Serotonin Function and Risk for Alcoholism in Boys with Attention-Deficit Hyperactivity Disorder

Abstract

Data in animals and adults indicate that central serotonergic (5-HT) function may be involved in the development of alcohol abuse. Despite this, studies exploring this mechanism in individuals at risk for alcoholism are scant. This study used a fenfluramine (FEN) challenge procedure to investigate the relationship between risk for alcoholism and 5-HT function in 7-to 11-year-old boys with attention-deficit hyperactivity disorder (ADHD). The prolactin (PRL) and cortisol (CORT) responses to FEN were examined in 10 sons of alcoholic fathers (FA ϩ ) and 30 sons of nonalcoholic fathers (FA Ϫ)A substantial animal and human literature exists in support of an association between central serotonergic (5-HT) function and the development and maintenance of alcohol abuse and dependence. Experimental manipulations in animals that deplete central 5-HT increase alcohol consumption (Ho et al. 1974), whereas interventions that increase 5-HT neurotransmission decrease alcohol intake (Lu et al. 1993). Furthermore, several different rat species genetically bred to prefer alcohol, but kept alcohol-naive, have been found to have decreased 5-HT neurotransmission (Murphy et al. 1982;Zhou et al. 1991).Clinical research in alcohol-dependent individuals has also provided support for the involvement of 5-HT in the development of alcoholism. Alcoholics exhibit abnormalities in a host of parameters of 5-HT function: decreased plasma levels of tryptophan (Branchey et al. 1981); a decreased plasma ratio of tryptophan to other amino acids that compete with it for transport (Branchey et al. 1981); decreased platelet 5-HT content (Bailly et al. 1993); and increased platelet 5-HT uptake (Daoust et al. 1991). Abstinent alcoholics have also been found to exhibit lower cerebrospinal fluid (CSF) levels of the major 5-HT metabolite, 5-hydroxyindole acetic acid (5-HIAA; Ballenger et al. 1979), which normalized after 1 week of drinking (Zarcone et al. 1975 (Naranjo et al. 1984(Naranjo et al. , 1987. In aggregate, the evidence indicates that dysfunction in 5-HT neurotransmission may be associated with a propensity toward alcohol abuse and dependence. However, the results from studies using alcoholics as subjects must be interpreted cautiously, because alcohol has been found to affect 5-HT function (for review, see LeMarquand et al. 1994). Given that genetic factors appear to play a role in the development of alcoholism (Bohman et al, 1987), the study of nonalcoholic individuals who are a high genetic risk for alcoholism may prove a fruitful strategy for investigating the neurochemical propensity to alcohol abuse. Interestingly, nonalcoholic relatives of alcoholics have been found to exhibit increased platelet 5-HT uptake (Ernouf et al. 1993, Rausch et al. 1991, which suggests a decreased availability of 5-HT in the synapse.Longitudinal research indicates that children with attention-deficit hyperactivity disorder (ADHD) are at high risk for developing alcoholism during adolescence (Blouin et al. 1978) and adulthood (Greenfield et al. 1988). Furthermore, f...