Could Dietary Glutamate Play a Role in Psychiatric Distress?

Glutamate is an amino acid that functions as an excitatory neurotransmitter. It has also been associated with somatic and psychiatric distress and is implicated in the pathophysiology of psychiatric disorders such as schizophrenia. Ingestion of dietary glutamate, such as monosodium glutamate (MSG), has been mechanistically linked with greater distress among patients with chronic pain conditions, though findings have been equivocal. Preliminary research suggests that an MSG-restricted diet confers beneficial effects on somatic symptoms and well-being for some individuals with chronic pain conditions. In addition to associations with somatic distress, glutamate has been associated with the onset and progression of psychiatric symptoms. Thus, the role of dietary glutamate in psychiatric distress represents an underdeveloped and potentially important area for future research aimed at clarifying pathophysiological mechanisms and identifying targets for dietary intervention in psychiatric illnesses.

Metabolic syndrome is negatively associated with cognition among endothelial nitric oxide synthase (eNOS)- 786C carriers in schizophrenia-spectrum disorders.

Although metabolic syndrome and cognitive inefficiencies are well-described common complications of schizophrenia, their association remains inconsistent, potentially due to poorly understood mechanisms underlying their relationship. Variability in the endothelial nitric oxide synthase (eNOS) gene, specifically the T-786C variant, has been separately associated with cognition and metabolic syndrome, with worse outcomes for eNOS-786C carriers likely occurring via negative effects on blood vessel functioning. However, the interaction between eNOS and metabolic syndrome in cognition among adults with schizophrenia is unknown. This study aimed to test the main and interaction effects of the eNOS-786C allele in cognition using hierarchical regression analyses controlling for age, sex, education, race, and antipsychotic exposure. Metabolic syndrome, eNOS T-786C genotype, and cognitive performance were assessed in 226 community-dwelling participants with chronic schizophrenia-spectrum disorders. Results demonstrated a significant interaction between metabolic syndrome and the eNOS-786C allele. Specifically, among eNOS-786C carriers only, metabolic syndrome was independently associated with lower scores in processing speed and verbal fluency, and predicted 12.5% and 15.8% of variance in performance, respectively. These results suggest that the additive negative effects of eNOS-786C and metabolic syndrome on blood vessel functioning may be severe enough to negatively impact cognition. The finding that metabolic syndrome is associated with worse cognition only in the presence of the eNOS-786C allele may clarify extant inconsistencies in the literature. These findings provide preliminary evidence that may inform interventions to reduce cognitive morbidity among adults with schizophrenia.