Major depression is not a diagnosis, it is a departure point to differential diagnosis -- clinical and hormonal considerations (a commentary and elaboration on Antonejevic's paper).

Currently, the prevailing diagnostic systems of mental disorders, including Depressions and anxieties are based on descriptive phenomenological approach and not on etiology and pathophysiology. However, cumulative knowledge suggests that the field is moving towards establishment of subtypes or phenotypes of depressions based on different pathophysiologies, which may result in differential treatment responses. What is currently defined as 'Major Depressive Disorder (MDD)' may be the end-result of multiple heterogeneous biological and psychosocial processes. Therefore, MDD is actually a first step towards a differential diagnosis that eventually may lead to pathophysiology-based entities. Several hormonal systems may play a major role in the pathophysiology of several subtypes of depressions and anxieties. They include but are not limited to dysregulation of the hypothalamic-pituitary-adrenal (HPA) system, HP-Gonadal (HPG) and Thyroid (HPT) systems as well as their interactions with immune and other biological and psychosocial processes. Elucidation of the multiple underlying mechanisms of depressions and anxieties should lead to targeted treatment modalities and improvement of treatment responses.