Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder
Abstract Background Antidepressant efficacy is influenced by a multitude of factors, yet predicting treatment outcomes remains challenging. This difficulty is partly due to the commonly employed dichotomous classifications of treatment response that rely on a single primary endpoint. Methods The stu...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | BMC Psychiatry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12888-025-06895-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849325930771644416 |
|---|---|
| author | Haiping Tang Yan Xia Chenjie Gao Yufan Cai Yongqi Shao Wenji Chen Yonggui Yuan Chunyu Liu Zhijun Zhang Zhi Xu |
| author_facet | Haiping Tang Yan Xia Chenjie Gao Yufan Cai Yongqi Shao Wenji Chen Yonggui Yuan Chunyu Liu Zhijun Zhang Zhi Xu |
| author_sort | Haiping Tang |
| collection | DOAJ |
| description | Abstract Background Antidepressant efficacy is influenced by a multitude of factors, yet predicting treatment outcomes remains challenging. This difficulty is partly due to the commonly employed dichotomous classifications of treatment response that rely on a single primary endpoint. Methods The study enrolled 972 patients diagnosed with depression, including both first-episode and recurrent cases. All patients received treatment with a single class of antidepressant medication over an eight-week period. Treatment response trajectories were identified through cluster analysis using normalized score change ratios from the 17-item Hamilton Rating Scale for Depression (HAMD-17) at baseline and weeks 2, 4, 6, and 8. The impact of psychosocial factors—including childhood trauma experience, social support, and family environment—on these response patterns was evaluated using ANOVA and Tukey’s HSD tests. Additionally, targeted exome sequencing was conducted to perform rare-variant burden and enrichment analyses to investigate genetic influences on antidepressant response. Results Three patterns of antidepressant treatment response were identified: gradual response (C1 cluster), early response (C2 cluster), and fluctuating response (C3 cluster). Notably, patients in the C3 cluster exhibited higher levels of suicidal ideation, alexithymia, and anhedonia after the treatment period, along with the highest baseline levels of family control (a subscale of the family environment). Our rare-variant analysis revealed genes associated with response efficiency between C1 and C2 clusters to be significantly enriched in the neurotrophin signaling pathway (odds ratio = 23.94; p-adjusted = 6.96e-05). In addition, genes linked to response volatility between C1 and C3 clusters were enriched in the regulation of inflammatory mediators of transient receptor potential (TRP) channels (odds ratio = 31.5; p-adjusted = 1.83e-07). Conclusions Our findings suggest that patients exhibiting a fluctuating response to antidepressant treatment may endure more severe clinical symptoms throughout the treatment course. The involvement of the neurotrophin signaling pathway and TRP channels in these response patterns highlights their potential as novel targets for therapeutic intervention in depression. This underscores the importance of personalized treatment strategies that consider the underlying genetic and psychological factors influencing antidepressant efficacy. |
| format | Article |
| id | doaj-art-9c4e0a7da3324a3fbb9eed72bde1c1e0 |
| institution | Kabale University |
| issn | 1471-244X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Psychiatry |
| spelling | doaj-art-9c4e0a7da3324a3fbb9eed72bde1c1e02025-08-20T03:48:18ZengBMCBMC Psychiatry1471-244X2025-05-0125111410.1186/s12888-025-06895-0Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorderHaiping Tang0Yan Xia1Chenjie Gao2Yufan Cai3Yongqi Shao4Wenji Chen5Yonggui Yuan6Chunyu Liu7Zhijun Zhang8Zhi Xu9Department of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast UniversityDepartment of Molecular Biophysics and Biochemistry, Yale UniversityDepartment of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast UniversityDepartment of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast UniversityDepartment of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast UniversityDepartment of General Practice, School of Medicine, Zhongda Hospital, Southeast UniversityDepartment of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast UniversityCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South UniversityDepartment of Neurology, Affiliated Zhongda Hospital, Southeast UniversityDepartment of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast UniversityAbstract Background Antidepressant efficacy is influenced by a multitude of factors, yet predicting treatment outcomes remains challenging. This difficulty is partly due to the commonly employed dichotomous classifications of treatment response that rely on a single primary endpoint. Methods The study enrolled 972 patients diagnosed with depression, including both first-episode and recurrent cases. All patients received treatment with a single class of antidepressant medication over an eight-week period. Treatment response trajectories were identified through cluster analysis using normalized score change ratios from the 17-item Hamilton Rating Scale for Depression (HAMD-17) at baseline and weeks 2, 4, 6, and 8. The impact of psychosocial factors—including childhood trauma experience, social support, and family environment—on these response patterns was evaluated using ANOVA and Tukey’s HSD tests. Additionally, targeted exome sequencing was conducted to perform rare-variant burden and enrichment analyses to investigate genetic influences on antidepressant response. Results Three patterns of antidepressant treatment response were identified: gradual response (C1 cluster), early response (C2 cluster), and fluctuating response (C3 cluster). Notably, patients in the C3 cluster exhibited higher levels of suicidal ideation, alexithymia, and anhedonia after the treatment period, along with the highest baseline levels of family control (a subscale of the family environment). Our rare-variant analysis revealed genes associated with response efficiency between C1 and C2 clusters to be significantly enriched in the neurotrophin signaling pathway (odds ratio = 23.94; p-adjusted = 6.96e-05). In addition, genes linked to response volatility between C1 and C3 clusters were enriched in the regulation of inflammatory mediators of transient receptor potential (TRP) channels (odds ratio = 31.5; p-adjusted = 1.83e-07). Conclusions Our findings suggest that patients exhibiting a fluctuating response to antidepressant treatment may endure more severe clinical symptoms throughout the treatment course. The involvement of the neurotrophin signaling pathway and TRP channels in these response patterns highlights their potential as novel targets for therapeutic intervention in depression. This underscores the importance of personalized treatment strategies that consider the underlying genetic and psychological factors influencing antidepressant efficacy.https://doi.org/10.1186/s12888-025-06895-0Antidepressant efficacyTarget exome sequencingRare variantsResponse trajectoriesGenetic factorsPsychosocial factors |
| spellingShingle | Haiping Tang Yan Xia Chenjie Gao Yufan Cai Yongqi Shao Wenji Chen Yonggui Yuan Chunyu Liu Zhijun Zhang Zhi Xu Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder BMC Psychiatry Antidepressant efficacy Target exome sequencing Rare variants Response trajectories Genetic factors Psychosocial factors |
| title | Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder |
| title_full | Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder |
| title_fullStr | Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder |
| title_full_unstemmed | Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder |
| title_short | Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder |
| title_sort | association of psychosocial factors and biological pathways identified from rare variant analysis with longitudinal trajectories of treatment response in major depressive disorder |
| topic | Antidepressant efficacy Target exome sequencing Rare variants Response trajectories Genetic factors Psychosocial factors |
| url | https://doi.org/10.1186/s12888-025-06895-0 |
| work_keys_str_mv | AT haipingtang associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT yanxia associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT chenjiegao associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT yufancai associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT yongqishao associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT wenjichen associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT yongguiyuan associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT chunyuliu associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT zhijunzhang associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder AT zhixu associationofpsychosocialfactorsandbiologicalpathwaysidentifiedfromrarevariantanalysiswithlongitudinaltrajectoriesoftreatmentresponseinmajordepressivedisorder |