Inflammatory Markers of Geriatric Depression Response to Tai Chi or Health Education Adjunct Interventions

Published:August 27, 2022DOI:


      • What is the primary question addressed by this study?
      • Since the role of inflammatory biomarkers to treatment response in late-life depression remains unclear, we examined changes in inflammatory markers in depressed older adults undergoing adjunct Tai Chi Chih or Health education interventions combined with a stable standard antidepressant treatment.
      • What is the main finding of this study?
      • We found that changes in cytokines/chemokines scores did not differ significantly between the two interventions. However, changes in inflammation accompany remission of depressive symptoms across both groups.
      • What is the meaning of the finding?
      • These findings may point to the therapeutic potential of targeting immune markers to treat geriatric depression.



      Underlying inflammation is associated with an increased risk of depression in older adults. In this study, we examined the role of inflammatory biomarkers in antidepressant response in depressed older adults undergoing adjunct Tai Chi Chih (TCC) or Health education interventions.


      Older adults aged 60 years and above with a diagnosis of major depression were randomized to 12 weeks of TCC versus Health and Wellness Education (HEW) as an adjunct therapy to their stable antidepressant treatment regimen. A panel of 19 cytokine/chemokines was measured at baseline and 12 weeks. Five factors were derived using factor analysis. General linear models were estimated to examine the change in factor scores and the association of these changes on depression remission rates, controlling for age, sex, and body mass index.


      Of the 170 randomized participants (TCC: n = 85 and HEW: n = 85), 55 TCC and 58 HEW completed the 3-month assessment. The groups did not differ at baseline in any measure. At follow-up, neither the changes in cytokine/chemokines scores nor the depression remission rate differed significantly between TCC and HEW. However, remitters and non-remitters differed significantly in changes in a factor composed of growth-regulated oncogene protein-alpha (GRO-alpha), epidermal growth factor (EGF), and soluble CD40 ligand (sCD40L). GRO-alpha and EGF levels (in both groups) were significantly increased in remitters compared to non-remitters.


      Changes in certain cytokines/chemokines may accompany improvement in depressive symptoms in older adults. Future studies will need to explore the role of these molecules in remission of late-life depression.

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        • Butters MA
        • Whyte EM
        • Nebes RD
        • et al.
        The nature and determinants of neuropsychological functioning in late-life depression.
        Arch Gen Psychiatry. 2004; 61: 587-595
        • Alexopoulos GS
        Mechanisms and treatment of late-life depression.
        Transl Psychiatry. 2019; 9: 188
        • Thase ME
        Achieving remission and managing relapse in depression.
        J Clin Psychiatry. 2003; 64: 3-7
        • Alexopoulos GS
        • Morimoto SS
        The inflammation hypothesis in geriatric depression.
        Int J Geriatr Psychiatry. 2011; 26: 1109-1118
        • Mac Giollabhui N
        • Ng TH
        • Ellman LM
        • et al.
        The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression.
        Mol Psychiatry. 2021; 26: 3302-3314
        • 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: 46-56
        • Franceschi C
        • Campisi J
        Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.
        J Gerontol A Biol Sci Med Sci. 2014; 69: S4-S9
        • Miller AH
        • Raison CL
        The role of inflammation in depression: from evolutionary imperative to modern treatment target.
        Nat Rev Immunol. 2016; 16: 22-34
        • Eyre HA
        • Air T
        • Pradhan A
        • et al.
        A meta-analysis of chemokines in major depression.
        Prog Neuropsychopharmacol Biol Psychiatry. 2016; 68: 1-8
        • Kohler O
        • Krogh J
        • Mors O
        • et al.
        Inflammation in depression and the potential for anti-inflammatory treatment.
        Curr Neuropharmacol. 2016; 14: 732-742
        • Lindqvist D
        • Dhabhar FS
        • James SJ
        • et al.
        Oxidative stress, inflammation and treatment response in major depression.
        Psychoneuroendocrinology. 2017; 76: 197-205
        • Sun Y
        • Drevets W
        • Turecki G
        • et al.
        The relationship between plasma serotonin and kynurenine pathway metabolite levels and the treatment response to escitalopram and desvenlafaxine.
        Brain Behav Immun. 2020; 87: 404-412
        • Wayne PM
        • Berkowitz DL
        • Litrownik DE
        • et al.
        What do we really know about the safety of tai chi?: a systematic review of adverse event reports in randomized trials.
        Arch Phys Med Rehabil. 2014; 95: 2470-2483
        • Huang Z-G
        • Feng Y-H
        • Li Y-H
        • et al.
        Systematic review and meta-analysis: Tai Chi for preventing falls in older adults.
        BMJ open. 2017; 7e013661
        • Yeh GY
        • Wang C
        • Wayne PM
        • et al.
        Tai chi exercise for patients with cardiovascular conditions and risk factors: a systematic review.
        J Cardiopulm Rehabil Prevent. 2009; 29: 152
        • Wayne PM
        • Walsh JN
        • Taylor-Piliae RE
        • et al.
        Effect of Tai Chi on cognitive performance in older adults: systematic review and meta-analysis.
        J Am Geriatr Soc. 2014; 62: 25-39
        • Weber M
        • Schnorr T
        • Morat M
        • et al.
        Effects of mind-body interventions involving meditative movements on quality of life, depressive symptoms, fear of falling and sleep quality in older adults: a systematic review with meta-analysis.
        Int J Environ Res Public Health. 2020; 17: 6556
        • Wang F
        • Lee E-KO
        • Wu T
        • et al.
        The effects of tai chi on depression, anxiety, and psychological well-being: a systematic review and meta-analysis.
        Int J Behav Med. 2014; 21: 605-617
        • Wang C
        • Collet JP
        • Lau J
        The effect of Tai Chi on health outcomes in patients with chronic conditions: a systematic review.
        Arch Intern Med. 2004; 164: 493-501
        • Irwin MR
        • Olmstead R
        Mitigating cellular inflammation in older adults: a randomized controlled trial of Tai Chi Chih.
        Am J Geriatr Psychiatry. 2012; 20: 764-772
        • Lavretsky H
        • Milillo MM
        • Kilpatrick L
        • et al.
        A randomized controlled trial of Tai Chi Chih or health education for geriatric depression.
        Am J Geriatr Psychiatry. 2022; 30: 392-403
        • Ramani T
        • Auletta CS
        • Weinstock D
        • et al.
        Cytokines: the good, the bad, and the deadly.
        Int J Toxicol. 2015; 34: 355-365
        • Paul WE
        Pleiotropy and redundancy: T cell-derived lymphokines in the immune response.
        Cell. 1989; 57: 521-524
        • Hair JF
        • Black WC
        • Babin BJ
        • et al.
        Multivariate Data Analysis.
        Pearson Education Limited, Upper Saddle River2013
        • Scheller J
        • Chalaris A
        • Schmidt-Arras D
        • et al.
        The pro- and anti-inflammatory properties of the cytokine interleukin-6.
        Biochim Biophys Acta. 2011; 1813: 878-888
        • Fanelli G
        • Benedetti F
        • Wang SM
        • et al.
        Reduced CXCL1/GRO chemokine plasma levels are a possible biomarker of elderly depression.
        J Affect Disord. 2019; 249: 410-417
        • Yi Z
        • Li Z
        • Yu S
        • et al.
        Blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder.
        PLoS One. 2012; 7: e31283
        • Pandey GN
        • Rizavi HS
        • Bhaumik R
        • et al.
        Chemokines gene expression in the prefrontal cortex of depressed suicide victims and normal control subjects.
        Brain Behav Immun. 2021; 94: 266-273
        • Brann E
        • Fransson E
        • White RA
        • et al.
        Inflammatory markers in women with postpartum depressive symptoms.
        J Neurosci Res. 2020; 98: 1309-1321
        • Chai HH
        • Fu XC
        • Ma L
        • et al.
        The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.
        FASEB J. 2019; 33: 8853-8864
        • Song AQ
        • Gao B
        • Fan JJ
        • et al.
        NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice.
        J Neuroinflammation. 2020; 17: 178
        • Lee YH
        • Kim SH
        • Kim Y
        • et al.
        Inhibitory effect of the antidepressant imipramine on NF-kappaB-dependent CXCL1 expression in TNFalpha-exposed astrocytes.
        Int Immunopharmacol. 2012; 12: 547-555
        • Santarelli L
        • Saxe M
        • Gross C
        • et al.
        Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants.
        Science. 2003; 301: 805-809
        • Hitoshi S
        • Maruta N
        • Higashi M
        • et al.
        Antidepressant drugs reverse the loss of adult neural stem cells following chronic stress.
        J Neurosci Res. 2007; 85: 3574-3585
        • Diniz BS
        • Teixeira AL
        • Machado-Vieira R
        • et al.
        Reduced serum nerve growth factor in patients with late-life depression.
        Am J Geriatr Psychiatry. 2013; 21: 493-496
        • Diniz BS
        • Reynolds 3rd, CF
        • Begley A
        • et al.
        Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study.
        J Psychiatr Res. 2014; 49: 96-101
        • Tian W
        • Zhang J
        • Zhang K
        • et al.
        A study of the functional significance of epidermal growth factor in major depressive disorder.
        Psychiatr Genet. 2012; 22: 161-167
        • Evans SJ
        • Choudary PV
        • Neal CR
        • et al.
        Dysregulation of the fibroblast growth factor system in major depression.
        Proc Natl Acad Sci U S A. 2004; 101: 15506-15511
        • Skibinska M
        • Kapelski P
        • Dmitrzak-Weglarz M
        • et al.
        Elevated epidermal growth factor (EGF) as candidate biomarker of mood disorders-longitudinal study in adolescent and young adult patients.
        J Clin Med. 2021; 10: 4064
        • Wu HE
        • Teixeira AL
        • Barroso L
        • et al.
        Epidermal growth factor and fibroblast growth factor-2 circulating levels in elderly with major depressive disorder.
        Psychiatry Res. 2019; 272: 141-143
        • Lopresti AL
        • Maes M
        • Meddens MJ
        • et al.
        Curcumin and major depression: a randomized, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change.
        Eur Neuropsychopharmacol. 2015; 25: 38-50
        • Strawbridge R
        • Arnone D
        • Danese A
        • et al.
        Inflammation and clinical response to treatment in depression: a meta-analysis.
        Eur Neuropsychopharmacol. 2015; 25: 1532-1543
        • Yang C
        • Wardenaar KJ
        • Bosker FJ
        • et al.
        Inflammatory markers and treatment outcome in treatment resistant depression: a systematic review.
        J Affect Disord. 2019; 257: 640-649