An Overview of Disease and Health Research Vol. 11

Major Depressive Disorder has become a significant public health issue that deeply impacts an individual's life.  Depression is a multifactorial psychiatric disease and the leading cause of distress, disability, and suicide. Reduced quality of life is evident owing to a disease and its comorbidities, as well as social factors. However, several hypotheses have been proposed to explain the pathogenesis of MDD. This narrative review discusses the multifactorial origin of major depressive disorder resulting from interactions among genetic, environmental, psychological, and biological factors.

Research in these areas continues and increasingly connects to neuroinflammatory processes that impact brain cells and structures. The current understanding of MDD's pathophysiology highlights the impact of cytokines in mood regulation, as well as the limbic system structures, including the amygdala, hippocampus, and prefrontal cortex, all of which are affected. The review further offers insights into the hyperactivation of the hypothalamic–pituitary–adrenal axis, monoamine theories of depression, the kynurenine pathway, hormonal dysregulations, neuroplasticity, environmental stressors, and other factors. Systemic stress, whether acute or chronic, and the involvement of the immune response underpin cognitive and emotional processes in patients with depression.

Neurotransmitter imbalances are currently a key focus of pharmacotherapy, and antidepressant medications influence the activity of common neurotransmitters. The review further informs the identification of new targets for pharmacotherapy and other therapies in patients with neuroinflammation who cannot respond to current treatments.