Yi-Wei Yeh1, Shin-Chang Kuo2, Chun-Yen Chen3, Chih-Sung Liang4, Pei-Shen Ho5, Che-Hung Yen6, Tien-Yu Chen7, Jia-Fwu Shyu8, Fang-Jung Wan7, Ru-Band Lu9, San-Yuan Huang10. 1. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Keelung Branch, Tri-Service General Hospital, Keelung, Taiwan. 2. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Keelung Branch, Tri-Service General Hospital, Keelung, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. 3. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. 4. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 5. Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 6. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 7. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 8. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biology & Anatomy, National Defense Medical Center, Taipei, Taiwan. 9. Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 10. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: hsy@ndmctsgh.edu.tw.
Abstract
BACKGROUND: Antidepressants have variable efficacies in subjects with major depressive disorder (MDD). Nerve growth factor (NGF) has been suggested to play an important role in the pathogenesis of depressive symptoms and the response to antidepressant therapy. The aim of this study was to examine whether NGF gene polymorphisms are associated with the antidepressant therapeutic efficacy in subjects with MDD. METHODS: A naturalistic follow-up study was carried out on 557 subjects with MDD. Of the enrolled patients, 304 completed the 8-week open-label antidepressant treatment. Seven single-nucleotide polymorphisms (SNPs) of the NGF gene were genotyped. The 21-item Hamilton Depression Rating Scale was used to assess depressive severity from baseline to endpoint. Tridimensional Personality Questionnaire was used to assess baseline personality traits. Single marker and haplotype analyses were conducted. Binary logistic regression was used to calculate odds ratios of remission. Structural equation modeling was used to analyze the predicted mediation effect. RESULTS: A significant difference in genotype frequencies between remitters and non-remitters was observed in three NGF SNPs (rs12760036, rs7523654, and rs17033692). The haplotype analysis revealed that the CCC haplotype (rs2254527-rs6678788-rs12760036) was associated with a higher remission rate, while the CCA haplotype was associated with a lower remission rate. The harm avoidance psychological factor partially mediated the effect of NGF variants on antidepressant efficacy. LIMITATIONS: The selected SNPs may not cover whole NGF gene. CONCLUSIONS: NGF variants are associated with remission rates after 8-week antidepressant treatment, and harm avoidance partially mediated the effect of NGF variants on treatment outcomes.
BACKGROUND: Antidepressants have variable efficacies in subjects with major depressive disorder (MDD). Nerve growth factor (NGF) has been suggested to play an important role in the pathogenesis of depressive symptoms and the response to antidepressant therapy. The aim of this study was to examine whether NGF gene polymorphisms are associated with the antidepressant therapeutic efficacy in subjects with MDD. METHODS: A naturalistic follow-up study was carried out on 557 subjects with MDD. Of the enrolled patients, 304 completed the 8-week open-label antidepressant treatment. Seven single-nucleotide polymorphisms (SNPs) of the NGF gene were genotyped. The 21-item Hamilton Depression Rating Scale was used to assess depressive severity from baseline to endpoint. Tridimensional Personality Questionnaire was used to assess baseline personality traits. Single marker and haplotype analyses were conducted. Binary logistic regression was used to calculate odds ratios of remission. Structural equation modeling was used to analyze the predicted mediation effect. RESULTS: A significant difference in genotype frequencies between remitters and non-remitters was observed in three NGF SNPs (rs12760036, rs7523654, and rs17033692). The haplotype analysis revealed that the CCC haplotype (rs2254527-rs6678788-rs12760036) was associated with a higher remission rate, while the CCA haplotype was associated with a lower remission rate. The harm avoidance psychological factor partially mediated the effect of NGF variants on antidepressant efficacy. LIMITATIONS: The selected SNPs may not cover whole NGF gene. CONCLUSIONS:NGF variants are associated with remission rates after 8-week antidepressant treatment, and harm avoidance partially mediated the effect of NGF variants on treatment outcomes.
Authors: Anastasia Levchenko; Natalia M Vyalova; Timur Nurgaliev; Ivan V Pozhidaev; German G Simutkin; Nikolay A Bokhan; Svetlana A Ivanova Journal: Front Genet Date: 2020-08-25 Impact factor: 4.599