Nocturnal light exposure aggravates schizophrenia via gut microbiota mediated lipid metabolism: Human and animal multi-omics evidence.

BACKGROUNDArtificial light at night (ALAN) is common in psychiatric inpatient settings, yet evidence suggests it may exacerbate mental disorders. We aimed to examine the effects of ALAN intervention on schizophrenia relapse risk and the mediating roles of gut microbiota and metabolic pathways.

METHODSSchizophrenia patients in hospital rooms randomly received usual ALAN or reduced ALAN by partially covering lights, and swapped after a two-week washout interval. Outcomes were assessed using the Early Signs Scale (ESS) and Montreal Cognitive Assessment (MoCA). Complementary experiments in a dizocilpine-induced schizophrenia mouse model under ALAN exposure evaluated gut microbiota, metabolomic profiles, and behavioral effects following linoleic acid supplementation.

RESULTSReduced ALAN exposure was associated with lower ESS scores on depression and incipient psychosis, as well as higher scores on MoCA. These benefits were linked to stabilized gut microbiota and linoleic acid metabolism. There were mediation effects by 13(S)-HpODE (linoleic acid metabolite) on associations of ALAN with higher depression and lower MoCA scores. Mice exposed to ALAN showed gut dysbiosis, disrupted linoleic acid metabolism, and schizophrenia-like behaviors, which were partially ameliorated by linoleic acid supplementation.

CONCLUSIONSALAN exposure may increase the risk of schizophrenia relapse, potentially mediated by gut microbiota and linoleic acid metabolism. Linoleic acid supplementation indicates potential benefits in rodent models, suggesting a potential translational intervention worthy of further investigation.