Opposite effects of CGRP-related genes on migraine and depression

Title : Opposite effects of CGRP-related genes on migraine and depression

Abstract:

Introduction: Anti-calcitonin gene-related peptide (CGRP) migraine medications may also reduce symptoms of depression, a comorbid disease of migraine with overlapping genetic background. Currently, we do not understand the biological background of this phenomenon. Here, we aimed to test the effect of polygenic risk score (PRS) of a CGRP-related gene set on migraine and depression.

Methods: A sample of the UK Biobank database (Application no. 71718) was used (N=134,197) in our cross-sectional study. Migraine and depression status were based on ICD-10 codes (G43 and F32/F33, respectively), and we also used a questionnaire-based current depression score. The CGRP gene set was defined according to the Pathway Commons database (N_genes=29). PRS was calculated with LDpred2. To test the predictive value of the PRS, we performed linear regressions with R (4.1.2) separately on migraine, depression, and current depression score.

Results: The CGRP gene set PRS showed a significant risk effect on migraine (beta=0.4981, p=0.0067) but not on depression diagnosis, although a significant protective effect on current depression score (beta=-0.2466, p=0.0319) was detected. 

Conclusion: A CGRP-related gene set showed a risk effect on migraine, but a protective effect on current depression symptoms that might suggest a better mental health state among migraine patients with higher CGRP-related genetic risk.

Funding: 2017-1.2.1-NKP-2017-00002; NAP2022-I-4/2022; TKP2021-EGA-25; 2019-2.1.7-ERA-NET-2020-00005, ERAPERMED2019-108; K 143391; ÚNKP-23-4-II-SE-2

Audience Take Away Notes:

• The presenter will provide current knowledge on the effect of anti-CGRP medications on depression symptoms of migraine patients.
• The first possible explanation of this phenomenon from a genetic standpoint, specifically the effect of a CGRP-related gene set on migraine and depression will be presented.
• Our results may suggest CGRP-related targets for future pharmacogenetic studies.
• In the long term, our results might be useful in identifying migraine subgroups whose comorbid depression symptoms can benefit from anti-CGRP treatment.

Biography:

Dr. Baksa studied psychology at the Eötvös Loránd University, Hungary and graduated as MA in 2013. In 2016, he joined the research group of Gabriella Juhász, MD, D.Sc at the Department of Pharmacodynamics, Semmelweis University, Hungary, and received his PhD degree in 2023 at the same institution. Currently, he is involved in two research projects led by Gabriella Juhász. He became an assistant lecturer at the Department of Personality and Clinical Psychology, Pazmany Peter Catholic University, Hungary. He has published 26 research articles in the fields of genetics and fMRI, covering topics of migraine, circadian rhythm, and depression.