Possible modulatory role of ARC gene variants in mood disorders
Concetta Crisafulli 1, Marco Calabrò 1, Laura Mandelli 2, Sheng-Min Wang 3, Soo-Jung Lee 3, Changsu Han 4, Ashwin A. Patkar 5, Prakash S. Masand 6, Chi-Un Pae 3, 5, 7*, Daniel Souery 8, Julien Mendlewicz 9, Alessandro Serretti 2
1Department of Biomedical and Dental Sciences and Morphofunctional Images, University of Messina, Italy, 2Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy, 3Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea, 4Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea, 5Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA, 6Global Medical Education, New York, NY, USA, 7Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea, 8Centre Européen de Psychologie Medicale, Laboratoire de Psychologie Medicale, Universitè Libre de Bruxelles and Psy Pluriel, Belgium, 9Université Libre de Bruxelles, Belgium
Received: June 19, 2019; Accepted: July 29, 2019; Published online: July 29, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objectives: The genetic background of mood disorders is gradually emerging through the use of large multicenter samples but a detailed phenotyping is complementary in elucidating the role of modulating variants.
Methods: In the present paper we focused on the possible modulatory effects of ARC gene variants on two independent mood disorder samples of European (N=246 bipolar disorder) and Korean (N=132 bipolar disorder; N=242 major depressive disorder) ancestry.
Results: No result survived Bonferroni correction, however we evidenced promising trend toward possible association between ARC gene variants and mood disorder phenotypes. In particular, we evidenced weak correlations of ARC SNPs with depressive symptoms severity (evaluated through HDRS scores) in the MDD Korean (rs7465272) and European (rs11167152) samples. Additionally rs10110456 was found to be related to Family History, while rs7465272 was related to suicide risk in the Korean sample. Finally, rs7465272 was associated with BMI in the European sample.
Conclusion: Overall, ARC gene variants may have a partial role in modulatory effect on treatment efficacy or phenotypes of mood disorders. Further studies, on larger samples may provide a better understanding on the role of ARC gene variants in the symptom severity and treatment outcomes in patients with mood disorders.
Keywords: arc gene, depressive disorder, bipolar disorder, mood disorder, pleiotropy


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