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Addressing the tuberculosis–depression syndemic to end the tuberculosis epidemic
Open accessAbstract
Tuberculosis (TB) and depression act synergistically via social, behavioral, and biological mechanisms to magnify the burden of disease. Clinical depression is a common, under-recognized, yet treatable condition that, if comorbid with TB, is associated with increased morbidity, mortality, community TB transmission, and drug resistance. Depression may increase risk of TB reactivation, contribute to disease progression, and/or inhibit the physiological response to anti-tuberculosis treatment because of poverty, undernutrition, immunosuppression, and/or negative coping behaviors, including substance abuse. Tuberculous infection and/or disease reactivation may precipitate depression as a result of the inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis. Clinical depression may also be triggered by TB-related stigma, exacerbating other underlying social vulnerabilities, and/or may be attributed to the side effects of anti-tuberculosis treatment. Depression may negatively impact health behaviors such as diet, health care seeking, medication adherence, and/or treatment completion, posing a significant challenge for global TB elimination. As several of the core symptoms of TB and depression overlap, depression often goes unrecognized in individuals with active TB, or is dismissed as a normative reaction to situational stress. We used evidence to reframe TB and depression comorbidity as the 'TB-depression syndemic', and identified critical research gaps to further elucidate the underlying mechanisms. The World Health Organization's Global End TB Strategy calls for integrated patient-centered care and prevention linked to social protection and innovative research. It will require multidisciplinary approaches that consider conditions such as TB and depression together, rather than as separate problems and diseases, to end the global TB epidemic.
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“Among these, the psychological burden associated with TB has emerged as a particularly important determinant of treatment engagement and outcomes, yet it is still insufficiently addressed in routine TB care [6].”
From Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches. (2026) · cites this paper as [6]
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“It may contribute to depression and anxiety through internalized shame and experiences of discrimination; delay help-seeking because of fear of disclosure; interfere with adherence by making treatment-taking visible; and intensify social isolation through both self-protective withdrawal and rejection by others [6,27,35].”
From Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches. (2026) · cites this paper as [6]
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“Conversely, TB may precipitate depression, as a result of altered inflammatory responses and/or dysregulation of the hypothalamic-pituitary-adrenal axis, or the side effects of ATT.9”
From Pharmacological or non-pharmacological interventions for treatment of common mental disorders associated with Tuberculosis: A systematic review (2021) · cites this paper as [9]
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“The relationship between depression and TB is bidirectional.”
From Pharmacological or non-pharmacological interventions for treatment of common mental disorders associated with Tuberculosis: A systematic review (2021) · cites this paper as [9]
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“Depression may also increase risk of TB reactivation, antibiotic drug resistance, contribute to disease progression, and/or inhibit the physiological response to anti-tuberculosis treatment (ATT).”
From Pharmacological or non-pharmacological interventions for treatment of common mental disorders associated with Tuberculosis: A systematic review (2021) · cites this paper as [9]
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“These mutually reinforcing pathways have been described as a TB–depression syndemic, in which biological, psychological, and social vulnerabilities cluster and amplify each other in low-resource and high-stigma settings [6].”
From Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches. (2026) · cites this paper as [6]
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“the experience of being diagnosed with and treated for TB can precipitate or worsen mental health problems through several pathways”
From Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches. (2026) · cites this paper as [6]
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“This finding is consistent with the conceptualization of TB and depression as a syndemic, in which poverty, undernutrition, stigma, social isolation, medication side effects, and psychological distress may reinforce one another over time [6,7,9].”
From Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches. (2026) · cites this paper as [6]
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Metadata
- Authors
- Sweetland, A. C., Kritski, A., Oquendo, M. A., Sublette, M. E., Norcini Pala, A., Silva, L. R. B., Karpati, A., Silva, E. C., Moraes, M. O., Silva, J. R. L. E., & Wainberg, M. L.
- Affiliations
- New York State Psychiatric Institute (US)
- Universidade Federal do Rio de Janeiro (BR)
- University of Pennsylvania (US)
- Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, New York, USA; New York State Psychiatric Institute, New York, New York, USA
- Vital Strategies (US)
- State University of Norte Fluminense (BR)
- ORCID
- Venue
- The International Journal of Tuberculosis and Lung Disease
- Published
- 2017-08-01
- Volume
- 21
- Issue
- 8
- Pages
- 852-861
- ISSN
- 1027-3719 (ISSN-L)
- PMC
- PMC5759333
- OpenAlex
- W2743140206
- Cited by
- 177
- References
- 85
- Citations by year
- 2026: 17 · 2025: 29 · 2024: 28 · 2023: 23 · 2022: 18 · 2021: 18 · 2020: 21 · 2019: 15 · 2018: 8
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The International Journal of Tuberculosis and Lung Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Arca - Repositório Institucional da Fiocruz (submittedVersion)
- Funders
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- National Institute of Mental Health (T32MH019139, K01MH104514, T32MH096724)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Keywords
- tuberculosis, depression, comorbidities, tuberculosis reactivation, tuberculosis transmission, drug resistance, TB stigma, medication adherence, health-seeking behavior, hypothalamic-pituitary-adrenal axis, inflammation, substance abuse, poverty, malnutrition, integrated care, tuberculosis elimination
- MeSH terms
- Antitubercular Agents, Depression, Humans, Tuberculosis, Health Behavior, Cost of Illness, Disease Progression, Patient-Centered Care, Drug Resistance, Bacterial, Medication Adherence, Social Stigma
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