Dear Colleagues,

Major depressive disorder is a major source of disease burden whose impact is continuing to rise. Indeed, the recent COVID-19 pandemic was accompanied by a major increase in the prevalence of cases worldwide. Beyond the morbidity and mortality associated with depression, this disorder is also linked to the exacerbation of other conditions. Although effective pharmacological and non-pharmacological interventions are available, approximately 30-60% patients are non-responsive or only partially responsive to treatment. The availability of response biomarkers could speed up recovery and spare patients the toxicity of ineffective treatments. Moreover, diagnostic biomarkers could assist with the diagnosis of depression, which currently relies solely on questionnaire tools. However, a better understanding of the biological basis of major depression is needed to develop new approaches to diagnosis and treatment. During the last 50 years, a number of mechanisms have been linked to the pathophysiology of major depression. These include monoaminergic dysregulation, hypothalamic–pituitary–adrenal axis dysfunction, impairment of neurogenetic and neurotrophic pathways, glutamatergic and GABAergic alterations, neuroinflammatory activation, and changes in neuropeptide signalling. Nevertheless, much still remains to be discovered and the identification of new targets for pharmacological intervention will require a much better comprehension of the molecular pathophysiological basis of major depressive disorder. This issue will report studies that shed new light on the molecular basis of major depression, as well as on peripheral biomarkers for personalized medicine. Studies in both humans and animal models are welcome.

Dr. Lucia Carboni
Guest Editor