New review with @EikoFried and @karmelchoi in @hmg_journal on #heterogeneity in #depression - we identified three sources of #heterogeneity in #depression in #genetic studies (mostly from past 10 yrs): operationalization, manifestations and etiology. https://tinyurl.com/y5mkfmp3  (1/8)

Operationalisation pertains to how we do #science. #depression has been defined/measured differently in diff. studies, relying on diff. criteria and identifying non-overlapping sets of cases. Referring to all of them as ‘major depression’ obfuscates important differences. (2/8)

Manifestations encompass differences in symptoms, severity, developmental timing, comorbidities and physiology - cases may differ dramatically in these respects. We identify subtypes using manifestations through clinical experience or, increasingly, #data-driven means. (3/8)

Etiology has to do with the combination of #genetic, #environmental and other factors leading to one’s disease, as well as their interactions. In particular, trying to disentangle effects of diverse environments from heterogeneous genetic effects is very challenging. (4/8)

As depression may reflect several highly heterogeneous phenotypes, and it is difficult to agree upon a single construct that can be consistently measured, #splitting (study symptoms) or #lumping (study transdiagnostic factors) may be two productive ways forward. (5/8)

Overall, we found that heterogeneity in operationalizations of #depression affect studies on heterogeneity in #depression manifestations and etiology, and is a considerable source of inconsistency. Even the best methods can't overcome missing and inconsistent data. (6/8)

Which is why our first two recommendations are 1) measuring more and 2) measuring consistently. Also, we can't stay in a mono-disciplinary vacuum - we need to 3) #collaborate with clinicians and other experts, and 4) follow up on our results with functional studies. (7/8)

It was a great experience working with @EikoFried and @karmelchoi - I also miss our friday evening discussions (which are always interesting and thought provoking), and I definitely hope there other projects to work on together soon!!! (8/8)