Major depressive disorder (MDD) has been related to structural brain characteristics that are correlated with the severity of disease. However, the correlation of these structural changes is less well clarified in treatment-resistant depression (TRD).

To summarise the existing literature on structural brain characteristics in TRD to create an overview of known abnormalities of the brain in patients with MDD, to form hypotheses about the absence or existence of a common pathophysiology of MDD and TRD.

A systematic search of PubMed and the Cochrane Library for studies published between 1998 and August of 2016 investigating structural brain changes in patients with TRD compared with healthy controls or patients with MDD.

Fourteen articles are included in this review. Lower grey matter volume (GMV) in the anterior cingulate cortex, right cerebellum, caudate nucleus, superior/medial frontal gyrus and hippocampus does not seem to differentiate TRD from milder forms of MDD. However, lower GMV in the putamen, inferior frontal gyrus, precentral gyrus, angular- and post-central gyri together with specific mainly parietal white matter tract changes seem to be more specific structural characteristics of TRD.

The currently available data on structural brain changes in patients with TRD compared with milder forms of MDD and healthy controls cannot sufficiently distinguish between a ‘shared continuum hypothesis’ and a ‘different entity hypothesis’. Our review clearly suggests that although there is some overlap in affected brain regions between milder forms of MDD and TRD, TRD also comes with specific alterations in mainly the putamen and parietal white matter tracts.

None.