The Effects of Calorie Restriction in Depression and Potential Mechanisms

Depression, also called major depressive disorder, is a neuropsychiatric disorderjeopardizing an increasing number of the population worldwide. To date, a large number of studieshave devoted great attention to this problematic condition and raised several hypotheses ofdepression. Based on these theories, many antidepressant drugs were developed for the treatment ofdepression. Yet, the depressed patients are often refractory to the antidepressant therapies. Recently,increasing experimental evidences demonstrated the effects of calorie restriction in neuroendocrinesystem and in depression. Both basic and clinical investigations indicated that short-term calorierestriction might induce an antidepressant efficacy in depression, providing a novel avenue for treatment. Molecular basisunderlying the antidepressant actions of calorie restriction might involve multiple physiological processes, primarilyincluding orexin signaling activation, increased CREB phosphorylation and neurotrophic effects, release of endorphin andketone production. However, the effects of chronic calorie restriction were quite controversial, in the cases that it oftenresulted in the long-term detrimental effects via inhibiting the function of 5-HT system and decreasing leptin levels. Herewe review such dual effects of calorie restriction in depression and potential molecular basis behind these effects,especially focusing on antidepressant effects.