A trajectories analysis of baseline biomarkers and post-traumatic depression symptoms based on a longitudinal cohort_Chinese Journal of Evidence-Based Medicine

Authors：

LIN Zihan ^1,2 , ZENG Yu ^1,2 , XU Yueyao ^1,2 , WANG Guanglin ³ , LI Kang ^1,2 ,  ZENG Yu ^1,2 ,  SONG Huan ^1,2

1. West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Med-X Center for Informatics, Sichuan University, Chengdu 610041, P. R. China;
3. Trauma Medical Center, Department of Orthopedics Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding?author：

ZENG Yu, Email: zengyu123@wchscu.cn; SONG Huan, Email: songhuan@wchscu.cn

Keywords：

Depression; Trauma; Biomarker; Trajectory analysis; Cohort study

DOI：

10.7507/1672-2531.202601022

Video：

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Objective This longitudinal cohort study aimed to identify the association between baseline physiological characteristics and the risk of post-trauma depressive symptoms, characterize the heterogeneous developmental trajectories of these symptoms, and explore differences in baseline biomarkers across these trajectory groups to provide evidence for early clinical intervention. Methods A total of 4 709 trauma patients were recruited from the China Severe Trauma Cohort (CSTC) between March 2020 and July 2025. 17 baseline biomarkers and 6 composite inflammatory index were measured, and depressive symptoms were assessed using the PHQ-9 at 1, 3, 6, and 12 months post-admission. Multivariate-adjusted Poisson regression was used to evaluate the predictive value of baseline indicators for post-trauma depressive symptoms, and Latent Class Mixed Models (LCMM) were employed to identify depression symptom developmental trajectories. Results Elevated baseline systemic inflammation (higher leukocytes, NLR, SII, and CAR) and compromised nutritional/metabolic status (lower RBC count and albumin) significantly increased the risk of post-trauma depressive symptoms throughout the follow-up period. Trajectory analysis identified two distinct classes: "Consistently Low" and "Persistently Elevated" symptoms. Individuals in the "Persistently Elevated" group were significantly characterized by baseline profiles of low lymphocytes, albumin, red blood cells, and hematocrit. Additionally, biomarker effects exhibited some heterogeneity across gender. Conclusion Systemic inflammation activation (high white blood cell count, NLR, SII and CAR) and biological disorders driven by impaired red blood cell or nutritional status (low red blood cell count, MCHC and albumin) are significant predictors of the occurrence and persistent evolution of depressive symptoms. Baseline innate immune activation and insufficient nutritional reserves serve as early biological predictors driving the onset and chronicity of post-trauma depressive symptoms. Integrating routine hematological indicators facilitates clinical risk stratification and precision prediction of symptom trajectories.

Citation： LIN Zihan, ZENG Yu, XU Yueyao, WANG Guanglin, LI Kang, ZENG Yu, SONG Huan. A trajectories analysis of baseline biomarkers and post-traumatic depression symptoms based on a longitudinal cohort. Chinese Journal of Evidence-Based Medicine, 2026, 26(7): 799-813. doi: 10.7507/1672-2531.202601022 Copy

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4.	Magin ZE, Park CL, Burke JD, et al. Perceived control and inflammation: mediating and moderating effects in the relationship between cumulative trauma and depression. Psychosom Med, 2024, 86(3): 192-201.
5.	Li Y, Zhang L, Qin B, et al. Childhood trauma, inflammatory signatures, and fluoxetine response in adolescent depression: a cross-sectional and longitudinal study. J Affect Disord, 2026, 398: 121036.
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16.	Cheng Y, Wang Y, Wang X, et al. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depression: an updated systematic review and meta-analysis. Front Psychiatry, 2022, 13: 893097.
17.	Mazza MG, De Lorenzo R, Conte C, et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun, 2020, 89: 594-600.
18.	K?hler CA, Freitas TH, Maes M, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand, 2017, 135(5): 373-387.
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28.	Wen X, Wang F, Tang T, et al. Sex-specific association of peripheral blood cell indices and inflammatory markers with depressive symptoms in early adolescence. J Affect Disord, 2024, 362: 134-144.
29.	Shafiee M, Tayefi M, Hassanian SM, et al. Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: a sex-stratified analysis in a population-based study. Psychoneuroendocrinology, 2017, 84: 101-108.
30.	Marx W, Lane M, Hockey M, et al. Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry, 2021, 26(1): 134-150.
31.	Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron, 2020, 107(2): 234-256.
32.	Dantzer R, O'Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci, 2008, 9(1): 46-56.
33.	Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry, 2009, 65(9): 732-741.
34.	Haroon E, Miller AH, Sanacora G. Inflammation, glutamate, and glia: a trio of trouble in mood disorders. Neuropsychopharmacology, 2017, 42(1): 193-215.
35.	Jin H, Li M, Jeong E, et al. A body-brain circuit that regulates body inflammatory responses. Nature, 2024, 630(8017): 695-703.
36.	Borchers A, Pieler T. Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs. Genes (Basel), 2010, 1(3): 413-426.
37.	Al-Marwani S, Batieha A, Khader Y, et al. Association between albumin and depression: a population-based study. BMC Psychiatry, 2023, 23(1): 780.
38.	Hillmer L, Erhardt EB, Caprihan A, et al. Blood-brain barrier disruption measured by albumin index correlates with inflammatory fluid biomarkers. J Cereb Blood Flow Metab, 2023, 43(5): 712-721.
39.	Al-Tarrah K, Moiemen N, Lord JM. The influence of sex steroid hormones on the response to trauma and burn injury. Burns Trauma, 2017, 5: 29.
40.	Lee YJ, Kim HB. Association between anaemia and adult depression: a systematic review and meta-analysis of observational studies. J Epidemiol Community Health, 2020, 74(7): 565-572.

1. WHO. Depressive disorder (depression) 2025. 2025.
2. Hammen C. Risk factors for depression: an autobiographical review. Annu Rev Clin Psychol, 2018, 14: 1-28.
3. Cai Y, Huang G, Ren M, et al. Identification of preventive biomarkers associated with circadian rhythms in traumatic brain injury-mediated depression: expression of SERPINE1 protein and bioinformatics analysis. Int J Biol Macromol, 2025, 310(Pt 1): 143229.
4. Magin ZE, Park CL, Burke JD, et al. Perceived control and inflammation: mediating and moderating effects in the relationship between cumulative trauma and depression. Psychosom Med, 2024, 86(3): 192-201.
5. Li Y, Zhang L, Qin B, et al. Childhood trauma, inflammatory signatures, and fluoxetine response in adolescent depression: a cross-sectional and longitudinal study. J Affect Disord, 2026, 398: 121036.
6. Lee CH, Giuliani F. The role of inflammation in depression and fatigue. Front Immunol, 2019, 10: 1696.
7. Harsanyi S, Kupcova I, Danisovic L, et al. Selected biomarkers of depression: what are the effects of cytokines and inflammation. Int J Mol Sci, 2022, 24(1): 578.
8. Kiecolt-Glaser JK, Derry HM, Fagundes CP. Inflammation: depression fans the flames and feasts on the heat. Am J Psychiatry, 2015, 172(11): 1075-1091.
9. Osimo EF, Pillinger T, Rodriguez IM, et al. Inflammatory markers in depression: a meta-analysis of mean differences and variability in 5 166 patients and 5 083 controls. Brain Behav Immun, 2020, 87: 901-909.
10. Disner SG, Beevers CG, Haigh EA, et al. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci, 2011, 12(8): 467-477.
11. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol, 2016, 16(1): 22-34.
12. Zeng Y, Chourpiliadis C, Hammar N, et al. Inflammatory biomarkers and risk of psychiatric disorders. JAMA Psychiatry, 2024, 81(11): 1118-1129.
13. Brydges CR, Bhattacharyya S, Dehkordi SM, et al. Metabolomic and inflammatory signatures of symptom dimensions in major depression. Brain Behav Immun, 2022, 102: 42-52.
14. Ng A, Tam WW, Zhang MW, et al. IL-1β, IL-6, TNF- α and CRP in elderly patients with depression or Alzheimer's disease: systematic review and meta-analysis. Sci Rep, 2018, 8(1): 12050.
15. Uher R, Tansey KE, Dew T, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014, 171(12): 1278-1286.
16. Cheng Y, Wang Y, Wang X, et al. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depression: an updated systematic review and meta-analysis. Front Psychiatry, 2022, 13: 893097.
17. Mazza MG, De Lorenzo R, Conte C, et al. Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors. Brain Behav Immun, 2020, 89: 594-600.
18. K?hler CA, Freitas TH, Maes M, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand, 2017, 135(5): 373-387.
19. Yang Y, Yuan M, Zeng Y, et al. Cohort profile: the china severe trauma cohort (CSTC). J Epidemiol, 2024, 34(1): 41-50.
20. Zhang W, Wang C, Fu T, et al. CD4?+?T lymphocyte and cytokine profiles in depressive disorders. BMC Psychiatry, 2025, 25(1): 911.
21. Yin J, Gong R, Zhang M, et al. Associations between sleep disturbance, inflammatory markers and depressive symptoms: mediation analyses in a large NHANES community sample. Prog Neuropsychopharmacol Biol Psychiatry, 2023, 126: 110786.
22. Lin J, Yang X, Wu Z, et al. C-reactive protein-to-albumin ratio is associated with increased depression: An exploratory cross-sectional analysis. J Affect Disord, 2025, 382: 131-138.
23. Jarkas DA, Villeneuve AH, Daneshmend AZB, et al. Sex differences in the inflammation-depression link: a systematic review and meta-analysis. Brain Behav Immun, 2024, 121: 257-268.
24. Hoffmann JP, Liu JA, Seddu K, et al. Sex hormone signaling and regulation of immune function. Immunity, 2023, 56(11): 2472-2491.
25. Zheng Y, Yin K, Li L, et al. Association between immune-inflammation-based prognostic index and depression: an exploratory cross-sectional analysis of NHANES data. J Affect Disord, 2024, 362: 75-85.
26. Meng F, Yan X, Qi J, et al. Association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio with depression: a cross-sectional analysis of the NHANES data. J Affect Disord, 2022, 315: 168-173.
27. Lengvenyte A, Strumila R, Belzeaux R, et al. Associations of white blood cell and platelet counts with specific depressive symptom dimensions in patients with bipolar disorder: analysis of data from the FACE-BD cohort. Brain Behav Immun, 2023, 108: 176-187.
28. Wen X, Wang F, Tang T, et al. Sex-specific association of peripheral blood cell indices and inflammatory markers with depressive symptoms in early adolescence. J Affect Disord, 2024, 362: 134-144.
29. Shafiee M, Tayefi M, Hassanian SM, et al. Depression and anxiety symptoms are associated with white blood cell count and red cell distribution width: a sex-stratified analysis in a population-based study. Psychoneuroendocrinology, 2017, 84: 101-108.
30. Marx W, Lane M, Hockey M, et al. Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry, 2021, 26(1): 134-150.
31. Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron, 2020, 107(2): 234-256.
32. Dantzer R, O'Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci, 2008, 9(1): 46-56.
33. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry, 2009, 65(9): 732-741.
34. Haroon E, Miller AH, Sanacora G. Inflammation, glutamate, and glia: a trio of trouble in mood disorders. Neuropsychopharmacology, 2017, 42(1): 193-215.
35. Jin H, Li M, Jeong E, et al. A body-brain circuit that regulates body inflammatory responses. Nature, 2024, 630(8017): 695-703.
36. Borchers A, Pieler T. Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs. Genes (Basel), 2010, 1(3): 413-426.
37. Al-Marwani S, Batieha A, Khader Y, et al. Association between albumin and depression: a population-based study. BMC Psychiatry, 2023, 23(1): 780.
38. Hillmer L, Erhardt EB, Caprihan A, et al. Blood-brain barrier disruption measured by albumin index correlates with inflammatory fluid biomarkers. J Cereb Blood Flow Metab, 2023, 43(5): 712-721.
39. Al-Tarrah K, Moiemen N, Lord JM. The influence of sex steroid hormones on the response to trauma and burn injury. Burns Trauma, 2017, 5: 29.
40. Lee YJ, Kim HB. Association between anaemia and adult depression: a systematic review and meta-analysis of observational studies. J Epidemiol Community Health, 2020, 74(7): 565-572.

Chinese Journal of Evidence-Based Medicine

A trajectories analysis of baseline biomarkers and post-traumatic depression symptoms based on a longitudinal cohort

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