Cortical stress regulation is disrupted in schizophrenia but not in clinical high risk for psychosis

Christin Schifani, Huai Hsuan Tseng, Miran Kenk, Abanti Tagore, Michael Kiang, Alan A. Wilson, Sylvain Houle, Pablo M. Rusjan, Romina Mizrahi

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

摘要

While alterations in striatal dopamine in psychosis and stress have been well studied, the role of dopamine in prefrontal cortex is poorly understood. To date, no study has investigated the prefrontocortical dopamine response to stress in the psychosis spectrum, even though the dorsolateral and medial prefrontal cortices are key regions in cognitive and emotional regulation, respectively. The present study uses the high-affinity dopamine D 2/3 receptor radiotracer 11 C-FLB457 and PET together with a validated psychosocial stress challenge to investigate the dorsolateral and medial prefrontocortical dopamine response to stress in schizophrenia and clinical high risk for psychosis. Forty participants completed two 11 C-FLB457 PET scans (14 antipsychotic-free schizophrenia, 14 clinical high risk for psychosis and 12 matched healthy volunteers), one while performing a Sensory Motor Control Task (control) and another while performing the Montreal Imaging Stress Task (stress). Binding potential (BP ND) was estimated using Simplified Reference Tissue Model with cerebellar cortex as reference region. Dopamine release was defined as per cent change in BP ND between control and stress scans ( "BP ND) using a novel correction for injected mass. Salivary cortisol response ( "AUC I) was assessed throughout the tasks and its relationship with dopamine release examined. 11 C-FLB457 binding at control conditions was significantly different between groups in medial [F(2,37) = 7.98, P = 0.0013] and dorsolateral [F(2,37) = 6.97, P = 0.0027] prefrontal cortex with schizophrenia patients having lower BP ND than participants at clinical high risk for psychosis and healthy volunteers, but there was no difference in "BP ND among groups [dorsolateral prefrontal cortex: F(2,37) = 1.07, P = 0.35; medial prefrontal cortex: F(2,37) = 0.54, P = 0.59]. We report a positive relationship between "AUC I and 11 C-FLB457 "BP ND in dorsolateral and medial prefrontal cortex in healthy volunteers (r = 0.72, P = 0.026; r = 0.76, P = 0.014, respectively) and in participants at clinical high risk for psychosis (r = 0.76, P = 0.0075; r = 0.72, P = 0.018, respectively), which was absent in schizophrenia (r = 0.46, P = 1.00; r = 0.19, P = 1.00, respectively). Furthermore, exploratory associations between "BP ND or "AUC I and stress or anxiety measures observed in clinical high risk for psychosis were absent in schizophrenia. These findings provide first direct evidence of a disrupted prefrontocortical dopamine-stress regulation in schizophrenia.

原文English
頁(從 - 到)2213-2224
頁數12
期刊Brain
141
發行號7
DOIs
出版狀態Published - 2018 七月 1

All Science Journal Classification (ASJC) codes

  • 神經病學(臨床)

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