Hippocampal glutamate metabolites and glial activation in clinical high risk and first episode psychosis

Abstract

Alterations in glutamate neurotransmission have been implicated in the pathophysiology of schizophrenia, as well as in symptom severity and cognitive deficits. The hippocampus, in particular, is a site of key functional and structural abnormalities in schizophrenia. Yet few studies have investigated hippocampal glutamate in antipsychotic-naïve first episode psychosis patients or in individuals at clinical high risk (CHR) of developing psychosis. Using proton magnetic resonance spectroscopy (1H-MRS), we investigated glutamate metabolite levels in the left hippocampus of 25 CHR (19 antipsychotic-naïve), 16 patients with first-episode psychosis (13 antipsychotic-naïve) and 31 healthy volunteers. We also explored associations between hippocampal glutamate metabolites and glial activation, as indexed by [18F]FEPPA positron emission tomography (PET); symptom severity; and cognitive function. Groups differed significantly in glutamate plus glutamine (Glx) levels (F(2, 69) = 6.39, p = 0.003). Post-hoc analysis revealed that CHR had significantly lower Glx levels than both healthy volunteers (p = 0.003) and first-episode psychosis patients (p = 0.050). No associations were found between glutamate metabolites and glial activation. Our findings suggest that glutamate metabolites are altered in CHR.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1

a Voxel placement in the left hippocampus (30 × 14 × 10 mm3). b Typical spectrum of the left hippocampus LCModel output

Fig. 2

Scatter plots of a Glx (Glutamate + Glutamine) and b: Glu (Glutamate) in institutional units (IU) in the hippocampus of healthy volunteers (HV), clinical high risk (CHR) and first episode psychosis (FEP). CHR subjects that converted to psychosis after the study are shown as black squares. Group means are indicated by black bars. **Significance (p ≤ 0.05), *trend-level significance (0.05 < p < 0.1)