title: Central nervous system serotonergic responsivity and aggressive disposition in men.
abstract: To determine whether normative variability in aggressive behavior correlates negatively with central nervous system (CNS) serotonergic function among men, plasma prolactin (PRL) responses to a standard fenfluramine challenge (administered to assess central serotonergic responsivity) were examined in relation to interview-assessed aggression histories among 118 adult males derived from a nonpatient, community sample. Fenfluramine-induced, peak PRL rises were smaller in subjects whose 'aggression' scores fell above the sample median, compared to their less aggressive counterparts (P<.002). Across subjects, participants' peak PRL responses likewise covaried inversely with aggression history (r(s)=-.32, P<.0005). Additional analyses were conducted on data of 58 subjects who had also been genotyped for a functional polymorphism in the promoter region of the X chromosomal, monoamine oxidase-A (MAO-A) gene. The four variants of this repeat polymorphism were grouped for analysis (alleles '1+4' vs. '2+3') based on prior report of enhanced transcriptional efficiency in MAO-A promoter constructs containing alleles 2 and 3 (repeats of intermediate length). Men in the 2/3 allele group had significantly higher aggression scores (P<.05) and smaller peak PRL responses to fenfluramine (P<.009) than men in the 1/4 allele group. When adjusted by analysis of covariance for concomitant variability in subjects' PRL responses, aggressive disposition no longer varied significantly by genotype. This finding suggests that association of the MAO-A promoter polymorphism with this behavioral phenotype may be mediated, in part, by allele-specific variation in central serotonergic responsivity.
authors.affiliation: Behavioral Physiology Laboratory, Department of Psychology, University of Pittsburgh, PA, USA. manuck@pitt.edu
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Manuck
authors.forename: Janine D
authors.initials: JD
authors.lastname: Flory
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Muldoon
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology*; D005277:Fenfluramine; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D010556:Personality Tests; D010641:Phenotype; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase / Q000502:physiology
chemical_list: D005277:Fenfluramine; D008995:Monoamine Oxidase; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase