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Neuropsychopharmacology. 2016 Jul;41(8):2001-10. doi: 10.1038/npp.2015.370. Epub 2015 Dec 28.

Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

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Department of Psychiatry, University of Cambridge, Cambridge, UK.
Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
Liaison Psychiatry Service, Norfolk and Suffolk NHS Foundation Trust, Ipswich, UK.
Department of Psychology, University of Cambridge, Cambridge, UK.
Institute of Behavioural and Clinical Neuroscience, University of Cambridge, Cambridge, UK.
Department of Psychology, Centre for Gambling Research at UBC, University of British Columbia, Vancouver, Canada.


Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

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