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Evaluating the evidence for biotypes of depression: attempted replication of Drysdale et.al. 2017

By Richard Dinga, Lianne Schmaal, Brenda Penninx, Marie Jose van Tol, Dick Veltman, Laura van Velzen, Nic van der Wee, Andre Marquand

Posted 14 Sep 2018
bioRxiv DOI: 10.1101/416321

Background: Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simultaneously using resting-state fMRI and clinical data and identified four distinct subtypes of depression with different clinical profiles and abnormal resting state fMRI connectivity. These subtypes were predictive of treatment response to transcranial magnetic stimulation therapy. Objective: Here, we attempted to replicate the procedure followed in the Drysdale et al. study and their findings in an independent dataset of a clinically more heterogeneous sample of 187 participants with depression and anxiety. We aimed to answer the following questions: 1) Using the same procedure, can we find a statistically significant and reliable relationship between brain connectivity and clinical symptoms? 2) Is the observed relationship similar to the one found in the original study? 3) Can we identify distinct and reliable subtypes? 4) Do they have similar clinical profiles as the subtypes identified in the original study? Methods: We followed the original procedure as closely as possible, including a canonical correlation analysis to find a low dimensional representation of clinically relevant resting state fMRI features, followed by hierarchical clustering to identify subtypes. We extended the original procedure using additional statistical tests, to test the statistical significance of the relationship between resting state fMRI and clinical data, and the existence of distinct subtypes. Furthermore, we examined the stability of the whole procedure using resampling. Results and Conclusion: We were not able to replicate the findings of the original study. Relationships between brain connectivity and clinical symptoms were not statistically significant and we also did not find clearly distinct subtypes of depression. We argue, that based on our rigorous approach and in-depth review of the original results, that the evidence for the existence of the distinct resting state connectivity based subtypes of depression is weak and should be interpreted with caution.

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