Basal glutamate in the hippocampus and the dorsolateral prefrontal cortex in schizophrenia: Relationships to cognitive proficiency investigated with structural equation modelling

Abstract

Objectives

Schizophrenia is characterised by deficits across multiple cognitive domains and altered glutamate related neuroplasticity. The purpose was to investigate whether glutamate deficits are related to cognition in schizophrenia, and whether glutamate-cognition relationships are different between schizophrenia and controls.

Methods

Magnetic resonance spectroscopy (MRS) at 3 Tesla was acquired from the dorsolateral prefrontal cortex (dlPFC) and hippocampus in 44 schizophrenia participants and 39 controls during passive viewing visual task. Cognitive performance (working memory, episodic memory, and processing speed) was assessed on a separate session. Group differences in neurochemistry and mediation/moderation effects using structural equation modelling (SEM) were investigated.

Results

Schizophrenia participants showed lower hippocampal glutamate (p = .0044) and myo-Inositol (p = .023) levels, and non-significant dlPFC levels. Schizophrenia participants also demonstrated poorer cognitive performance (p < .0032). SEM-analyses demonstrated no mediation or moderation effects, however, an opposing dlPFC glutamate-processing speed association between groups was observed.

Conclusions

Hippocampal glutamate deficits in schizophrenia participants are consistent with evidence of reduced neuropil density. Moreover, SEM analyses indicated that hippocampal glutamate deficits in schizophrenia participants as measured during a passive state were not driven by poorer cognitive ability. We suggest that functional MRS may provide a better framework for investigating glutamate-cognition relationships in schizophrenia.

Keywords:

• Schizophrenia
• hippocampus
• dlPFC
• glutamate
• MRS

Acknowledgements

None.

Statement of interest

None to declare.

Data availability statement

The ¹H MRS, MRI and cognitive performance data are available on request from the authors.

Additional information

Funding

The research was supported by the National Institute of Mental Health under the Award Number R01 MH111177 (JAS and VAD) and by the State of Michigan (Joe Young Sr./Helene Lycaki funds). The authors thank Caroline Zajac-Benitez and Jonathan Lynn for their assistance.