Mechanisms and Effects of Dietary Restriction on CNS and Affective Disorders

Neuropsychiatric disorders, including depression contribute significantly to global disability and possess high social and health burden. Management is dominated by pharmacotherapy and psychotherapy; nevertheless, such treatments prevent or treat less than half of the patients, suggesting that alternative approaches are required. Emerging data suggest that diet may be an adjustable risk factor for psychiatric disorders. Caloric restriction (CR) possesses protective effects in almost all organs including the brain. However, the precise molecular pathways of these effects remain uncertain. In this review, we will discuss the putative neurobiological mechanisms of CR on the brain. The article will address also the molecular basis of the antidepressant effects of CR, primarily including ghrelin signaling, CREB neurotropic effects and ketone bodies production. Then we will highlight the probable effect of CR on the neuroinflammation, which emerges as a key pathogenetic factor for the majority of neuropsychiatric disorders. Finally, we discuss the so called caloric restriction mimetics, compounds that reproduce properties of CR. Further research will be required to verify the safety and efficacy of CR before a general approval can be proposed to introduce it and its mimetics in clinical practice for the treatment of neuropsychiatric disorders.