Original ArticlesP300 decrements in teenagers with conduct problems: implications for substance abuse risk and brain development
Introduction
In recent years, researchers have studied brain electrical activity in an attempt to identify subtle abnormalities in brain function that might precede and perhaps promote the development of chronic alcohol and drug abuse and dependence. Among the electroencephalographic measures used in studies of both substance dependent patients and individuals at risk for substance dependence is the P300 component of the event-related potential. P300 denotes a wave of brain electrical activity emerging approximately 300 milliseconds following the presentation of a rare or surprising stimulus—particularly when the occurrence of the stimulus must be actively acknowledged by the subject, e.g., by pressing a response key. P300, therefore, appears to reflect a cognitive operation associated with revising the mental representation of attended aspects of the recent or current environment. A recent localization study employing both functional magnetic resonance imaging and dipole modeling techniques suggested that the P300 recorded from the scalp originates from neural generators in frontal (anterior cingulate) and parietotemporal (supramarginal gyrus) regions of the brain (Menon et al 1997).
Several studies indicate that abnormalities in the P300 recorded from substance-dependent patients do not disappear, even after long periods of abstinence. In alcohol-dependent patients, for example, P300 amplitude decrements are still detectable after 1 year of abstinence (Porjesz and Begleiter 1985). In cocaine-dependent patients, P300 amplitude decrements, particularly over frontal areas of the brain, are equally persistent (Bauer 1997). It is theorized that P300 fails to normalize in “recovered” patients because of permanent alterations in brain function existing prior to the onset of substance abuse. In fact, studies of the biologic offspring of alcohol-dependent fathers, who are 3 to 4 times more likely to develop alcohol problems than offspring of nonalcoholics, have demonstrated P300 amplitude decrements Begleiter et al 1984, Benegal et al 1995, Elmasian et al 1982, Hill et al 1990, Hill and Steinhauer 1993, O’Connor 1986, Whipple et al 1988 similar to those found in their alcohol- or drug-dependent parent(s) (see Polich et al 1994, for a review). Thus, P300 decrements and substance dependence vulnerability both appear to be transmitted from substance-dependent parents to their offspring. Whether P300 decrements are only a coincident “marker” of vulnerability or make a direct etiologic contribution to risk for substance dependence is still unknown.
Despite the attention afforded to P300 in studies focusing on the familial transmission of risk for substance dependence, it is important to recognize that P300 abnormalities are not specific to a family history of substance dependence. Similar abnormalities have been found among the biologic offspring and/or first-degree relatives of patients afflicted with schizophrenia Blackwood and St Clair 1991, Friedman et al 1982, Friedman and Squires-Wheeler 1994, Kidogami et al 1991, Roxborough et al 1993, bipolar or major affective disorder Friedman et al 1995, Squires-Wheeler and Erlenmeyer-Kimling 1993, or Alzheimer’s disease (Boutros et al 1995). P300 amplitude decrements have also been repeatedly demonstrated among individuals with no family history of substance dependence, but with histories of childhood conduct disorder Bauer et al 1994a, Bauer et al 1994b, O’Connor 1994—a disorder characterized by repeated acts of aggression, destruction of property, deceitfulness or theft, and serious violations of rules prior to age 15. Conduct disorder is strongly associated with an increased risk for substance abuse/dependence. However, unlike a family history of substance dependence, childhood conduct disorder is a risk factor for a wide range of adult psychiatric problems, including dependence (Robins and Price 1991).
One goal of the present study is to determine if the subtle brain dysfunction reflected by reduced P300 amplitude indicates future risk for alcohol and drug dependence by virtue of its association with the child’s family history. Alternately, it is possible that reduced P300 amplitude reflects future risk because it is associated with a factor—namely, a personal history of conduct disorder—that nonspecifically increases risk for a number of adult psychiatric disorders. To disentangle these complex effects, teenaged children were initially categorized on the basis of three types of family history: 1) a family history of alcohol dependence (FHA); 2) a family history of heroin or cocaine dependence (FHD); or 3) a family history of neither alcohol nor drug dependence (FH−). In addition, the teenagers were further classified according to the relative number of conduct disorder problem behaviors (abbreviated CDP− or CDP+) exhibited before 15 years of age. The data analysis was designed to permit tests of the independent and interactive effects of these family history and conduct disorder problem variables.
The second goal of the present study was to discern if there is an optimal age at which the subtle brain dysfunction imparting increased risk can be detected. During childhood and adolescence, the human brain continues to mature and differentiate. The last area of the brain to mature is the frontal region, which regulates higher level cognitive operations, including foresight and impulse control. Because the brain is actively changing and developing new connections during adolescence (Anokhin et al 1996), it is unclear whether the differences in brain function that confer increased risk for alcohol and drug dependence can be detected at an early age, or whether the differences are best detected after the growth process has attained an asymptote. Indeed, clinical studies suggest that many problematic high-risk behaviors exhibited during childhood and early adolescence resolve over time (Storm-Mathisen and Vaglum 1994). However, high-risk behaviors that are present during late adolescence are less likely to resolve and more likely to predict poor adult outcomes. Accordingly, one might hypothesize that the neural correlates of risk for substance dependence will differ over time.
Section snippets
Subjects
The research subjects in the current study were males and females, aged 15 to 20 years. The majority were recruited by a parental response to newspaper advertisements or presentations at alcohol/drug treatment programs and support groups. The remainder were contacted through presentations before high school classes or through guidance counselors, YMCA/YWCA organizations, police athletic leagues, or similar venues. A prospective subject or his/her parent were invited to telephone a research
Demographic and substance use characteristics
Twelve study groups were defined by the factorial combinations of family history (FH−/FHA/FHD), conduct disorder problems (CDP−/CDP+), and gender (male/female) variables. Differences among the groups were evaluated using a 3-way analysis of variance (ANOVA) for continuous variables or Fisher’s exact test for categorical variables. Tukey post hoc tests were used to further examine the source of a significant main effect or interaction.
Analyses of the demographic data (Table 1)revealed that
Discussion
The principal finding of the present study was a reduction in P300 amplitude among teenagers with increased conduct disorder problems. This finding is consistent with the results of other studies demonstrating reduced P300’s among those nondrug-dependent or cocaine-dependent adults who manifest the adult form of childhood conduct disorder, antisocial personality disorder Bauer 1997, Bauer et al 1994a, Bauer et al 1994b. It is also consistent with the results of studies reporting a significant
Acknowledgements
This research was supported by Public Health Service Grants R01-DA08598, R01-DA05826, and P50-AA03510.
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