The cognitive metabolomic signatures in schizophrenia spectrum disorders: A systematic review

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BACKGROUND: Understanding the metabolome, the metabolite profile within biological samples, can provide insight into the mechanisms and processes underlying schizophrenia spectrum disorders (SSDs). Given that cognitive impairments are a core symptom domain of SSDs, investigating metabolomic alterations and their associations with cognitive impairments may help uncover pathways and mechanisms, with the potential to provide future treatments. Currently, there are no systematic reviews exploring the associations between cognition and metabolomic signatures. Therefore, the objective of this systematic review is to identify and examine these associations. METHOD: A systematic database search was conducted in Ovid MEDLINE, EMBASE and Scopus for studies related to the following three conceptual domains: "schizophrenia spectrum disorders", "metabolomics", and "cognition." Studies with a case-control component and/or association analyses were included in the review. Risk of bias assessments were conducted using the appropriate Johanna Briggs Institute Critical Appraisal Tool. RESULTS: Nine studies met inclusions for this review. Within these studies, 44 metabolites were identified as being dysregulated in cognitively impaired individuals with SSDs as compared to cognitively normal patients; 38 metabolites were downregulated while 6 were upregulated. The most frequently dysregulated classes of metabolites were carboxylic acids and derivatives, organooxygen compounds, and fatty acyls. For the association analyses, a mixture of positive and negative associations was found between cognition and metabolites, and the metabolite classes mainly dysregulated were glycerophospholipids, glycerolipids and fatty acyls. CONCLUSION: The identified metabolites may impact pathways related to inflammation, glutamate and glutamine metabolism, and lipid metabolism which may have an influence on cognition impairment in SSDs.

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