Altered resting-state functional connectome in major depressive disorder : a mega-analysis from the PsyMRI consortium

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers (). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 +/- 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 +/- 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.Funding Agencies|German Research Foundation (DFG)German Research Foundation (DFG) [KR 3822/7-1, KR 3822/7-2, FOR2107 KI588/14-1, FOR2107 KI588/14-2, FOR2107 NE2254/2-1, FOR2107 NE2254/3-1, FOR2107 DA1151/5-1, DA1151/5-2, HA7070/2-2, HA7070/3, HA7070/4]; German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)German Research Foundation (DFG) [SFB779-A06]; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [KLI 597-B27, KLI-148-B00, F3514-B11]; Health Research Board (HRB) Ireland; Science Foundation Ireland (SFI)Science Foundation Ireland; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [GNT1176689]; National Health and Medical Research Council of Australia (NHMRC)National Health and Medical Research Council of Australia [510135, 1037196]; German Research FoundationGerman Research Foundation (DFG) [GR 4510/2-1]; European CommissionEuropean CommissionEuropean Commission Joint Research Centre [H2020-634541]; Australian National Health and Medical Research Council of Australia (NHMRC)National Health and Medical Research Council of Australia [1064643, 1024570]; NHMRC Career Development FellowshipsNational Health and Medical Research Council of Australia [1061757, 1124472]; Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Munster [Dan3/012/17, MzH 3/020/20]; AOP Orphan; Medizin Medien Austria; Vertretungsnetz; Schwabe Austria; JanssenJohnson & JohnsonJohnson & Johnson USAJanssen Biotech Inc; Angelini