Quick Take: Association of Hippocampal Glutamate Levels with Adverse Outcomes in Individuals at Clinical High Risk for Psychosis

Neural hyperactivity in the hippocampus has been shown to play a role in psychosis, as it has been thought to lead to an increase in subcortical dopamine via glutamatergic projections to the striatum. This cross-sectional study aimed to investigate the association between hippocampal glutamate levels in individuals at clinical high risk for psychosis, and their subsequent clinical outcomes. Patients at high risk for psychosis met 1 or more of the following criteria: (1) attenuated psychotic symptoms; (2) brief,

limited intermittent psychotic symptoms (a history of 1 or more episodes of frank psychotic symptoms that resolved spontaneously within 1 week in the past year); or (3) a recent decline in function, together with either the presence of schizotypal personality disorder or a family history of psychosis in a first-degree relative. As part of the study, high-risk individuals (n=86) and healthy controls (n=30) underwent 3-T proton magnetic resonance spectroscopy to measure concentrations of glutamate in the left hippocampus. At a median follow-up of 18.5 months, patients were assessed for transition to psychosis using the Comprehensive Assessment of the At-Risk Mental State. Overall functioning was also assessed using the Global Assessment of Function (GAF) scale. Researchers found that high-risk individuals who became psychotic had significantly higher baseline glutamate levels, as compared to high-risk individuals who did not become psychotic (p=0.048). These patients also had higher levels of creatine (p=0.01) and myo-inositol (p=0.002) compared with clinically high-risk individuals who did not become psychotic. Additionally, significantly higher hippocampal glutamate levels in high-risk patients were associated with poor functional outcomes, as determined by a GAF<65 (8.83 vs. 7.76, p=0.02). In a logistic regression, hippocampal glutamate levels were significantly associated with transition and non-transition to psychosis (OR 1.61, 95% CI, 1.00 to 2.59; p=0.05) and overall functioning (OR 1.71, 95% CI 1.10 to 2.66, p=0.02). Investigators therefore concluded that, in patients at high risk for psychosis, higher baseline hippocampal glutamate levels are associated with both transition to psychosis and poor functional outcomes.

Click to read the study in JAMA Psychiatry

Image: PD

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