Citrate is Protective Against Chronic Stress in Females

Abstract

One of the most prevalent mental illnesses worldwide is Major Depressive Disorder (MDD). With high comorbidity to other mental disorders such as anxiety and bipolar disorder, untreated depression can lead to suicide. It has been well-established that women are more susceptible to depression than men, yet the underlying mechanisms behind these differences are still unclear. Treatment of MDD includes anti-depressant medication and psychotherapy. Lifestyle modifications such as adoption of a balanced diet and exercise can also have significant effects on the progression of the disease. Metabolites released by the liver and muscle after exercise such as beta-hydroxybutyrate and lactate have been shown to promote resilience to chronic stress and to act as antidepressants. In this study, we investigated whether a Kreb’s cycle metabolite, citrate, released into the circulation by the exercising muscle, can also serve as a novel treatment for MDD. We investigated the potential protective and antidepressant effects of citrate in female mice, and found that citrate can serve as a prophylactic treatment that promotes resilience to females subjected to Chronic Variable Stress (CVS).