Thread by @nilskappelmann

Excited to share our publication on #inflammation, #metabolic dysregulation, & #depression symptoms now out @JAMAPsych!

This is work by @Binder_Lab, Janine Arloth, @mgeorgakis1, @and_Ramses_II, Symen Ligthart, & @golam_khandaker.

Tweetorial below

jamanetwork.com/journals/jamap…

https://twitter.com/JAMAPsych/status/1318556867409420290

In this project we studied symptom heterogeneity in #depression, which is highly prevalent and may hamper ongoing research efforts in depression. @caina89, @karmelchoi, & @EikoFried have recently conducted an excellent review on the genetic side of this:
academic.oup.com/hmg/article/29…

In our study, we focused on the association of #inflammation w/ specific depressive symptoms, which was previously largely described in cross-sectional studies, but also some longitudinal & polygenic risk score work.

Please look up research by @PsychRes, @Ygoes2B_more, @LamersFemke, @mmjokela, @dp_moriarity, @kohler_ole, & @golam_khandaker who have particularly contributed to this line of research (& probably many others that I am forgetting right now).

In our study, we wanted to investigate genetic correlations/ co-heritability of #inflammation & metabolic dysregulation w/ depressive symptoms and we found evidence for small but robust co-heritability of these traits across depressive symptoms.

Interestingly, estimates of CRP (indexing inflammation) & BMI (indexing metabolic dysregulation) w/ depressive symptoms were highly similar, pointing towards the well-described immuno-metabolic depression
biologicalpsychiatryjournal.com/article/S0006-…

Next, we used Mendelian Randomisation (MR) to evaluate a potential causal association of CRP & IL-6 (indexing inflammation), BMI (indexing metabolic dysregulation), & depressive symptoms.

See this paper describing the MR approach:
onlinelibrary.wiley.com/doi/10.1002/si…

Contrary to genetic correlation results, we found no MR associations of CRP w/ depressive symptoms. However, we found associations of IL-6 w/ suicidality and of BMI w/ anhedonia, fatigue, changes in appetite and feelings of inadequacy.

These findings highlight a potential causal role of IL-6 signalling on suicidality, which could have important clinical implications as pharmacological approaches for IL-6 are available (e.g., for rheumatoid arthritis) or under development.

@golam_khandaker is currently running an RCT testing #tocilizumab for depression (a monoclonal antibody against the IL-6 receptor).

Findings from this RCT and others will help triangulate evidence for a causal association of IL-6 w/ suicidality

bmjopen.bmj.com/content/8/9/e0…

Combining results of CRP & IL-6 w/ BMI also shows interesting specificity of symptom associations that may highlight a unique immuno-metabolic symptom profile in depression.

Expression of these symptoms could help stratify patients into future RCTs.

Please check out the paper if you're interested in further details & discussion, which is published #OpenAccess:

jamanetwork.com/journals/jamap…

As requested, I'm tagging @mariabloec here.😊

Premonition that I would be forgetting important people, so now also tagging @ChiaraFabbri12. Really appreciated the work you presented on this at #WCPG2020 using polygenic risk scores!