title: Genetically dependent modulation of serotonergic inactivation in the human prefrontal cortex.
abstract: Previous research suggests that genetic variations regulating serotonergic neurotransmission mediate individual differences in the neural network underlying impulsive and aggressive behaviour. Although with conflicting findings, the monoamine oxidase-A (MAOA) and the serotonin transporter (5HTT) gene polymorphisms have been associated with an increased risk to develop impulsive and aggressive behaviour. Double knock-out mice studies have also demonstrated that MAOA and 5HTT genes strongly interact in the metabolic pathway leading to the serotonergic inactivation; however, their potential interactive effect in human brain remains uninvestigated. We used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to assess the independent and interactive effects of both MAOA and 5HTT polymorphisms on the brain activity elicited by a response inhibition task in healthy volunteers. Multivariate analysis demonstrated an individual effect of both MAOA and 5HTT polymorphisms and a strong allele-allele interaction in the anterior cingulate cortex (ACC), a key region implicated in cognitive control and in the pathophysiology of impulsive and aggressive behaviour. These findings suggest that the MAOAx5HTT allelic interaction exerts a significant modulation on the BOLD response associated with response inhibition and contribute to validate haplotype models as useful tools for a better understanding of the neurobiology underlying complex cognitive functions.
authors.affiliation: Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, 87050, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Passamonti
authors.forename: Antonio
authors.initials: A
authors.lastname: Cerasa
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Gioia
authors.forename: Angela
authors.initials: A
authors.lastname: Magariello
authors.forename: Maria
authors.initials: M
authors.lastname: Muglia
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
authors.forename: Francesco
authors.initials: F
authors.lastname: Fera
mesh_terms: D000328:Adult; D000483:Alleles; D001923:Brain Chemistry / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D005838:Genotype; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000378:metabolism*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004247:DNA; D008995:Monoamine Oxidase; D010100:Oxygen