title: Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery.
abstract: Functional imaging methods such as fMRI have been widely used to gain greater understanding of brain circuitry abnormalities in CNS disorders and their underlying neurochemical basis. Findings suggest that: (1) drugs with known clinical efficacy have consistent effects on disease relevant brain circuitry, (2) brain activation changes at baseline or early drug effects on brain activity can predict long-term efficacy; and (3) fMRI together with pharmacological challenges could serve as experimental models of disease phenotypes and be used for screening novel drugs. Together, these observations suggest that drug related modulation of disease relevant brain circuitry may serve as a promising biomarker/method for use in drug discovery to demonstrate target engagement, differential efficacy, dose-response relationships, and prediction of clinically relevant changes.
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK; School of Psychology and Psychiatry, Monash University, Australia; New Medicines, UCB Pharma, Belgium. Electronic address: Pradeep.Nathan@ucb.com.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, USA; Mental Health Service Line, Jesse Brown VA Medical Center, Chicago, USA.
authors.forename: K Luan
authors.initials: KL
authors.lastname: Phan
authors.affiliation: Department of Psychiatry, Oxford University, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, UK.
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.affiliation: Brain Mapping Unit, Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK; GSK Clinical Unit Cambridge, GlaxoSmithKline, UK.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D001523:Mental Disorders / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D015415:Biomarkers