Background: It is necessary to seek alternative therapies for depression, because side effects of medications lead to poor adherence and some patients do not achieve a clinical treatment effect. Recently the role of exercise as a low-cost and easy-to-use treatment for depression has gained attention with a number of studies showing that exercise is effective at reducing depressive symptoms and improving body functions such as cardiorespiratory system and cognitive function. Because of the heterogeneity of exercise therapy programs, there is no standardized and unified program. Few studies have summarized the specific properties of exercise programs (type, intensity, duration, and frequency) and clinical prescriptions for exercise are not mentioned in most articles.Aims: This study aimed to investigate the feasibility and efficacy of exercise therapy for patients with depression, in order to appraise the evidence and outline accepted guidelines to direct individualized treatment plans for patients with depression based on their individual situations.Methods: A systematic review of English language literature including papers published from 2010 to present in PubMed was performed. Given the feasibility of prescribing exercise therapy for patients with depression, nearly 3 years of clinical studies on the treatments of depressive symptoms with exercise were first reviewed, comparing the exercise programs utilized.Conclusions: Exercise has therapeutic effects on depression in all age groups (mostly 18–65 years old), as a single therapy, an adjuvant therapy, or a combination therapy, and the benefits of exercise therapy are comparable to traditional treatments for depression. Moderate intensity exercise is enough to reduce depressive symptoms, but higher-dose exercise is better for overall functioning. Exercise therapy has become more widely used because of its benefits to the cardiovascular system, emotional state, and systemic functions.Recommendations: Aerobic exercise/mind-body exercise (3–5 sessions per week with moderate intensity lasting for 4–16 weeks) is recommended. Individualized protocols in the form of group exercise with supervision are effective at increasing adherence to treatment.

Testosterone deficiency can lead to depressive symptoms in humans; however, the causes of this deficiency are incompletely understood. Here, we isolated Mycobacterium neoaurum from the fecal samples of testosterone-deficient patients with depression and showed that this strain could degrade testosterone in vitro. Furthermore, gavaging rats with M. neoaurum reduced their serum and brain testosterone levels and induced depression-like behaviors. We identified the gene encoding 3β-hydroxysteroid dehydrogenase (3β-HSD) as the enzyme causing testosterone degradation. Introducing 3β-HSD into Escherichia coli enhanced its ability to degrade testosterone. Gavaging rats with 3β-HSD-producing E. coli reduced their serum and brain testosterone levels and caused depression-like behaviors. Finally, compared with 16.67% of participants without depression, 42.99% (46/107) of the fecal samples of patients with depression harbored 3β-HSD, and 60.87% (28/46) of these fecal samples expressed 3β-HSD. These results suggest that 3β-HSD expressed by gut microbes may be associated with depressive symptoms due to testosterone degradation.

Background: Recently, depression has been identified as a prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the lipopolysaccharide (LPS)-induced sickness behavior in rats. Methods: Adult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally 1 h before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins. Results: The DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behavior rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1β in LPS-induced sickness behavior rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1. Conclusions: These findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behavior rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.