title: Neuronal correlates and serotonergic modulation of behavioural inhibition and reward in healthy and antisocial individuals.
abstract: Individuals with antisocial personality disorder (ASPD) are impulsive and show impairment in reinforcement processing. There is increasing evidence for a neurobiological basis of psychopathy, which shares some of the characteristics of ASPD, but research on the neuronal correlates of neuropsychological processes in ASPD remains limited. Furthermore, no research has examined the effects of serotonergic manipulation on brain activations in antisocial groups. In this study, 25 male participants with ASPD (mean age 42.1) and 32 male control participants (mean age 30.5; 25 participants providing usable scans) were randomly allocated to receive the 5-HT(2C)-agonist mCPP or placebo. Participants were scanned using functional magnetic resonance imaging (fMRI) during a behavioural inhibition (Go/NoGo) and a reward task. In comparison to healthy controls the ASPD group showed reduced task related activations in the dorsolateral prefrontal cortex (DLPFC) but increased signal in the pre/subgenual anterior cingulate cortex (ACC) in the Go/No-Go task and increased activation in OFC in the reward task. mCPP modulated brain responses in both tasks in the whole group. Interactions between group and drug occured in bilateral OFC, caudate and ventral pallidum during the reward task but no significant interactions were found in the Go/No-Go task. This suggests that ASPD involves altered serotonin modulation of reward, but not motor inhibition pathways. These findings suggest that ASPD involves altered DLPFC, ACC and OFC function. Altered serotonergic modulation of reward pathways seen in the ASPD group raises the possibility that targeting serotonin systems may be therapeutic.
authors.affiliation: Sir Colin Alan Campbell Building, Institute of Mental Health, Section of Forensic Mental Health, University of Nottingham Innovation Park, Triumph Road, Nottingham NG7 2TU, UK. birgit.vollm@nottingham.ac.uk
authors.forename: Birgit
authors.initials: B
authors.lastname: Völlm
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Shane
authors.initials: S
authors.lastname: McKie
authors.forename: Renate
authors.initials: R
authors.lastname: Reniers
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.forename: Ian M
authors.initials: IM
authors.lastname: Anderson
authors.forename: Steve
authors.initials: S
authors.lastname: Williams
authors.forename: Mairead
authors.initials: M
authors.lastname: Dolan
authors.forename: Bill
authors.initials: B
authors.lastname: Deakin
mesh_terms: D000293:Adolescent; D000328:Adult; D000987:Antisocial Personality Disorder / Q000503:physiopathology* / Q000523:psychology; D002421:Caudate Nucleus / Q000187:drug effects / Q000503:physiopathology; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007175:Impulsive Behavior / Q000503:physiopathology; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways; D009484:Neuropsychology; D010879:Piperazines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D012201:Reward; D012701:Serotonin / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D055815:Young Adult
chemical_list: D010879:Piperazines; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine