Task-evoked substantia nigra hyperactivity associated with prefrontal hypofunction, prefrontonigral disconnectivity and nigrostriatal connectivity predicting psychosis severity in medication naive first episode schizophrenia

SCHIZOPHRENIA RESEARCH

卷:159

Article

Yoon, Jong H.^1,2  Westphal, Andrew J.³  Minzenberg, Michael J.^4,5  Niendam, Tara³  Ragland, J. Daniel³  Lesh, Tyler³  Solomon, Marjorie^3,6  Carter, Cameron S.^3,7 

[1] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[2] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA

[3] Univ Calif Davis, Dept Psychiat, Davis, CA USA

[4] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA

[5] San Francisco VA Med Ctr, San Francisco, CA USA

[6] Univ Calif Davis, MIND Inst, Davis, CA USA

[7] Univ Calif Davis, Ctr Neurosci, Davis, CA USA

关键词: Psychosis;    fMRI;    Substantia nigra;    Prefrontal cortex;    Striatum;    Dopamine;    Basal ganglia;   

DOI  :  10.1016/j.schres.2014.09.022

来源: Elsevier

【 摘 要 】

The widely cited prefrontal dysfunction - excess subcortical dopamine model of schizophrenia posits that prefrontal deficits give rise to cognitive impairments and the disinhibition of subcortical dopamine release underlying psychosis. While this has been one of the most influential schizophrenia models, only a handful of studies have provided evidence supporting it directly in patients with schizophrenia. We previously demonstrated task-evoked substantia nigra hyperactivity in the context of prefrontal hypofunction and prefrontonigral functional disconnectivity. In addition, nigrostriatal functional connectivity was identified as a potential marker of psychosis. Because patients in this prior study had chronic schizophrenia and were treated with antipsychotics, in the present study we tested whether these findings were confounded by illness chronicity and medication effects by seeking to reproduce these findings in an independent sample of antipsychotic naive, first episode (FE) patients. We compared event-related fMRI activations from 12 FE patients with 15 demographically matched healthy control subjects during cognitive testing. We found substantia nigra hyperactivity associated with prefrontal hypofunction and prefrontonigral functional disconnectivity, as well as the magnitude of nigrostriatal functional connectivity positively correlating with severity of psychosis. This study adds to the body of evidence supporting the prefrontal-dopamine model of schizophrenia and further validates nigrostriatal functional connectivity as a marker of psychosis. Published by Elsevier B.V.

【 授权许可】

Free