Dopamine, fronto-striato-thalamic circuits and risk for psychosis.
A series of parallel, integrated circuits link distinct regions of prefrontal cortex with specific nuclei of the striatum and thalamus. Dysfunction of these fronto-striato-thalamic systems is thought to play a major role in the pathogenesis of psychosis. In this review, we examine evidence from human and animal investigations that dysfunction of a specific dorsal fronto-striato-thalamic circuit, linking the dorsolateral prefrontal cortex, dorsal (associative) striatum, and mediodorsal nucleus of the thalamus, is apparent across different stages of psychosis, including prior to the onset of a first episode, suggesting that it represents a candidate risk biomarker. We consider how abnormalities at distinct points in the circuit may give rise to the pattern of findings seen in patient populations, and how these changes relate to disruptions in dopamine, glutamate and GABA signaling.
Brain & Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia. Electronic address: orwa.dandash@monash.edu.
Orwa
O
Dandash
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia; Centre for Neural Engineering (CfNE), Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, VIC, Australia.
Christos
C
Pantelis
Brain & Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, and Monash Biomedical Imaging, Monash University, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.
Alex
A
Fornito
D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D012306:Risk; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism*
D004298:Dopamine
Dopamine; Fronto-striato-thalamic; GABA; Glutamate; Resting-state; fMRI