ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Abstract

A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of largescale data sharing for mental health research.

Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure

“…Together, these results suggest that the spatial correspondence between group-level deviations for two clinically dissimilar disorders was explained by overall psychopathology. Previous studies have revealed non-uniform gray matter reductions concentrated in vmPFC/mOFC, inferior temporal, daCC and insular cortices across major depressive, bipolar, schizophrenia, and anxiety disorders (35)(36)(37)(38)(39)(40). Here, we found that deviations in each of these regions were implicated most strongly by overall psychopathology.…”

“…First, given that psychopathology may have neurodevelopmental origins, we tested the primary hypothesis that modeling cortical volume according to deviations from normative neurodevelopment would provide improved out-ofsample prediction of psychopathology compared to using raw volume. Second, at the regional level, we expected that overall psychopathology would explain the common abnormalities observed in the case-control literature (35)(36)(37)(38)(39)(40); we specifically predicted that greater overall psychopathology would be associated with greater negative deviations (i.e., lower than normative cortical volume) in the vmPFC/mOFC, inferior temporal, daCC, and insular cortices. These regions were selected based on their consistent implication across multiple distinct clinical disorders in both high-powered case-control studies (35)(36)(37)(38)(39)(40) and meta-analyses (39).…”

“…Second, at the regional level, we expected that overall psychopathology would explain the common abnormalities observed in the case-control literature (35)(36)(37)(38)(39)(40); we specifically predicted that greater overall psychopathology would be associated with greater negative deviations (i.e., lower than normative cortical volume) in the vmPFC/mOFC, inferior temporal, daCC, and insular cortices. These regions were selected based on their consistent implication across multiple distinct clinical disorders in both high-powered case-control studies (35)(36)(37)(38)(39)(40) and meta-analyses (39). Additionally, supporting the notion that effects in these regions predominantly represent disorder-general rather than disorder-specific biomarkers, we also predicted that correlations between deviations in these regions and overall psychopathology would be stronger than correlations between deviations and the specific dimensions in our model (e.g., externalizing, psychosis).…”

Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications

“…The most important and promising studies were conducted by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, which investigated the human brain across 43 countries. The ENIGMA-MDD Working Group was launched in 2012 to detect the structural and functional changes associated with MDD reliably and replicate them in various samples around the world [128]. So far, the ENIGMA-MDD Working Group has collected data from 4,372 MDD patients and 9,788 healthy controls across 14 countries, including 45 cohorts [128].…”

Schema therapy versus cognitive behavioral therapy versus individual supportive therapy for depression in an inpatient and day clinic setting: study protocol of the OPTIMA-RCT

“…Neuroimaging in the context psychotherapy research regarding MDD is built on evidence that the clinically heterogeneous condition of MDD is reflected in structural and functional abnormalities of brain circuits [168,169]. These abnormalities, on one hand, represent target systems that are modified by the learning processes stimulated by psychotherapy.…”