Can melatonin improve the alteration of protein synthesis occurring in schizophrenia and bipolar disorder?

The prevalence of mental illnesses has significantly increased globally in recent decades due to multifactorial causes. Of these, schizophrenia and bipolar disorder, due to their high incidence and high associated disability, stand out. However, the effective treatments on these disorders are lagged behind their increased incidence. Melatonin, as an essential molecule in the regulation of sleep-wake rhythm and the naturally occurring antioxidant, has only received attention for the treatment of such psychiatric disorders in relation to its circadian rhythm regulation, but its overwhelming role as a regulator of oxidative stress that facilitates the amelioration of neuronal damage has not been addressed for this respect. In this communication, the novel aspects of melatonin on mental illnesses have been discussed. We provide the necessary literature to justify the beneficial roles and the mechanisms of melatonin to treat schizophrenia and bipolar disorder. These mechanisms include that melatonin enhances reticulum stress, potentiates the unfolded protein response, and increases endoplasmic reticulum synthesis to facilitate autophagy and even suppresses apoptosis. This process involves not only the expected organelles but is a more complex cohesion that even includes the mitochondria, a well-known target of melatonin, which reinforces the robustness of our hypothesis, i.e., melatonin prevents the development of protein aggregates and abnormal structures typically observed in brain damage. Its documented capacity and the need to improve treatment efficiency in a growing population afflicted by mental illnesses are the basis of this hypothesis and support a role of melatonin, as antioxidant, in psychiatric disorders.