Table 1.
Overview of ENIGMA MDD studies published to date.
| Study | Modality | Meta- or mega-analysis | Sample size | No. of cohorts | Main findings |
|---|---|---|---|---|---|
| Schmaal et al. 2016 in Molecular Psychiatry | sMRI (FreeSurfer subcortical volumes) | Meta | HC: 7199 MDD: 1728 | 15 | Mean hippocampal volume was significantly lower in MDD compared with HC. This effect was driven primarily by recurrence of MDD (i.e., >1 episode). MDD with an early age of onset (⩽21 years) showed significantly lower mean hippocampal volumes than HC. |
| Schmaal et al. 2017 in Molecular Psychiatry | sMRI (FreeSurfer cortical thickness and surface area) | Meta |
Adults: HC: 7658 MDD: 1902 Adolescents: HC: 294 MDD: 213 |
20 | Compared with adult HC, adults with MDD showed lower cortical thickness in the bilateral medial OFC, cingulate cortex, insula and temporal lobes, but no surface area alterations. Subgroup analysis revealed lower cortical thickness in adults with MDD with adult onset, but not adolescent onset, age of onset, relative to HC. Compared with adolescent HC, adolescents with MDD had lower total surface area (but no differences in cortical thickness), with most pronounced effects in medial OFC, superior frontal gyrus, and primary and higher order visual, somatosensory and motor areas. These effects were driven by adolescents with recurrent depression. |
| Renteria et al. 2017 in Translational Psychiatry | sMRI (FreeSurfer subcortical volumes) | Meta | HC: 1996 MDD: 1101 | 20 | No significant differences were found between MDD with suicidal ideation and HC. MDD with suicidal behavior (reported suicidal attempts or plans) showed a trend toward significant smaller ICV, compared with HC. No significant differences were found between MDD with and without suicidal ideation and/or behavior. |
| Frodl et al. 2017 in Journal of Psychiatry Research | sMRI (FreeSurfer subcortical volumes) | Mega | HC: 2078 MDD: 958 | 9 | Severity of childhood maltreatment (CM) was associated with lower caudate volumes in females, but no significant effects were found in males. The effect was associated with all subcategories of CM, but most pronounced for childhood emotional and physical neglect. The effect was independent of MDD diagnosis. |
| Tozzi et al. 2019 in Psychological Medicine | sMRI (FreeSurfer cortical thickness and surface area) | Mega | HC: 2588 MDD: 1284 | 12 | Regardless of MDD, overall severity of childhood maltreatment (CM) was associated with lower thickness in the supramarginal gyrus, banks of the superior temporal sulcus and lower surface area in the middle temporal lobe. Compared with no CM, the combination of childhood abuse and neglect showed lower cortical thickness in the same areas, in addition to the inferior parietal lobe, middle temporal lobe, and precuneus, whereas no effects were found for abuse or neglect alone. Males—but not females—with MDD and a history of CM showed greater surface area in the rostral ACC compared with the no CM group. The negative association between CM severity and thickness of various prefrontal, cingulate, and temporal regions was more pronounced with increasing age. No significant interaction effect between MDD diagnosis and CM. |
| de Kovel et al. 2019 in American Journal of Psychiatry | sMRI (FreeSurfer subcortical volumes, cortical thickness and surface area) | Mega |
Cortical regions: HC: 3504 MDD: 2256 Subcortical regions: HC: 4230 MDD: 2540 |
Cortical regions: 31 Subcortical regions: 32 |
No differences in the laterality of cortical regions thickness and surface area or subcortical volumes were found between MDD and HC. |
| Ho et al. 2020 in Human Brain Mapping | sMRI (FreeSurfer subcortical shapes) | Meta | HC: 2953 MDD: 1781 | 10 | Compared with HC, MDD had lower thickness and surface area in the subiculum and CA2/3 areas of the hippocampus and basolateral amygdala. These effects were primarily driven by MDD with an adolescent age of onset (⩽21 years). Recurrence of MDD was associated with lower surface area and thickness in the basolateral amygdala and in the CA1 region of the hippocampus. |
| Han et al. 2020 in Molecular Psychiatry | sMRI (FreeSurfer subcortical volumes, cortical thickness and surface area) | Mega | HC: 4314 MDD: 2675 | 19 | Compared with HC, MDD showed higher brain-PAD (brain-predicted age difference of 1.08 years). Strongest effects were found in MDD using antidepressants at time of scanning, patients in an active episode and patients in remission compared with HC, but there were no significant differences between the MDD subgroups. Brain-PAD was positive in all MDD subgroups, indicating that individuals with MDD were estimated to be older than expected based on the brain age model. |
| Van Velzen et al. 2019 in Molecular Psychiatry | DTI (FA, RD, MD and AD for atlas-defined white matter tracts of interest) | Meta |
Adults: HC: 1265 MDD: 921 Adolescents: HC: 290 MDD: 372 |
20 | Adults with MDD showed lower FA in 16 of the 25 WM tracts examined, relative to HC. These effects appeared to be global, with the corona radiate and the corpus callosum contributing most. The effects were mainly driven by recurrent MDD, MDD with adult age of onset (>21 years) and antidepressant-free patients at the time of scanning. Higher RD in adults with MDD was also observed across different ROIs. No differences were found between healthy adolescents and adolescents with MDD. |
DTI Diffusion tensor imaging, FA fractional anisotropy, HC healthy controls, ICV intracranial volume, MDD major depressive disorder, CM childhood maltreatment, OFC orbitofrontal cortex, ACC anterior cingulate cortex, RD radial diffusivity, MD mean diffusivity, AD axial diffusivity, ROIs regions of Interest, Brain-PAD brain-predicted age differencefractional anisotropy, sMRI structuralmagnetic resonance imaging, WM white matter.