Study of Neuroendocrine-Immune Interactions in Major Depression to Develop More Efficient Therapeutic Options

Major depressive disorderMajor depressive disorder (MDD) is a mood disorderMood disorder characterized by constant feelings of sadness and anhedonia that has become a global health emergency according to the World Health OrganizationWorld Health Organization (WHO). It affects 280 million people worldwide and is a leading cause of disability and economic loss. There are a variety of therapeutic options for patients with MDD, however, according to some studies, the treatmentTreatment of MDD has a high failure rate. There are multiple hypotheses to explain MDD, in which several systems are involved, such as the neuroendocrine and immune systems. Patients with MDD present immunoendocrine alterations, such as cortisolCortisol resistance and inflammation, which are associated with alterations in neurotransmitterNeurotransmitter metabolism, such as decreased serotoninSerotonin and increased kynureninesKynurenine metabolites in the brain and periphery. Inflammation has become an important target of new treatmentsTreatment for MDD. Extracellular monomeric ubiquitin (ECMU) is a molecule that has been shown to have immunomodulatory effects through modulation of cholinergic tone, causing a decrease in proinflammatory cytokines such as IL-6Interleukin-6 and TNF-α. In this chapter, we put into perspective the influence of the inflammatory response in MDD and comment on our experience of using ECMU as a concomitant treatmentTreatment with selective serotonin reuptake inhibitorsSelective serotonin reuptake inhibitors (SSRIs). This chapter explores the evidence suggesting that ECMU can be used for the treatmentTreatment of MDD. ECMU has been described to potentiate the effect of SSRIs in patients with depression by causing a decrease in cortisolCortisol and an improvement in immune system functioning. MDD has a complex pathophysiology involving alterations in multiple systems and is associated with a high rate of therapeutic failure, requiring the development of multidisciplinary treatmentsTreatment focused on ameliorating inflammatory, endocrine, and neurochemical alterations.