Data Sharing of the REST-meta-MDD Project from the DIRECT Consortium

(Note: Part of the content of this post was adapted from the original DIRECT Psychoradiology paper (https://academic.oup.com/psyrad/article/2/1/32/6604754) and REST-meta-MDD PNAS paper (http://www.pnas.org/cgi/doi/10.1073/pnas.1900390116) under CC BY-NC-ND license.)

Major Depressive Disorder (MDD) is the second leading cause of health burden worldwide (1). Unfortunately, objective biomarkers to assist in diagnosis are still lacking, and current first-line treatments are only modestly effective (2, 3), reflecting our incomplete understanding of the pathophysiology of MDD. Characterizing the neurobiological basis of MDD promises to support developing more effective diagnostic approaches and treatments.

An increasingly used approach to reveal neurobiological substrates of clinical conditions is termed resting-state functional magnetic resonance imaging (R-fMRI) (4). Despite intensive efforts to characterize the pathophysiology of MDD with R-fMRI, clinical imaging markers of diagnosis and predictors of treatment outcomes have yet to be identified. Previous reports have been inconsistent, sometimes contradictory, impeding the endeavor to translate them into clinical practice (5). One reason for inconsistent results is low statistical power from small sample size studies (6). Low-powered studies are more prone to produce false positive results, reducing the reproducibility of findings in a given field (7, 8). Of note, one recent study demonstrate that sample size of thousands of subjects may be needed to identify reproducible brain-wide association findings (9), calling for larger datasets to boost effect size. Another reason could be the high analytic flexibility (10). Recently, Botvinik-Nezer and colleagues (11) demonstrated the divergence in results when independent research teams applied different workflows to process an identical fMRI dataset, highlighting the effects of “researcher degrees of freedom” (i.e., heterogeneity in (pre-)processing methods) in producing disparate fMRI findings.

To address these critical issues, we initiated the Depression Imaging REsearch ConsorTium (DIRECT) in 2017. Through a series of meetings, a group of 17 participating hospitals in China agreed to establish the first project of the DIRECT consortium, the REST-meta-MDD Project, and share 25 study cohorts, including R-fMRI data from 1300 MDD patients and 1128 normal controls. Based on prior work, a standardized preprocessing pipeline adapted from Data Processing Assistant for Resting-State fMRI (DPARSF) (12, 13) was implemented at each local participating site to minimize heterogeneity in preprocessing methods. R-fMRI metrics can be vulnerable to physiological confounds such as head motion (14, 15). Based on our previous work examination of head motion impact on R-fMRI FC connectomes (16) and other recent benchmarking studies (15, 17), DPARSF implements a regression model (Friston-24 model) on the participant-level and group-level correction for mean frame displacements (FD) as the default setting.

In the REST-meta-MDD Project of the DIRECT consortium, 25 research groups from 17 hospitals in China agreed to share final R-fMRI indices from patients with MDD and matched normal controls (see Supplementary Table; henceforth “site” refers to each cohort for convenience) from studies approved by local Institutional Review Boards. The consortium contributed 2428 previously collected datasets (1300 MDDs and 1128 NCs). On average, each site contributed 52.0±52.4 patients with MDD (range 13-282) and 45.1±46.9 NCs (range 6-251). Most MDD patients were female (826 vs. 474 males), as expected. The 562 patients with first episode MDD included 318 first episode drug-naïve (FEDN) MDD and 160 scanned while receiving antidepressants (medication status unavailable for 84). Of 282 with recurrent MDD, 121 were scanned while receiving antidepressants and 76 were not being treated with medication (medication status unavailable for 85). Episodicity (first or recurrent) and medication status were unavailable for 456 patients.

To improve transparency and reproducibility, our analysis code has been openly shared at https://github.com/Chaogan-Yan/PaperScripts/tree/master/Yan_2019_PNAS. In addition, we would like to share the R-fMRI indices of the 1300 MDD patients and 1128 NCs through the R-fMRI Maps Project (http://rfmri.org/REST-meta-MDD). These data derivatives will allow replication, secondary analyses and discovery efforts while protecting participant privacy and confidentiality.

According to the agreement of the REST-meta-MDD consortium, there would be 2 phases for sharing the brain imaging data and phenotypic data of the 1300 MDD patients and 1128 NCs. 1) Phase 1: coordinated sharing, before January 1, 2020. To reduce conflict of the researchers, the consortium will review and coordinate the proposals submitted by interested researchers. The interested researchers first send a letter of intent to rfmrilab@gmail.com. Then the consortium will send all the approved proposals to the applicant. The applicant should submit a new innovative proposal while avoiding conflict with approved proposals. This proposal would be reviewed and approved by the consortium if no conflict. Once approved, this proposal would enter the pool of approved proposals and prevent future conflict. 2) Phase 2: unrestricted sharing, after January 1, 2020. The researchers can perform any analyses of interest while not violating ethics.

The REST-meta-MDD data entered unrestricted sharing phase since January 1, 2020. The researchers can perform any analyses of interest while not violating ethics. Please visit Psychologcial Science Data Bank: (http://doi.org/10.57760/sciencedb.o00115.00013) to download the data, and then sign the Data Use Agreement and email the scanned signed copy to rfmrilab@gmail.com to get unzip password and phenotypic information.

ACKNOWLEDGEMENTS

This work was supported by the National Key R&D Program of China (2017YFC1309902), the National Natural Science Foundation of China (81671774, 81630031, 81471740 and 81371488), the Hundred Talents Program and the 13th Five-year Informatization Plan (XXH13505) of Chinese Academy of Sciences, Beijing Municipal Science & Technology Commission (Z161100000216152, Z171100000117016, Z161100002616023 and Z171100000117012), Department of Science and Technology, Zhejiang Province (2015C03037) and the National Basic Research (973) Program (2015CB351702).

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Supplementary Table. Samples of the REST-meta-MDD project, consortium sites, contributors, sample size, data acquisition parameters, and published studies based on the present cohorts.

Abbreviations: MDD, major depressive disorder; NC, normal control.