Central glutathione mitigates obesity-induced social phobia: evidence from human and animal studies.

Abstract

OBJECTIVE: To explore the impact of obesity on social phobia and the therapeutic effect of the antioxidant glutathione on this disorder. METHODS: A total of 600 subjects were divided into an Obese Group and a Control Group. Four scales were utilized to determine social phobia, and magnetic resonance spectroscopy was applied to evaluate the central glutathione levels. Multivariate logistic regression was used for analysis. A mouse obesity model was subsequently established using a high-fat diet. Agonists or inhibitors were used to upregulate or downregulate hippocampal glutathione. The social interaction test was used to evaluate the social phobia of the mice, and the ELISA method was used to measure the levels of oxidative stress indicators in the hippocampus. Anova was used for analysis. RESULTS: Compared with the control subjects, obese subjects had higher social phobia scores. A higher central glutathione level was associated with a lower social phobia score. In the animal experiments, obese mice exhibited more social phobia behaviours. When the glutathione level in the hippocampus was increased and decreased, the oxidative stress level in the hippocampus of the mice decreased and increased accordingly, whereas social phobia behaviours were alleviated and exacerbated, respectively. CONCLUSION: Obesity may induce social phobia. However, the antioxidant glutathione attenuates the central oxidative stress response and alleviates obesity-related social phobia.