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Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene

Annerbrink, Kristinaa; Westberg, Larsa; Olsson, Mariec; Andersch, Svenb; Sjödin, Ingemare; Holm, Görand; Allgulander, Christerf; Eriksson, Eliasa

doi: 10.1097/YPG.0b013e328341a3db
Original Articles

Background Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now.

Methods We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls.

Results Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients.

Conclusion Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.

Departments of aPharmacology

bPsychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg

cDepartment of Pharmacy, Apoteket AB

dDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg

eDepartment of Clinical and Experimental Medicine, Psychiatry, Linköping University

fDepartment of Clinical Neuroscience, Karolinska Institutet, Section of Psychiatry, Stockholm, Sweden

Correspondence to Dr Kristina Annerbrink, MD, PhD, Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, PO Box 431, SE 405 30 Gothenberg, Sweden Tel: +46 31 7733448; fax: +46 31 786 3065; e-mail:

Received March 30, 2010

Accepted August 9, 2010

© 2011 Lippincott Williams & Wilkins, Inc.