An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective

Abstract

Major depressive disorder (MDD) is estimated to impose maximum debilitating effects on the society by 2030, with its critical effects on health, functioning, quality of life and concomitant high levels of morbidity and mortality. Yet, the disease is inadequately understood, diagnosed and treated. Moreover, with the recent drastic rise in the pace of life, stress has materialized as one of the most potent environmental factors for depression. In this scenario, it is important to understand the modern pathogenetic hypotheses and mechanisms, and possibly try to shift from the traditional approaches in depression therapy. These include the elaboration of pathophysiological changes in heterogeneous systems such as genetic, epigenetic, serotonergic, noradrenergic, gammaaminobutyric acid, glutamatergic and endocannabinoid systems, neurotrophic factors, HPA axis, immune system as well as cellular stress mechanisms. These components interact with each other in a complex matrix and further elucidation of their mechanism and cascade pathways are needed. This might aid in the identification of MDD subtypes as well as the development of sophisticated biomarkers. Further, characterization might also aid in developing multitargeted therapies that hold much promise as compared to the conventional monoamine based treatment. New candidate pharmacons, refined psychotherapeutic modalities, advanced neuro-surgical and imaging techniques as well as the implementation of pharmacokinetic, pharmacogenetic prescribing guidelines constitute the emerging expanses of MDD treatment.

Thalamo-Habenular Connection Differences Between Patients With Major Depressive Disorder and Normal Controls

“…MDD is the leading cause of severe functional impairment and poor quality of life due to symptoms such as depressed mood, loss of interest, sleep and appetite changes, hopelessness, feelings of guilt, and suicidal ideation lasting longer than two weeks (3)(4)(5). Therefore, MDD is a heterogeneous disorder in which several symptoms and signs appear due to various causes and include diverse neural tracts (6,7).…”

Discovering the Lost Reward: Critical Locations for Endocannabinoid Modulation of the Cortico–Striatal Loop That Are Implicated in Major Depression

“…According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [ 4 ], a major depressive episode is defined as a period of 2 weeks or longer during which there is either depressed mood or loss of interest or pleasure (i.e., anhedonia) and four additional symptoms reflecting changes in activity, e.g., psychomotor agitation, retardation or fatigue, change in sleep patterns and suicidality. This disorder is complex, and its etiology, which may include social and psychological factors such as stressful or traumatic events [ 5 , 6 ], inflammation and microbiome [ 7 , 8 , 9 ], in addition to epigenetic and genetic ones and age-related factors [ 10 , 11 , 12 , 13 ], remains unclear to date [ 14 ]. Depressive symptoms may be reduced within several weeks after the start of conventional antidepressants, but treatment resistance concerns one-third of the patients who fail to achieve recovery.…”

Antidepressant-Like Effect of Geniposide in Mice Exposed to a Chronic Mild Stress Involves the microRNA-298-5p-Mediated Nox1

“…Worse still, comorbid depression has been reported to enhance the morbidity rate of stroke, cardiovascular diseases, diabetes, and obesity (Penninx et al, 2013 ). With the dramatic acceleration in the pace of life in modern society, stress has become one of the most common environmental factors that cause depression (Athira et al, 2019 ). To date, the optimal choice in the treatment of depression is antidepressants (Kok and Reynolds, 2017 ).…”