Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism.

OBJECTIVE: A deficit in serotonergic neurotransmission has been linked to impulsive behavior, as well as to disorders characterized by disinhibition. The present study tested the hypothesis that young men at high risk for alcoholism demonstrate greater behavioral disinhibition after acute dietary depletion of tryptophan, the amino acid precursor of serotonin. METHOD: A double-blind, placebo-comparison, between-subjects study design was used. Nonalcoholic young men with a multigenerational paternal family history of alcoholism (N = 13) or with no family history of alcoholism (N = 15) in two previous generations were administered mixtures of tryptophan-deficient amino acid to achieve plasma tryptophan depletion. Comparison subjects with a multigenerational paternal family history of alcoholism (N = 1) and comparison subjects with no family history of alcoholism (N = 18) were given a balanced mixture. Five hours after this, all were tested on a modified Taylor task and a go/ no-go task measuring aggressive response and disinhibition, respectively. RESULTS: Plasma tryptophan levels were reduced by 89% in both groups. Tryptophan depletion had no effect on aggressive response. In contrast, tryptophan-depleted individuals with a family history of alcoholism made more commission errors (responses to stimuli associated with punishment or loss of reward) than did tryptophan-depleted individuals with no family history of alcoholism and those receiving the balanced (comparison) mixture of amino acid in either group. CONCLUSIONS: Low serotonin levels may be implicated in the high disinhibition or impulsivity observed in some individuals with a genetic vulnerability to alcohol abuse or dependence.

Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males.

Low serotonin has been associated with aggressive behavior and impulsivity. Executive functions (cognitive abilities involved in the initiation/maintenance of goal attainment) have also been related to aggression. We tested whether dietary depletion of tryptophan, the amino acid precursor of serotonin, would increase disinhibition (impulsivity) in aggressive male adolescents. Cognitive-neuropsychological variables predictive of disinhibition were explored. Stable aggressive and nonaggressive adolescent men received balanced and tryptophan-depleted, amino acid mixtures separately (counterbalanced, double-blind). Commission errors on a go/no-go learning task (i.e., failures to inhibit responding to stimuli associated with punishment/nonreward) measured disinhibition. Aggressive adolescent males made more commission errors as compared to nonaggressives. Lower executive functioning was significantly related to commission errors over and above conventional memory abilities. Tryptophan depletion had no effect on commission errors in the aggressive adolescents, possibly because of a ceiling effect.

Ethanol-induced change in cardiac and endogenous opiate function and risk for alcoholism.

Susceptibility to alcoholism varies with age, gender, and familial background. Youthful nonalcoholic males with multigenerational family histories of male alcoholism seem at particular risk. Previous investigations suggest that such males are characterized by abnormal psychophysiological response, while sober and alcohol-intoxicated; additional recent studies indicate that the endogenous opiate systems are involved in mediating ethanol reinforcement and modulating intake. We first compared cardiac response to alcohol administration among young (mean = 22.8 years), nonalcoholic men and women with multigenerational, unigenerational, and negative family histories of alcohol dependence and abuse. Then, we compared the ethanol-induced cardiac response of the males in these three groups to that of currently alcohol-dependent older males and age-matched nonalcoholic male controls. Finally, we examined ethanol-induced change in plasma beta-endorphin and cortisol levels among a subset of the nonalcoholic males, divided into those with high and low levels of postethanol administration heart-rate increase. Nonalcoholic males with multigenerational family histories of male alcoholism were characterized by significantly higher [t(301) = 5.70, p < 0.0001, Cohen's d = 0.73] levels of ethanol-induced heart-rate increase than nonalcoholics from all other comparison groups. The magnitude of their increase matched that of current male alcohol-dependents. Nonalcoholic males with high levels of ethanol-induced heart-rate increase also produced significantly more plasma beta-endorphin after consuming alcohol. Peak production of beta-endorphin was highly correlated (r = 0.861, p < 0.001) with magnitude of heart-rate increase. A subset of those at risk for alcoholism may be characterized by sensitivity to ethanol-induced reward, marked by heightened ethanol-induced, heart-rate increase, mediated by ethanol stimulation of endogenous opiate production. This subset might contain those who, once alcoholic, would differentially benefit from treatment with opiate antagonists.