Common genetic risk factors for conduct disorder and alcohol dependence.

Abstract

The association between retrospectively reported childhood conduct disorder (CD) and a history of alcohol dependence (AD) was examined in a sample of 2,682 male, female, and unlike-sex adult twin pairs. There was a strong association between CD and AD in both men (tetrachoric r = .34, odds ratio = 2.8) and women (tetrachoric r = .53, odds ratio = 9.9). Genetic factors accounted for most of the association between CD and AD liability in men and women, with the remainder of the association being due to nonshared individual-specific environmental factors. Genetic inftuences common to CD and AD accounted for 17% and 35% of the genetic variation in AD liability in men and women, respectively, and accounted for 11 % and 23% of the total variation in AD liability in men and women, respectively. The results suggest that there are common genetic risk factors for CD and AD or that CD itself is an important genetically influenced risk factor for AD.

Externalizing disorders in the offspring from the San Diego prospective study of alcoholism

“…In the current sample, once CD was observed in these offspring it had the same relationship with alcohol and drug use and problems that might be expected in any population (Slutske et al, 1998;Tarter et al, 2003;Zucker et al, 2000). Our findings expand that knowledge base by demonstrating the link can still be observed in families with higher educated and more affluent parents who do not evidence ASPD themselves.…”

“…All offspring and parents gave informed consent (and for those less than age 18, informed assent with parental consent) to participate in this ongoing protocol (Schuckit and Gold, 1988;Schuckit and Smith, 2000). Age 14 was selected as the minimum because the two externalizing conditions were likely to be apparent by that time and as an age by which almost 25% of the children will have used at least one illicit drug (40% by age 16), and 45% will have used alcohol (65% by age 16) (Johnston et al, 2005;Slutske et al, 1998). In addition, the age range for sons and daughters was also chosen to reflect an early point for which personal interviews were obtained, and the fact that the adolescent version of the standardized interview described below was used at T25 for all offspring through age 25.…”

“…To participate, a person had to have had experience with alcohol but not be alcohol or drug dependent nor have ASPD, not have a father with ASPD, and participants were chosen so that approximately half had an alcohol-dependent father (i.e., they were FH positive), with each of these men matched to an FH negative control on demography and substance use histories. The exclusion of subjects with ASPD reflected the fact that impulsivity (extreme in that condition) is only one of several intermediate phenotypes related to the alcoholism risk, it is noted in only a minority of alcoholics, it enhances the risk for multiple severe conditions (not just AUDs), and it may not relate to additional endophenotypes such as alcohol-metabolizing enzymes or the level of response to alcohol (Schuckit, 2002;Slutske et al, 1998). At intake, the probands were evaluated for several characteristics hypothesized to be related to the later risk for alcoholism, including their experience with alcohol, nicotine and other substances, personality attributes, and their level of response to alcohol (Schuckit, 2002;Schuckit and Gold, 1988).…”

“…Regardless of the definition, several psychiatric diagnoses have been subsumed under the broad umbrella of externalizing conditions in childhood, including conduct disorder (CD), i.e., early onset aggressive behavior likely to lead to later antisocial personality disorders (ASPD) (Hesselbrock and Hesselbrock, 1992;Scourfeld et al, 2004;Slutske et al, 1998;Thapar et al, 2005), and attention deficit hyperactivity disorder (ADHD), i.e., deficits in focusing attention along with signs of hyperactivity (Biederman et al, 1995;Pedersen et al, 2001). Various studies have reported a link between externalizing behaviors and family histories (FHs) of alcohol use disorders (AUDs), illicit substance use disorders (SUDs), some personality conditions such as ASPD, and mood disorders, especially manic depressive disease (Biederman et al, 1992Henin et al, 2005;Hesselbrock and Hesselbrock, 1992;Ohannessian et al, 2004 a, b;Zucker et al, 2000).…”

“…One such endophenotype involves impulsivity and disinhibition as expressed in CD and ASPD (Schuckit and Smith, 2006;Slutske et al, 1998), and another relates to alcoholmetabolizing enzymes (Li, 2000). The potential impact of these factors had been established by the 1970's when the current San Diego Prospective Study began, and the decision was made to focus on additional characteristics that might contribute to the AUD risk.…”