinforcement learning, it is clear that it is involved in goal directed behavior. Reduction of volume of this structure may have long term consequences for motivation.
Internalizing Disorders and a Increased Risk for Alcohol and Drug Use Disorders
Individuals who have either a diagnosis of Major Depressive Disorder or Anxiety Disorder in childhood are at a greater risk of developing a substance use disorder or developing drug abuse/dependence later in life. It is not uncommon for individuals to have both internalizing and externalizing disorders. We find that individuals who have both an internalizing and externalizing disorder develop substance use disorder earlier than individuals with only an internalizing disorder.
Risks Associated with a Family History of Alcohol Dependence
In one of our studiesa we set out to investigate the risks for psychological problems that children and adolescents from families with multiple cases of alcohol dependence experience. In the study we find that:
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Children and adolescents from families with many alcohol dependent relatives had a significantly earlier age of onset to begin drinking and if they developed a substance use disorder it was at an earlier age than those without a family history.
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Adolescents aged 12–18 from families with alcohol dependence were 3.6 times more likely to experience a psychological problem that met diagnostic criteria suggesting a psychiatric disorder during adolescence.
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The children and adolescents with a family history of alcohol dependence showed an increased risk for developing an externalizing disorder. These include problems with attention sometimes meeting criteria for having attention deficit hyperactivity disorder (ADHD) and Conduct Disorder among others.
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Children and adolescents have an increased risk for developing an internalizing disorder.
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Adolescents from families with alcohol dependence had a greater than 4 fold increase in the likelihood of having a depressive disorder than did the adolescents without a family history of alcohol dependence.
a Hill SY, Shen S, Lowers L, Locke-Wellman J, Matthews AG, McDermott M. Psychopathology in offspring from multiplex alcohol dependence families: A prospective study during childhood and adolescence. Psychiatry Res 160:155-166, 2008 PMID:18597856. Read Article
Future Follow Up
We would like to continue following these individuals into the later portions of young adulthood and into middle age to determine if those who develop problems with substances are able to reach sobriety and, if so, what were the factors that were associated with positive outcomes. Additionally, we plan to follow the older generation of individuals who are the grandparents of our child/adolescent follow up cohort. These individuals provide an ideal sample for longitudinal follow up to determine the factors associated with physical health and absence of common disorders such as neurodegenerative disorders.