Abstract
The serotonin 1A receptor gene (HTR1A) has been associated with mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Therefore, we conducted a systematic review and meta-analysis between rs6295 (C-1019G) as well as rs878567 in HTR1A and MDs. Searching PubMed through May 2012, 15 studies, including our own, previously unpublished association study (135 MDD patients and 107 healthy controls), met inclusion criteria for the meta-analysis of rs6295 (4,297 MDs patients and 5,435 controls). Five association studies met criteria for the meta-analysis of rs878567 (2041MDs patients and 2,734 controls). rs6295 was associated with combined MDs (P allele model = 0.007 and P recessive model = 0.01). When divided by diagnostic subgroup (MDD = 3,119 patients and 4,380 controls or BP = 1,170 patients and 2,252 controls), rs6295 was associated with each MDs separately (MDD: P allele model = 0.006, P recessive model = 0.01; BP: P dominant model = 0.003). Likewise, rs878567 was associated with combined MDs (2,041 patients and 2,734 controls (P allele model = 0.0002, P dominant model = 0.0008, and P recessive model = 0.01). When divided by diagnostic subgroup (MDD = 1,013 patients and 1,728 controls or BP = 1,051 patients and 2,099 controls), rs878567 was associated with MDD (P allele model = 0.0007 and P dominant model = 0.01), while only one BP study had such data, precluding a meta-analysis. All of these significances survived correction for multiple comparisons. Results from this expanded meta-analysis, which included our own new study, suggest that rs6295 (C-1019G) and rs878567 in HTR1A are related to the pathophysiology of MDs, with overlap between MDD and BP. Findings provide additional clues to the underlying biology and treatment targets in MDs.
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Acknowledgments
We thank Dr. David A. Katz, Dr. Raffaella Calati, and Dr. John M. Hettema for providing genotype information for the study. We thank Ms. M. Miyata and Ms. S. Ishihara for their technical support. This work was supported in part by research grants from the Japan Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation). Dr. Kishi is a postdoctoral fellow for research abroad and is additionally supported by the Japan Research Foundation for Clinical Pharmacology and the Ministry of Education. This work was supported in part by research grants from the Smoking Research Foundation, Japan. Research Foundation for Clinical Pharmacology and the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Japan Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation).
Financial Disclosures
Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Actelion, AstraZeneca, Biotis, Bristol-Myers Squibb, Cephalon, Eli Lilly, IntraCellular Therapies; Ortho-McNeill/Janssen/J&J, Merck, Novartis, Otsuka, Pfizer, and Sepracor/Sunovion. He has received grant support from the Feinstein Institute for Medical Research, the National Institute of Mental Health (NIMH), and the National Alliance for Research in Schizophrenia and Depression (NARSAD), BMS, Otsuka and Ortho-McNeill/Janssen/J&J. Dr. Kane has been a consultant and/or advisor to or has received honoraria from Alkermes, Amgen, Astra-Zeneca, BMS, Boehringer Ingelheim, Cephalon, Eli Lilly, Esai, Intracellular Therapies, Janssen, Johnson and Johnson, Lundbeck, Merck, Novartis, Otsuka, Pfizer, Pierre Fabre, Proteus, Roche, Sunovion, Targacept. He is a shareholder of MedAvante and has received grant support from the NIMH.
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Kishi, T., Yoshimura, R., Fukuo, Y. et al. The serotonin 1A receptor gene confer susceptibility to mood disorders: results from an extended meta-analysis of patients with major depression and bipolar disorder. Eur Arch Psychiatry Clin Neurosci 263, 105–118 (2013). https://doi.org/10.1007/s00406-012-0337-4
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DOI: https://doi.org/10.1007/s00406-012-0337-4