Central nervous system serotonergic responsivity and aggressive disposition in men

Area of Science:

• Neuroscience
• Behavioral Genetics
• Psychopharmacology

Background:

• Aggressive behavior is a complex phenotype influenced by genetic and neurobiological factors.
• Central nervous system (CNS) serotonergic pathways are implicated in the regulation of aggression.
• Variability in aggressive behavior may correlate with differences in serotonergic function.

Purpose of the Study:

• To investigate the relationship between normative variability in aggressive behavior and CNS serotonergic function in men.
• To examine the association between plasma prolactin (PRL) response to fenfluramine and aggression history.
• To explore the role of MAO-A gene polymorphism in mediating this relationship.

Main Methods:

• 118 adult males from a community sample underwent fenfluramine challenge testing to assess central serotonergic responsivity via plasma PRL levels.
• Aggression history was assessed through interviews.
• 58 subjects were genotyped for a functional polymorphism in the MAO-A gene promoter region.

Main Results:

• Smaller peak PRL responses to fenfluramine were observed in men with higher aggression scores.
• Aggression history showed an inverse correlation with peak PRL responses.
• Men with MAO-A alleles '2+3' exhibited higher aggression scores and lower PRL responses compared to those with alleles '1+4'.
• After adjusting for PRL response, the association between MAO-A genotype and aggression was no longer significant.

Conclusions:

• Lower central serotonergic function is associated with higher levels of aggression in men.
• The MAO-A promoter polymorphism's association with aggression may be partly mediated by its influence on central serotonergic responsivity.