The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder

Abstract

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

Keywords: DIRECT; R-fMRI; database; major depressive disorder; neuroimaging.

Figure 1:

Principal findings from DIRECT studies. (A) Reduced FC within the DMN is revealed in patients with MDD compared to HCs (Yan et al., 2019). (B) Both decreased global efficiency (E_glob) and local efficiency (E_loc) are found in MDD vs. HC contrast (Yang et al., 2021). (C) Alterations in terms of temporal dynamic properties (increased variability, decreased temporal correlation coefficient, and characteristic temporal path length) are observed in patients with MDD as compared to HCs (Long et al., 2020). (D) Altered PAS scores are primarily observed in DMN (red), VN (blue), FPCN (yellow), and ventral and dorsal attention network (green) in MDD vs. HC contrast (Ding et al., 2021). (E) Reduced VMHC was found in DMN, VN, and SMN regions in MDD vs. HC contrast (Deng et al., 2021). (F) Patients with MDD can be clustered into two subgroups according to FCs within DMN (Liang et al., 2020). (G) Temporal and occipital regions, thalamus, prefrontal, and postfrontal gyrus show difference in GMV among GI, non-GI MDD patients, and HCs (Liu et al., 2021). Abbreviations: PAS, parameter of asymmetry; GI, gastrointestinal; MDD, major depressive disorder; HC, healthy control; DMN, default mode network; VN, visual network; FPCN, fronto-parietal control network; SMN, somato-motor network; FC, functional connectivity; VMHC, voxel-mirrored homotopic connectivity.