Psychological Medicine

Review Article

Meta-analysis of volumetric abnormalities in cortico-striatal-pallidal-thalamic circuits in major depressive disorder

E. Boraa1 c1, B. J. Harrisona1, C. G. Daveya1a2, M. Yücela1a2 and C. Pantelisa1

a1 Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, VIC, Australia

a2 Orygen Youth Health Research Centre, Melbourne, The University of Melbourne, VIC, Australia


Background Abnormalities in cortico-striatal-pallidal-thalamic (CSPT) circuits have been implicated in major depressive disorder (MDD). However, the robustness of these findings across studies is unclear, as is the extent to which they are influenced by demographic, clinical and pharmacological factors.

Method With the aim of clarifying these questions, we conducted a meta-analysis to map the volumetric abnormalities that were most robustly identified in CSPT circuits of individuals with MDD. A systematic search identified 41 studies meeting our inclusion criteria.

Results There were significant volume reductions in prefrontal (especially orbitofrontal) and anterior cingulate cortices, and also in subcortical structures such as the caudate nucleus and putamen, with effect sizes ranging from small to moderate. The subgenual anterior cingulate and orbitofrontal cortices were significantly smaller in antidepressant-free samples compared to medicated patients. Late-life depression (LLD) tended to be associated with smaller volumes in circumscribed frontal and subcortical structures, with the most robust differences being found in thalamic volume.

Conclusions Individuals with major depression demonstrate volumetric abnormalities of CSPT circuits. However, these observations may be restricted to certain subgroups, highlighting the clinical heterogeneity of the disorder. On the basis of this meta-analysis, CSPT abnormalities were more prominent in those with LLD whereas antidepressant use seemed to normalize certain cortical volumetric abnormalities.

(Received February 24 2011)

(Revised May 17 2011)

(Accepted August 01 2011)

(Online publication September 13 2011)


c1 Address for correspondence: Dr E. Bora, Alan Gilbert Building NNF level 3, Carlton 3053, Australia. (Email: