Abstract
The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
Highlights
Major depressive disorder (MDD) is the single most common psychiatric disorder, affecting approximately 350 million people each year.[1]
We found significant and consistent thinner cortices in the frontal and temporal lobes of adult depressed patients (N = 1902) compared to controls (N = 7658) in the bilateral medial orbitofrontal cortex (OFC), fusiform gyrus, insula, rostral anterior and posterior cingulate cortex and unilaterally in the left middle temporal gyrus, right inferior temporal gyrus and right caudal anterior cingulate cortex (ACC)
Similar to the overall MDD group analysis, no cortical surface area differences were detected (Supplementary Tables S22–S24), and we found no significant correlations between thickness and surface area and the number of depressive episodes in recurrent patients (N = 496; Supplementary Table S10)
Summary
Major depressive disorder (MDD) is the single most common psychiatric disorder, affecting approximately 350 million people each year.[1] Even so, its pathogenesis and profile of effects in the brain are still not clear. In 2013, we initiated the MDD Working Group within the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium We reported subcortical volume differences between MDD patients and healthy controls that were related to clinical characteristics, based on data from 8927 individuals using an individual participant data-based meta-analysis approach. Subcortical volume differences were the greatest in the hippocampus, with the strongest effects in recurrent or early-onset patients.[2] Here we present results on cortical structural differences in an even larger sample (N = 10 105)
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