Research Submission No Influence of 5-HTTLPR Gene Polymorphism on Migraine Symptomatology, Comorbid Depression, and Chronification Thomas Wieser, MD; Kathrin Dresler, MD; Stefan Evers, MD, PhD; Charly Gaul, MD; Dorothea König; Daniela Hölzl; Klaus Berger, MD; Dale Nyholt, PhD; Thomas Deufel, MD Background.—The serotonergic system is thought to play an important role for mediating susceptibility to migraine and depression, which is frequently found comorbid in migraine. The functional polymorphism in the serotonin transporter gene linked polymorphic region (5-HTTLPR/SLC6A4) was previously associated with attack frequency and, thus, possibly with chronification. Objective.—We hypothesized that patients with the “s” allele have higher attack frequency and, paralleling results in depression research, higher scores of depression. Methods.—Genetic analysis of the SLC6A4 44 bp insertion/deletion polymorphism (5-HTTLPR) was performed in 293 patients with migraine with and without aura. Self-rating questionnaires were used for assessment of depression. Results.—Multinomial logistic regression analysis found no evidence for association of the 5-HTTLPR polymorphism with either depression or migraine attack frequency. Conclusion.—We were not able to demonstrate any influence of the serotonin transporter 5-HTTLPR polymorphism on migraine phenomenology (attack frequency or comorbid depression), thereby excluding this variant to be a common genetic denominator for chronic migraine and depression. Key words: migraine, serotonin transporter, polymorphism, depression, chronification Abbreviations: 5-HT serotonin, 5-HTTLPR serotonin transporter linked polymorphic region, ICHD-II International Classi- fication of Headache Disorders Version II, MA migraine with aura, MO migraine without aura, CM chronic migraine, TTH tension-type headache, DMKG Deutsche Migräne und Kopfschmerzgesellschaft (German Headache Society), BDI Beck Depression Inventory, CES-D Center for Epidemiologic Studies Depression Scale (Headache 2010;50:420-430) From Neurologie, Krankenhaus Göttlicher Heiland, Vienna, Austria (T. Weiser); Abteilung für Allgemeine Anästhesie und Schmerztherapie, Medizinische Universität Wien, Vienna, Austria (T. Weiser); Friedrich-Schiller-Universität Jena, Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Jena, Germany (K. Dresler; T. Deufel); Klinik für Neurologie, Universitätsklinikum Münster, Münster, Germany (S. Evers); Klinik für Neurologie, Martin-Luther-Universität Halle/ Wittenberg, Halle/S., Germany (C. Gaul); Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia (D. Nyholt); Institut für Klinische, Biologische und Differentielle Psychologie, Fakultät für Psychologie, Universität Wien, Vienna, Austria (D. König); Medizinische Statistik und Informatik, Medizinische Universität Wien, Allgemeines Krankenhaus, Vienna, Austria (D. Hölzl); Institut für Epidemiologie und Sozialmedizin, Universitätsklinikum Münster, Münster, Germany (K. Berger). Address all correspondence to T. Wieser, KH Göttlicher Heiland, Dornbacherstr. 20-28, 1170 Vienna, Austria. Accepted for publication February 4, 2009. Conflict of Interest: None ISSN 0017-8748 doi: 10.1111/j.1526-4610.2009.01428.x Published by Wiley Periodicals, Inc. Headache © 2009 the Authors Journal compilation © 2009 American Headache Society 420