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
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.