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Research Letter
December 29, 2021

Hippocampal Glutamate and Positive Symptom Severity in Clinical High Risk for Psychosis

Author Affiliations
  • 1Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia University Medical Center, New York, New York
  • 2New York State Psychiatric Institute, Department of Psychiatry, Columbia University Medical Center, New York
JAMA Psychiatry. 2022;79(2):178-179. doi:10.1001/jamapsychiatry.2021.3710

Clinical high risk (CHR) for psychosis1 is an early phase that offers a unique window of opportunity for studying pathophysiology and subsequently implementing targeted interventions. The hippocampal glutamatergic dysfunction model proposes that N-methyl-D-aspartate receptor hypofunction mediates increased extracellular glutamate specifically in the left hippocampus initially, which then drives hypermetabolism and subsequent atrophy,2,3 heralding the onset of psychotic symptoms. Hippocampal hyperactivity influences downstream dopaminergic circuits resulting in positive symptoms of psychosis.4 Hippocampal atrophy predicts progression to psychosis in CHR with attenuated positive symptom psychosis-risk syndrome (APSS).5

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