Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia.
The prevalence of treatment-resistant schizophrenia points to a discrete illness subtype, but to date its pathophysiologic characteristics are undetermined. Information transfer from ventral to dorsal striatum depends on both striato-cortico-striatal and striato-nigro-striatal subcircuits, yet although the functional integrity of the former appears to track improvement of positive symptoms of schizophrenia, the latter have received little experimental attention in relation to the illness. Here, in a sample of individuals with schizophrenia stratified by treatment resistance and matched controls, functional pathways involving four foci along the striatal axis were assessed to test the hypothesis that treatment-resistant and non-refractory patients would exhibit contrasting patterns of resting striatal connectivity. Compared with non-refractory patients, treatment-resistant individuals exhibited reduced connectivity between ventral striatum and substantia nigra. Furthermore, disturbance to corticostriatal connectivity was more pervasive in treatment-resistant individuals. The occurrence of a more distributed pattern of abnormality may contribute to the failure of medication to treat symptoms in these individuals. This work strongly supports the notion of pathophysiologic divergence between individuals with schizophrenia classified by treatment-resistance criteria.
Cognition, Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, London, UK.|School of Psychology, University of Birmingham, Birmingham, UK.
Thomas P
TP
White
Cognition, Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, London, UK.|Beth Israel Deaconess Medical Center, EEG Lab, Neurology, Boston, MA, USA.|Harvard Medical School, Department of Neurology, Boston, MA, USA.
Rebekah
R
Wigton
Cognition, Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Dan W
DW
Joyce
Cognition, Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Tracy
T
Collier
School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, VIC, Australia.
Alex
A
Fornito
Cognition, Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Sukhwinder S
SS
Shergill
D000328:Adult; D001931:Brain Mapping; D003342:Corpus Striatum / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D009434:Neural Pathways / Q000503:physiopathology; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013378:Substantia Nigra / Q000503:physiopathology*