Serotonin, impulsivity, and alcohol use disorders in the older adolescent: a psychobiological study

BACKGROUND: Alcohol use disorders (AUDs) among adolescents are associated with a high prevalence of conduct disorder (CD), much as type II alcoholism in adults is associated with impulsive-aggressive behavior and antisocial personality traits. Adults with impulsive personality disorders and AUD demonstrate diminished central serotonergic responsiveness to serotonergic agonists. Dysregulation of central serotonergic function may contribute to a vulnerability to impulsive-aggressive behavior, CD, and AUD. We studied older adolescents, both male and female, to examine the relationships between sex, dispositional impulsivity, aggressivity, CD, and responsiveness to serotonergic challenge with d,l fenfluramine (FEN) early in the development of AUD. METHODS: Thirty-six adolescents between the ages of 16 and 21 years were assessed for DSM-IV AUD and other Axis I disorders by using the Psychoactive Substance Use Disorders section of the Structured Clinical Interview for DSM III-R, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, and CD interviews. Impulsivity and aggressivity were assessed by the Barratt Impulsiveness Scale, Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Eysenck Impulsiveness Questionnaire, Youth Self Report, and Multidimensional Personality Questionnaires. FEN was administered as 0.8 mg/kg to a maximum of 60 mg, and blood was sampled at fixed intervals for prolactin, cortisol, fenfluramine, and norfenfluramine levels. RESULTS: Eighteen adolescents (12 male, 6 female) with AUD scored significantly higher on all measures of impulsivity and aggressivity compared with 18 healthy controls (12 male, 6 female). There were no significant differences between groups in peak prolactin or cortisol responses (minus baseline), or area-under-the-curve determinations (AUC); however, 9 subjects with AUD and comorbid CD had significantly elevated cortisol AUC levels compared with subjects with AUD and no CD or with normal controls. In the total sample, cortisol AUC was associated positively with measures of aggression. CONCLUSIONS: Adolescents with early-onset AUD are characterized by impulsivity and aggressivity compared with healthy peers but do not demonstrate the diminished prolactin or cortisol responses to FEN characteristic of adult alcoholics with impulsive-aggression.