Gray matter correlates of MDD: a cross-cohort investigation of replicability and generalizability

COEX 

Major depressive disorder (MDD) is one of the leading causes of disability worldwide (1) and is still insufficiently treated, with approximately one third of patients being treatment-resistent (2). Despite the societal relevance of depression and a plethora of research over the past decades, the neurobiological underpinnings of the disorder are still poorly understood. Previous neuroimaging studies have yielded highly heterogeneous results, even across large consortia (3–5) and effect sizes appear to be subtle at most (6). In addition, the validity of brain-behavior findings in general have been questioned due to reports of underpowered study samples, overestimated effect sizes and overall low replicability (7). These findings make it highly relevant to systematically investigate the replicability of the neural correlates of psychiatric disorders, such as depression and assess their generalizability to independent cohorts.