INTRODUCTION
With a lifetime prevalence of 416%,1 major depressive disorder (MDD) is a very common psychiatric disease and is among the leading causes of disability worldwide.2 Despite intensive research aimed at identifying neurobiological substrates of depression in the last decades, our understanding of the pathophysiological mechanisms underlying depression is still rudimentary. Widely available structural magnetic resonance imaging has led to hypotheses of (para-)limbic circuits being involved in MDD, but still the exact pattern of structural brain alterations associated with MDD remains unresolved, perhaps due to small sample sizes, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. Therefore, in the current study we meta-analyzed structural magnetic resonance imaging data of a very large sample (n = 8927) to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls.
Many studies have found structural alterations in various subcortical brain regions in MDD. To date, volumetric differences have not always been consistent and are poorly replicated for some regions; moreover, sample sizes are often small, limiting the power to detect subtle brain differences. Meta–analyses represent useful tools to identify the most robust findings across studies, and indicate that morphological changes in MDD are regional rather than global.3–5 Hippocampal volume reduction (one of the most extensively studied regions) in MDD has been one of the most widely replicated findings.3 However, the association between MDD and hippocampal volume reduction is likely complex, and hippocampal volumes may be smaller, on average, in patients with recurrent MDD compared to patients early in the course of adult-onset MDD.6 Other factors may modulate the effect size of morphological changes in the hippocampus in MDD, including disease severity, childhood maltreatment, age of onset, antidepressant medication and illness duration