Brain Cortical Thinning and Surface Area Reductions in Major Depressive Disorder

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Age-dependent structural brain abnormalities identified in adolescents and adults with major depressive disorder.
Age-dependent structural brain abnormalities identified in adolescents and adults with major depressive disorder.

Adolescents and adults diagnosed with major depressive disorder (MDD) have widespread brain region abnormalities such as cortical thinning and surface area reductions compared with healthy control participants, a new meta-analysis of more than 10 000 people reveals.1

Published in Molecular Psychiatry, the ENIGMA-MDD study was led and co-authored by Lianne Schmaal, PhD, at the VU University Medical Center in Amsterdam, The Netherlands, and is part of a wider international collaborative effort of the ENIGMA-MDD Working Group.

Depression affects approximately 350 million people worldwide each year and is the leading cause of disability.2 New research efforts are illuminating the neurocircuitry that underlies mood disorders, and are helping identify potential genetic, neural, environmental, and behavioral markers of MDD.3 Although structural brain abnormalities that are associated with MDD have previously been identified, multisite studies with higher statistical power are needed to improve the search for neuroimaging biomarkers of disease risk, clinical course, and treatment outcome of MDD.4

In the largest study to date, Dr Schmall, and her team of researchers, used T1-weighted magnetic resonance imaging (MRI) brain scans from 2 148 patients with MDD and 7 957 healthy individuals to conduct a meta-analysis of the evidence for the association between MDD and cortical thickness and surface area. They examined the adolescent and adult data separately because previous studies identified age-dependent brain structure abnormalities in individuals with MDD.1 For example, the same group previously reported that, relative to control participants, patients diagnosed with recurrent and/or early-onset MDD have a smaller hippocampus, the part of the brain primarily associated with the formation of long-term memories and spatial navigation.5 Also, until now, cortical surface area abnormalities have not been examined in adolescents with MDD.

Overall, compared with healthy adolescents, Dr Schmall and colleagues found reductions in both left and right hemisphere total surface area, as well as surface area reductions in numerous brain regions, of adolescent patients with MDD. More specifically, they observed regional surface area reductions in the frontal lobe, and in somatosensory and motor areas. The strongest effects were observed in adolescent patients with recurrent MDD. They did not, however, observe surface area abnormalities in adults with MDD.1

With regard to cortical thickness, the results are in line with previous reports and indicate that adults with MDD have cortical thickness deficits in the frontal lobe, compared with healthy adults. Also, the findings indicate, for the first time, a cortical thinning of the temporal lobe in adults with MDD. The strongest effects were observed in adult patients with adult-onset MDD.

“Cortical thickness and surface area represent distinct morphometric features of the cortex and may be differentially affected by depression at various stages of life,' the authors concluded in the publication.


1. Schmaal L, Hibar DP, Sämann PG, et al. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Mol Psychiatry. 2016. doi: 10.1038/mp.2016.60. [Epub ahead of print]

2. World Health Organization. Depression: a global public health concern, 2012. Available at: http://wfmh_2012.pdf (accessed 31 May 2016).

3. Saveanu RV, Nemeroff CB. Etiology of depression: genetic and environmental factors. Psychiatr Clin North Am. 2012;35:51-71.

4. Lener MS, Iosifescu DV. In pursuit of neuroimaging biomarkers to guide treatment selection in major depressive disorder: a review of the literature. Ann N Y Acad Sci. 2015;1344:50-65.

5. Schmaal L, Veltman DJ, van Erp TG, et al. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Mol Psychiatry. 2016;21:806-812.

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