精神分裂症(面向对象编程)
前额叶皮质
神经科学
NMDA受体
心理学
谷氨酸受体
敌手
医学
精神科
内科学
受体
认知
作者
Alan Antičević,Philip R. Corlett,Michael W. Cole,Aleksandar Savić,Mark Gancsos,Yanqing Tang,Grega Repovš,John D. Murray,Naomi Driesen,Peter T. Morgan,Ke Xu,Fei Wang,John H. Krystal
标识
DOI:10.1016/j.biopsych.2014.07.022
摘要
Background Prefrontal cortex (PFC) function contributes to schizophrenia onset and progression. However, little is known about neural mechanisms behind PFC functional alterations along illness stages. Recent pharmacologic studies indicate that glutamate dysfunction may produce increased functional connectivity. However, pharmacologic models of schizophrenia overlook effects of illness progression on PFC function. This study compared N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist effects in healthy volunteers with stages of schizophrenia with respect to PFC functional connectivity. Methods First, we tested ketamine effects on PFC functional connectivity in healthy volunteers in a data-driven way (n = 19). Next, we compared healthy subjects (n = 96) with three clinical groups: individuals at high risk for schizophrenia (n = 21), people early in their course of schizophrenia (EC-SCZ) (n = 28), and patients with chronic illness (n = 20). Across independent analyses, we used data-driven global brain connectivity techniques restricted to PFC to identify functional dysconnectivity. Results Results revealed robust PFC hyperconnectivity in healthy volunteers administered ketamine (Cohen’s d = 1.46), resembling individuals at high risk for schizophrenia and EC-SCZ. Hyperconnectivity was not found in patients with chronic illness relative to EC-SCZ patients. Results provide the first evidence that ketamine effects on PFC functional connectivity resemble early course but not chronic schizophrenia. Conclusions Results suggest an illness phase-specific relevance of NMDAR antagonist administration for prefrontal dysconnectivity associated with schizophrenia. This finding has implications for the neurobiology of illness progression and for the widespread use of NMDAR antagonists in the development of therapeutics for schizophrenia.
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