Abstract

Background: The diagnosis of depression is not only highly prevalent but also remarkable heterogeneous symptomatically. Only a few symptoms are considered common to most presentations of depression, while others form various combinations to define subtypes of depressive disorder. Most antemortem neuroimaging studies and postmortem neurochemical and cellular research have demonstrated significant structural, functional and cellular alterations shared by a majority of subjects with depression. However, it seems very likely that identifying relevant etiological factors and cellular mechanisms associated with the specific neuropathology of depression subtypes may help to focus or individualize depression treatments.

Objective: The main aim of this review article is to point to the need of studying those differential cellular mechanisms characterizing different subtypes of depression as they relate to relevant neural circuits.

Method: The review is based on a literature search using mainly PubMed and Google Scholar databases. Articles were considered relevant if they contained studies relating depression subtypes (or distinct symptom clusters) to neuroimaging or neuropathological parameters.

Results and Conclusions: Antemortem quantification in psychiatric diagnostic scales and neuroimaging studies, with their larger number of subjects, have started to identify functional differences that discriminate depression subtypes. However, characterization of cellular and neurochemical pathology in neurons and glial cells has yet to be directed to uncover molecular and cellular mechanisms in relevant brain centers and circuits differentially affected in depression subtypes. Identifying these mechanisms will depend on our ability to first sort out cellular alterations by combining postmortem and animal model studies of depression subtypes.

Keywords: Depression, pathology, neuroimaging, neuroanatomy, subtypes, glia.