2012 Liou-Convergent evidence from mouse and human studies suggests the involvement of zinc finger protein 326 gene in antidepressant treatment response.pdf
[en] [en] OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment.
METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498).
RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028).
CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response.
Disciplines :
Genetics & genetic processes
Author, co-author :
Liou, Ying-Jay; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
Chen, Chien-Hsiun; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan ; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
Cheng, Chih-Ya; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Chen, Shiow-Yi; Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan
Nian, Fang-Shin ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
Tsai, Shih-Jen; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
Hong, Chen-Jee; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan ; Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan ; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
Language :
English
Title :
Convergent evidence from mouse and human studies suggests the involvement of zinc finger protein 326 gene in antidepressant treatment response.
We would like to thank the National Genotyping Center of the National Research Program for Genomic Medicine, launched by the National Science Council, and Dr. Jer-Yuan Wu of Academia Sinica, Taiwan, for support in the genotyping of samples. The authors report no biomedical financial interests or potential conflicts of interest. No assistance was received in the writing of this manuscript.
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