- A "phenotype" is a way to measure an observable trait or behavior.
- Researchers examine a phenotype in fathers, "maximum number of drinks ever consumed in 24 hours," as it relates to disorders in their children.
- Paternal maximum alcohol consumption is associated with disruptive behavior disorders, early-onset substance use, and early substance-related problems in male and female offspring.
Many studies of alcoholism and the risks for developing alcoholism draw their samples from people who are receiving or seeking treatment for the disease. In contrast, a manuscript in the December issue of Alcoholism: Clinical & Experimental Research examines data drawn from the Minnesota Twin Family Study (MTFS), an epidemiological examination of twins and their parents that is based on the entire population of twins in Minnesota. The authors seek to determine if the drinking history of a father – specifically, the maximum number of drinks he has ever had in 24 hours – can predict disruptive behavioral disorders, early substance-use initiation, and early substance-related disorders in his children.
"A psychiatric diagnosis such as alcohol dependence is useful for classifying people," said Stephen M. Malone, a research associate with the MTFS and first author of the study. "However, it says little about the etiology of the disorder or the processes by which disorders develop. Alternative or intermediate phenotypes related to alcoholism might tell us more about the processes or vulnerabilities underlying the disorder than diagnostic categories can."
"To date," added Ralph E. Tarter, professor of pharmaceutical sciences and psychiatry at the University of Pittsburgh, "research has focused on primarily the clinical consequences – namely, the presence or absence of alcohol use disorders in parents – as predictors of offspring characteristics. This study extends that research by examining one aspect of parental behavior, specifically, the maximum number of drinks ever consumed in a one-day period. Thus, the study is innovative because it focuses on parent behavior and not severity of clinical disorder. In addition, it is to my knowledge the first to use this indicator to study the child’s psychological disposition and substance disorder symptoms." Tarter added that it is helpful to think of the term "phenotype" as a value, in this case, number of drinks.
Subjects for this study were male and female twins that were either 11 (686 males, 664 females) or 17 (514 males, 562 females) years old upon MTFS enrollment. Researchers examined study participants for several psychiatric diagnoses: conduct disorder, oppositional defiant disorder, and attention deficit hyperactivity disorder. They also assessed early initiation of substance use and symptoms of substance abuse or dependence when participants were approximately 14 (the 11-year-old group 3 years after study enrollment) and diagnoses of substance abuse or dependence in the 17-year-old group.
"We found that a single measure of drinking history in fathers, the maximum number of drinks he ever consumed in a 24-hour period, was associated with disruptive behavior disorders, early substance-use initiation, and early substance-related disorders in both his male and female adolescent children," said Malone. "The results were very consistent across our two age groups. The results paralleled those for paternal diagnoses of alcohol dependence which, by itself, may not be too surprising. However, we also found that the associations between the father’s maximum number of drinks consumed and offspring characteristics could not be accounted for by his dependence diagnosis. Nor could they be explained by other characteristics of the father, such as nicotine dependence and illicit drug abuse or dependence."
In other words, said Tarter, "parents who loaded up the most in a one-day period are more likely to have children who manifest behavior ‘undercontrol,’ deviancy and symptoms of substance problems. This finding shifts the focus from clinical consequences of parents to actual behavior of parents as the predictor of their child’s externalizing disorders which, in turn, predispose to alcohol-use disorders."
Study authors suggest that "maximum number of drinks ever consumed in 24 hours" represents an important phenotype which could supplement Diagnostic and Statistical Manual (DSM) of Mental Disorders diagnoses of alcohol dependence.
"This new phenotype could allow clinicians," said Malone, "to characterize people in terms of the severity of their alcohol-related problems. Currently, the DSM diagnostic system classifies people into two groups: those with alcohol dependence, and those without. A quantitative phenotype such as ‘maximum number of drinks’ could help to locate people more precisely along the continuum of risk. It could help to identify people who are ‘false negatives,’ people who don’t meet diagnostic criteria for alcohol dependence but who nevertheless have substantially elevated vulnerability, which they might pass on to their children."
Malone noted that in another study just published by his group, several groups of 17-year-old boys demonstrated a reduced amplitude of a particular brain wave that has been associated with risk for alcoholism: boys with substance-use and behavioral disorders; boys who by the age of 20 had developed a substance-use disorder; boys whose fathers had substance-use or antisocial personality disorders; and boys whose fathers did not meet criteria for alcohol dependence but consumed what was considered an extreme number of drinks. "These results suggested that ‘maximum number of drinks’ is tapping into the same underlying vulnerability that gives rise to alcohol dependence," he said, "and that this can be observed even in the absence of a DSM diagnosis."
Despite the strength of this study’s findings, "it needs to be emphasized that these children are not merely a ‘chip off the old block,’" said Tarter. "The parents who had the worst scores in terms of consumption also were most likely more severe on a variety of other environmental factors that could compromise the child’s development, such as disrupted marriages, absenteeism, etc." He suggested that future research clarify the extent to which ‘maximum drinks’ is a proxy for bad parenting behavior.
This is in fact one of the directions of future studies. Malone said the MTFS plans to compare 11-year-old children considered high risk because one or both parents reported unusually heavy drinking with children considered low risk because neither parent reported drinking excessively at one time to see which high-risk children develop problems and which do not. "This will help to identify environmental, personality or family factors that influence the developmental trajectories of high-risk kids," said Malone, "such that for some, their vulnerability is expressed behaviorally whereas others avoid having significant problems." The MTFS will also examine the relation between this new phenotype and characteristics of behavioral ‘undercontrol’ and lack of restraint in its 17-year-old subjects, as well as what relation may exist between this phenotype among mothers in the sample and problems their children may develop.
Co-authors of the Alcoholism: Clinical & Experimental Research paper included William G. Iacono and Matt McGue of the University of Minnesota. The study was funded by the National Institutes of Health.
University of Minnesota. December 2002.