Serotonergic dysfunction, negative mood states, and response to alcohol

Background: Dysfunction of central serotonergic neurotransmission has been implicated in the pathogenesis and maintenance of alcoholism. Serotonergic dysfunction may be associated with three behavior patterns relevant for alcoholism: impulsive aggression, negative mood states, and a low response to alcohol intake. Methods: We reviewed the literature on the psychopathological correlates of serotonergic dysfunction and focused on studies that assess the interaction between negative mood states and alcohol response. Results: Prospective studies in nonhuman primates that underwent early separation stress found an association between a low serotonin turnover rate and the disposition to excessive alcohol intake and impulsive aggression. These findings seem to be relevant for a subgroup of alcoholics with a low serotonin turnover rate and antisocial personality traits. Cross-sectional data in humans also support a relationship between reduced serotonergic neurotransmission and aggressive behavior and indicate that the association of serotonergic dysfunction and aggression may be mediated by negative mood states. This hypothesis is in accordance with a large body of data linking anxiety and depression to serotonergic dysfunction. In human alcoholics, brain imaging has detected a reduction in serotonin transporter availability in association with depression. Serotonin transporter availability seems to be related to reduced GABA-ergic sedation and the acute response to alcohol intake, an important predictor of subsequent development of alcohol dependence. Conclusions: Several lines of evidence point to a relationship between serotonergic dysfunction, negative mood states, and excessive alcohol intake, which may be mediated in part by reduced alcohol-induced sedation.