NMDA hypofunction in the posterior cingulate as a model for schizophrenia: An exploratory ketamine administration study in fMRI

Georg Northoff, Andre Richter, Felix Bermpohl, Simone Grimm, Ernst Martin, Valentine Leslie Marcar, Constance Wahl, Daniel Hell, Heinz Boeker

研究成果: 雜誌貢獻文章

61 引文 斯高帕斯(Scopus)


Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate. We investigated 16 healthy subjects which were assigned to either placebo (n=7; saline) or ketamine (n=9; 0.6 mg/kg/h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire. The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine. The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia.
頁(從 - 到)235-248
期刊Schizophrenia Research
出版狀態已發佈 - 一月 1 2005


ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Neurology
  • Psychology(all)