Daniel Baksa1,2, Xenia Gonda3,4,5, Nora Eszlari2,3, Peter Petschner2,5, Gyorgy Bagdy2,3,5,, Gabriella Juhasz1,2,5,6
1 SE-NAP2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary
2 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
3 NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary
4 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest
5 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
6 Neuroscience and Psychiatry Unit, Division of Neuroscience & Experimental Psychology, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, United Kingdom
Introduction: According to previous studies both maladaptive stress response and circadian factors might have a role in migraine. Although, effects of circadian genes on common migraine have not been tested yet. CLOCK gene works as a transcriptional activator in the main circadian mechanism and its tagSNP rs10462028 previously associated with bipolar disorder, a comorbid disease of migraine.
Aims: Our goal was to the test the main effect of rs10462028 of CLOCK and its interaction with different stress factors on migraine.
Method: 2157 subjects recruited from Manchester and Budapest completed the ID-Migraine questionnaire to capture migraine. Additional stress factors were: childhood maltreatment (shortened version of Childhood Trauma Questionnaire), recent negative life events (List of Threatening Experiences) and financial difficulties (from our background questionnaire). Logistic regression models were used to test the main effect of rs10462028 and the SNP x stress factors interaction effects on migraine in the total population and both subsamples. All models (additive, dominant, recessive) were adjusted for gender, age, population, and possible confounding effects of lifetime bipolar disorder and depression (derived from our background questionnaire) were also tested.
Results: Rs10462028 showed no main genetic effect on migraine. Among stress factors, only financial difficulties interacted significantly with rs10462028 (p=0.006 in recessive model) on migraine. This latter result was replicated in both population subsamples, and survived correction for lifetime bipolar disorder and depression, although only a trend effect was reached after Bonferroni-correction.
Conclusion: Our exploratory study suggests the variations in the CLOCK gene might alter risk of migraine in the presence of financial difficulties, a chronic stress factor.
Doctoral School: Mental Health Sciences
Supervisor: Dr. Gabriella Juhász
The study was supported by the Hungarian Brain Research Program (KTIA_13_NAP-A-II/14, 2017-1.2.1-NKP-2017-00002); by the National Development Agency (KTIA_NAP_13-1-2013-0001); by the Sixth Framework Program of the European Union, NewMood (Grant No. LSHM-CT-2004-503474); by the Hungarian Academy of Sciences, Semmelweis University and the Hungarian Brain Research Program (MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Grant KTIA_NAP_13-2-2015-0001); by the National Institute for Health Research Manchester Biomedical Research Centre; by the Hungarian Academy of Sciences (MTA-SE Neuropsychopharmacology and Neurochemistry Research Group) and New National Excellence Program of The Ministry of Human Capacities (UNKP-16-3, UNKP-17-3-III-SE-2, UNKP-17-4-I-SE-8). XG is a recipient of the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. The sponsors had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.