title: Effects of aripiprazole and haloperidol on neural activation during a simple motor task in healthy individuals: A functional MRI study.
abstract: The dopaminergic system plays a key role in motor function and motor abnormalities have been shown to be a specific feature of psychosis. Due to their dopaminergic action, antipsychotic drugs may be expected to modulate motor function, but the precise effects of these drugs on motor function remain unclear. We carried out a within-subject, double-blind, randomized study of the effects of aripiprazole, haloperidol and placebo on motor function in 20 healthy men. For each condition, motor performance on an auditory-paced task was investigated. We entered maps of neural activation into a random effects general linear regression model to investigate motor function main effects. Whole-brain imaging revealed a significant treatment effect in a distributed network encompassing posterior orbitofrontal/anterior insula cortices, and the inferior temporal and postcentral gyri. Post-hoc comparison of treatments showed neural activation after aripiprazole did not differ significantly from placebo in either voxel-wise or region of interest analyses, with the results above driven primarily by haloperidol. We also observed a simple main effect of haloperidol compared with placebo, with increased task-related recruitment of posterior cingulate and precentral gyri. Furthermore, region of interest analyses revealed greater activation following haloperidol compared with placebo in the precentral and post-central gyri, and the putamen. These diverse modifications in cortical motor activation may relate to the different pharmacological profiles of haloperidol and aripiprazole, although the specific mechanisms underlying these differences remain unclear. Evaluating healthy individuals can allow investigation of the effects of different antipsychotics on cortical activation, independently of either disease-related pathology or previous treatment. Hum Brain Mapp 38:1833-1845, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Rhianna
authors.identifier: 0000-0002-7923-5480
authors.initials: R
authors.lastname: Goozee
authors.affiliation: Centre for Neuroimaging Sciences (CNS), King's College London, London, United Kingdom.
authors.forename: Owen
authors.initials: O
authors.lastname: O'Daly
authors.affiliation: Bristol-Myers Squibb, New York, New York.
authors.forename: Rowena
authors.initials: R
authors.lastname: Handley
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Tiago
authors.initials: T
authors.lastname: Reis Marques
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: Taylor
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Grant
authors.initials: G
authors.lastname: McQueen
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hubbard
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, United Kingdom.|NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London, London, United Kingdom.
authors.forename: Carmine
authors.initials: C
authors.lastname: Pariante
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, United Kingdom.|NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London, London, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Antje A T S
authors.initials: AA
authors.lastname: Reinders
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.|NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London, London, United Kingdom.
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000068180:Aripiprazole; D006220:Haloperidol; D010100:Oxygen
keywords: antipsychotic; functional neuroimaging; motor; schizophrenia