Mental health symptoms and inflammatory markers among HIV infected patients in Tanzania.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968562 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2458 (Electronic) Linking ISSN: 14712458 NLM ISO Abbreviation: BMC Public Health Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

HIV Infections*/complications ; HIV Infections*/drug therapy ; HIV Infections*/epidemiology ; Mental Disorders*/diagnosis ; Mental Disorders*/epidemiology; Biomarkers ; Cross-Sectional Studies ; Humans ; Mental Health ; Tanzania/epidemiology

Background: HIV and mental disorders are predicted to be the leading causes of illness worldwide by the year 2030. HIV-infected patients are at increased risk of developing mental disorders which are significantly associated with negative clinical outcomes and propagation of new HIV infections. There is little evidence that links inflammation to development of mental disorders among HIV patients. Therefore, the main objective of this study was to evaluate if mental health symptoms were associated with biomarkers of inflammation in HIV infected subjects.
Methods: A cross-sectional study was conducted in Dar es Salam, Tanzania from March to May 2018. Standardized tools were used to collect data based on the World Health Organisation's (WHO) stepwise approach for non-communicable diseases (NCD) surveillance. A total of 407 HIV+ patients on antiretroviral therapy were recruited. The WHO stepwise approach for NCD surveillance was used to collect data together with anthropometric measurements. Mental health symptoms were determined based on self-reported thoughts of helplessness, suicide ideation, depression, despair, discouragement, and feelings of isolation. Enzyme-linked immunosorbent assay was used to test for inflammatory markers:- C-reactive protein (CRP), Iinterleukin-6 (IL-6), interleukin-18 (IL-18), soluble tumour necrosis factor receptor-I (sTNFR-I), and soluble tumour necrosis factor receptor-II (sTNFR-II). Bivariate and multi-variate analysis was conducted to examine the association between biomarkers and mental health symptoms.
Results: The prevalence of self-reported mental health symptoms was 42% (n = 169). Participants with self-reported symptoms of mental health had elevated CRP, were less likely to walk or use a bicycle for at least 10 minutes, were less likely to participate in moderate-intensity sports or fitness activities, and had poor adherence to HIV treatment (p < 0.005). CRP remained significant in the sex adjusted, age-sex adjusted, and age-sex-moderate exercise adjusted models. In the fully adjusted logistic regression model, self-reported mental health symptoms were significantly associated with a higher quartile of elevated CRP (OR 4.4; 95% CI 1.3-5.9) and sTNFR-II (OR 2.6; 95% CI 1.4-6.6) and the third quartile of IL-18 (OR 5.1;95% CI 1.5-17.5) as compared with those reporting no mental health symptoms. The significance of sTNFR-II and IL-18 in the fully adjusted model is confounded by viral load suppression rates at the sixth month.
Conclusion: High CRP and sTNFR II were important contributors to the prevalence of mental health symptoms. This study is among the minimal studies that have examined mental health issues in HIV, and therefore, the findings may offer significant knowledge despite the potential reverse causality. Regardless of the nature of these associations, efforts should be directed toward screening, referral, and follow-up of HIV patients who are at-risk for mental health disorders.

Erratum in: BMC Public Health. 2021 Aug 11;21(1):1535. (PMID: 34380450)

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. https://doi.org/10.1371/journal.pmed.0030442 .
Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS) Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science. 1983;220(4599):868–71. (PMID: 10.1126/science.6189183)
World Health Organization. Progress report on HIV, viral hepatitis and sexually transmitted infections, vol. 2019; 2019. p. 2016–21.
United Nations Joint Programme on HIV/AIDS (UNAIDS). UNAIDS Data. 2019;2019:476.
Whetten K, Reif S, Whetten R, Murphy-Mcmillan LK. Trauma, mental health, distrust, and stigma among HIV-positive persons: implications for effective care. Psychosom Med. 2008;70(5):531–8. https://doi.org/10.1097/PSY.0b013e31817749dc . (PMID: 10.1097/PSY.0b013e31817749dc18541904)
Schadé A, van Grootheest G, Smit JH. HIV-infected mental health patients: characteristics and comparison with HIV-infected patients from the general population and non-infected mental health patients. BMC Psychiatry. 2013;13(1):35. https://doi.org/10.1186/1471-244X-13-35 . (PMID: 10.1186/1471-244X-13-35233433563577506)
Elkington KS, McKinnon K, Mann CG, Collins PY, Leu C-S, Wainberg ML. Perceived mental illness stigma and HIV risk behaviors among adult psychiatric outpatients in Rio de Janeiro, Brazil. Community Ment Health J. 2010;46(1):56–64. https://doi.org/10.1007/s10597-009-9209-4 . (PMID: 10.1007/s10597-009-9209-419543974)
Wainberg ML, Cournos F, Wall MM, Pala AN, Mann CG, Pinto D, et al. Mental illness sexual stigma: implications for health and recovery. Psychiatr Rehabil J. 2016;39(2):90–6. https://doi.org/10.1037/prj0000168 . (PMID: 10.1037/prj0000168270309094900913)
Bonfils KA, Firmin RL, Salyers MP, Eric R. Sexuality and intimacy among people living with serious mental illnesses: Factors contributing to sexual activity. Psychiatr Rehabil J. 2015; 38(3): 249–255.
Ciesla JA, Roberts JE. Meta-Analysis of the Relationship Between HIV Infection and Risk for Depressive Disorders. 2001;158(5):725–30.
Remien RH, Stirratt MJ, Nguyen N, Robbins RN, Pala AN, Mellins CA. Mental health and HIV/AIDS: the need for an integrated response. AIDS. 2019;33(9):1411–20. https://doi.org/10.1097/QAD.0000000000002227 . (PMID: 10.1097/QAD.000000000000222730950883)
Chander G, Himelhoch S, Moore RD. Substance abuse and psychiatric disorders in HIV-positive patients. Drugs. 2006;66(6):769–89. https://doi.org/10.2165/00003495-200666060-00004 . (PMID: 10.2165/00003495-200666060-0000416706551)
Jayarajan N, Chandra PS. HIV and mental health: An overview of research from India. Indian J Psychiatry. 2010;52(Suppl1):S269–S273.
Lee Y-H, Salman A, Fitzpatrick JJ. HIV/AIDS preventive self-efficacy, depressive symptoms, and risky sexual behavior in adolescents: a cross-sectional questionnaire survey. Int J Nurs Stud. 2009;46(5):653–60. https://doi.org/10.1016/j.ijnurstu.2008.11.007 . (PMID: 10.1016/j.ijnurstu.2008.11.00719159880)
Preez A Du, Leveson J, Zunszain PA, Pariante CM. Inflammatory insults and mental health consequences: does timing matter when it comes to depression?. Psychol Med. 2016;46(10):2041–57.
Bondy B. Pathophysiology of depression and mechanisms of treatment. Dialogues Clin Neurosci. 2002;4(1):7–20. (PMID: 10.31887/DCNS.2002.4.1/bbondy)
Farooq RK, Asghar K, Kanwal S, Zulqernain A. Role of inflammatory cytokines in depression: focus on interleukin-1β. Biomed Reports. 2017;6(1):15–20. https://doi.org/10.3892/br.2016.807 . (PMID: 10.3892/br.2016.807)
Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin N Am. 2009;29(2):247–64. https://doi.org/10.1016/j.iac.2009.02.002 . (PMID: 10.1016/j.iac.2009.02.002)
Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31. https://doi.org/10.1016/j.it.2005.11.006 . (PMID: 10.1016/j.it.2005.11.0061631678316316783)
Gialluisi A, Bonaccio M, Di Castelnuovo A, Costanzo S, De Curtis A, Sarchiapone M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L, Moli-Sani Study Investigators. Lifestyle and biological factors influence the relationship between mental health and low-grade inflammation. Brain Behav Immun. 2020;85:4–13. https://doi.org/10.1016/j.bbi.2019.04.041 .
Patel A. Review: the role of inflammation in depression. Psychiatr Danub. 2013;25(Suppl 2):S216–23. (PMID: 23995180)
Lin BD, Alkema A, Peters T, Zinkstok J, Libuda L, Hebebrand J, et al. Assessing causal links between metabolic traits, inflammation and schizophrenia: a univariable and multivariable, bidirectional Mendelian-randomization study. Int J Epidemiol. 2019;48(5):1505–14. https://doi.org/10.1093/ije/dyz176 . (PMID: 10.1093/ije/dyz176315045417070229)
Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008 Jan;214(2):231–41. https://doi.org/10.1002/path.2276 . (PMID: 10.1002/path.227618161758)
Merrill JE, Martínez-Maza O. Cytokines in AIDS-Associated Nervous and Immune System Dysfunction. In 1993. p. 243–266.
Weiss L, Haeffner-Cavaillon N, Laude M, Gilquin J, Kazatchkine MD. HIV infection is associated with the spontaneous production off interleukin-1 (IL-1) in vivo and with an abnormal release off IL-1αaL in vitro. AIDS. 1989;3(11):695–700. https://doi.org/10.1097/00002030-198911000-00002 . (PMID: 10.1097/00002030-198911000-000022515876)
Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother. 2001;12(3):133–50. https://doi.org/10.1177/095632020101200301 . (PMID: 10.1177/09563202010120030112959322)
Schiepers OJG, Wichers MC, Maes M. Cytokines and major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29(2):201–17. https://doi.org/10.1016/j.pnpbp.2004.11.003 . (PMID: 10.1016/j.pnpbp.2004.11.003)
Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine. 1997;9(11):853–8. https://doi.org/10.1006/cyto.1997.0238 . (PMID: 10.1006/cyto.1997.02389367546)
Norcini Pala A, Steca P, Bagrodia R, Helpman L, Colangeli V, Viale P, et al. Subtypes of depressive symptoms and inflammatory biomarkers: an exploratory study on a sample of HIV-positive patients. Brain Behav Immun. 2016;56:105–13. https://doi.org/10.1016/j.bbi.2016.02.013 . (PMID: 10.1016/j.bbi.2016.02.01326883521)
Paykel ES. Life events and affective disorders. Acta Psychiatr Scand. 2003;108(s418):61–6. https://doi.org/10.1034/j.1600-0447.108.s418.13.x . (PMID: 10.1034/j.1600-0447.108.s418.13.x)
Slavich GM. Life stress and health. Teach Psychol. 2016;43(4):346–55. https://doi.org/10.1177/0098628316662768 . (PMID: 10.1177/009862831666276850665705066570)
Hardy P, Gorwood P. [Impact of life events in the course of depression]. Encephale. 1993;19 Spec No:481–9.
Brown GW. Life events and endogenous depression. Arch Gen Psychiatry. 1994;51(7):525–34. https://doi.org/10.1001/archpsyc.1994.03950070017006 . (PMID: 10.1001/archpsyc.1994.039500700170068031225)
Kendler KS, Thornton LM, Prescott CA. Gender differences in the rates of exposure to stressful life events and sensitivity to their Depressogenic effects. Am J Psychiatry. 2001;158(4):587–93. https://doi.org/10.1176/appi.ajp.158.4.587 . (PMID: 10.1176/appi.ajp.158.4.58711282693)
Berrettini WH. Molecular linkage studies of bipolar disorders. Bipolar Disord. 2001;3(6):276–83. https://doi.org/10.1034/j.1399-5618.2001.30603.x . (PMID: 10.1034/j.1399-5618.2001.30603.x11843778)
Nkinda L, Patel K, Njuguna B, Ngangali JP, Memiah P, Bwire GM, et al. C - Reactive protein and interleukin - 6 levels among human immunodeficiency virus -infected patients with dysglycemia in Tanzania. BMC Endocr Disord. 2019;19(1):77. [cited 2021 Apr 10] Available from: https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-019-0407-y .
Riley L, Guthold R, Cowan M, Savin S, Bhatti L, Armstrong T, et al. The world health organization STEPwise approach to noncommunicable disease risk-factor surveillance: methods, challenges, and opportunities. Am J Public Health. 2016;106(1):74–8. https://doi.org/10.2105/AJPH.2015.302962 . (PMID: 10.2105/AJPH.2015.302962266962884695948)
The Medical Outcomes Study HIV Health Survey (MOS-HIV). https://www.jhsph.edu/research/affiliated-programs/medical-outcomes-study-HIV/ . Accessed  27 Jan 2021.
STEPwise Approach to NCD Risk Factor Surveillance (STEPS). https://www.who.int/teams/noncommunicable-diseases/surveillance/systems-tools/steps . Accessed 1 Dec 2020.
Clyne B, Olshaker JS. The C-reactive protein. J Emerg Med. 1999;17(6):1019–25. https://doi.org/10.1016/S0736-4679(99)00135-3 . (PMID: 10.1016/S0736-4679(99)00135-310595891)
Lau B, Sharrett AR, Kingsley LA, Post W, Palella FJ, Visscher B, Gange SJ. C-reactive protein is a marker for human immunodeficiency virus disease progression. Arch Intern Med. 2006;166(1):64–70. https://doi.org/10.1001/archinte.166.1.64 .
Boulware DR, Hullsiek KH, Puronen CE, Rupert A, Baker JV, French MA, et al. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis. 2011;203(11):1637–46. https://doi.org/10.1093/infdis/jir134 . (PMID: 10.1093/infdis/jir134215929943096784)
Shivakoti R, Yang WT, Berendes S, Mwelase N, Kanyama C, Pillay S, et al. Persistently elevated C-reactive protein level in the first year of antiretroviral therapy, despite virologic suppression, is associated with HIV disease progression in resource-constrained settings. J Infect Dis. 2016;213(7):1074–8. https://doi.org/10.1093/infdis/jiv573 . (PMID: 10.1093/infdis/jiv57326621909)
Poudel-Tandukar K, Bertone-Johnson ER, Palmer PH, Poudel KC. C-reactive protein and depression in persons with human immunodeficiency virus infection: the positive living with HIV (POLH) study. Brain Behav Immun. 2014;42:89–95. https://doi.org/10.1016/j.bbi.2014.06.004 . (PMID: 10.1016/j.bbi.2014.06.00424929193)
Kim JR, Kim HN, Song SW. Associations among inflammation, mental health, and quality of life in adults with metabolic syndrome. Diabetol Metab Syndr. 2018;10(1):66. https://doi.org/10.1186/s13098-018-0367-9 . (PMID: 10.1186/s13098-018-0367-9301863716119265)
Kokai M, Kashiwamura SI, Okamura H, Ohara K, Morita Y. Plasma interleukin-18 levels in patients with psychiatric disorders. J Immunother. 2002;25(Suppl 1):S68–71.
Xu Y, Yue W, Shugart YY, Yuan J, Wang G, Wang HZ, et al. Potential involvement of the interleukin-18 pathway in schizophrenia. J Psychiatr Res. 2016;74:10–6. https://doi.org/10.1016/j.jpsychires.2015.12.013 . (PMID: 10.1016/j.jpsychires.2015.12.01326736035)
Wedervang-Resell K, Friis S, Lonning V, Smelror RE, Johannessen C, Reponen EJ, et al. Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms. Psychoneuroendocrinology. 2020;112:104513. https://doi.org/10.1016/j.psyneuen.2019.104513 . (PMID: 10.1016/j.psyneuen.2019.10451331761332)
Bossù P, Piras F, Palladino I, Iorio M, Salani F, Ciaramella A, et al. Hippocampal volume and depressive symptoms are linked to serum IL-18 in schizophrenia. Neurol Neuroimmunol NeuroInflammation. 2015;2(4):e111. https://doi.org/10.1212/NXI.0000000000000111 . (PMID: 10.1212/NXI.0000000000000111)
Mansur RB, Cunha GR, Asevedo E, Zugman A, Rizzo LB, Grassi-Oliveira R, et al. Association of serum interleukin-6 with mental health problems in children exposed to perinatal complications and social disadvantage. Psychoneuroendocrinology. 2016;71:94–101. https://doi.org/10.1016/j.psyneuen.2016.05.015 . (PMID: 10.1016/j.psyneuen.2016.05.01527258821)
Teixeira AL, De Souza RT, Zanetti MV, Brunoni AR, Busatto GF, Zarate CA, et al. Increased plasma levels of soluble TNF receptors 1 and 2 in bipolar depression and impact of lithium treatment. Hum Psychopharmacol. 2015;30(1):52–6. https://doi.org/10.1002/hup.2450 . (PMID: 10.1002/hup.2450255723095858728)
Diniz BS, Teixeira AL, Talib LL, Mendonça VA, Gattaz WF, Forlenza OV. Increased soluble TNF receptor 2 in antidepressant-free patients with late-life depression. J Psychiatr Res. 2010;44(14):917–20. https://doi.org/10.1016/j.jpsychires.2010.02.008 . (PMID: 10.1016/j.jpsychires.2010.02.00820338581)
Postal M, Lapa AT, Sinicato NA, et al. Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus. J Neuroinflammation. 2016;13:5. https://doi.org/10.1186/s12974-015-0471-9 .
Kudo N, Yamamori H, Ishima T, Nemoto K, Yasuda Y, Fujimoto M. Plasma levels of soluble tumor necrosis factor receptor 2 (STNFR2) are associated with hippocampal volume and cognitive performance in patients with schizophrenia. Int J Neuropsychopharmacol. 2018;21(7):631–9. https://doi.org/10.1093/ijnp/pyy013 . (PMID: 10.1093/ijnp/pyy013295292896031046)
Wium-Anderson MK, Orsted DD, Nielsen SF, Nordestgaard BG. Elevated C-reactive protein levels, psychological distres, and depression in 73131 individuals. JAMA Psychiatry. 2013;70(2):176–84. https://doi.org/10.1001/2013.jamapsychiatry.102 . (PMID: 10.1001/2013.jamapsychiatry.102)
Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011;13(6):467–75. https://doi.org/10.1007/s11920-011-0232-0 . (PMID: 10.1007/s11920-011-0232-0219278053285451)
Capuron L, Miller AH. Pharmacology & Therapeutics Immune system to brain signaling : Neuropsychopharmacological implications ☆. Pharmacol Ther. 2011;130(2):226–38. https://doi.org/10.1016/j.pharmthera.2011.01.014 . (PMID: 10.1016/j.pharmthera.2011.01.014213343763072299)
Hashimoto K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev. 2009;61(2):105–23. https://doi.org/10.1016/j.brainresrev.2009.05.005 . (PMID: 10.1016/j.brainresrev.2009.05.00519481572)
Giudicessi JR, Ackerman BM. 2013. 基因的改变NIH public access. Bone. 2008;23(1):1–7.
Duivis HE, de Jonge P, Penninx BW, Na BY, Cohen BE, Whooley MA. Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study. Am J Psychiatry. 2011;168(9):913–20.
Diane E. Handy, Rita Castro JL. 基因的改变NIH public access. Bone. 2011;23(1):1–7.
Kim JW, Szigethy EM, Melhem NM, Saghafi EM, Brent DA. Inflammatory markers and the pathogenesis of pediatric depression and suicide: a systematic review of the literature. J Clin Psychiatry. 2014;75(11):1242–53. https://doi.org/10.4088/JCP.13r08898 . (PMID: 10.4088/JCP.13r0889825470085)
Kyrou I, Tsigos C. Stress hormones: physiological stress and regulation of metabolism. Curr Opin Pharmacol. 2009;9(6):787–93. https://doi.org/10.1016/j.coph.2009.08.007 . (PMID: 10.1016/j.coph.2009.08.00719758844)
Wilson M, Wilson M. Men and women. Men Elders. 2018;19(2):106–41. (PMID: 10.4324/9780429470981-6)
Gialluisi A, de Gaetano G, Iacoviello L. New challenges from Covid-19 pandemic: an unexpected opportunity to enlighten the link between viral infections and brain disorders? Neurol Sci. 2020;41:1349–50.  https://doi.org/10.1007/s10072-020-04444-z .
Kinyanda E, Hoskins S, Nakku J, Nawaz S, Patel V. Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda. BMC Psychiatry. 2011;11:205.
Jonsson G, Davies N, Freeman C, Joska J, Pahad S, Thom R, et al. Guideline: management of mental health disorders in HIV-positive patients. South Afr J HIV Med. 2013;14(4):155–65. (PMID: 10.4102/sajhivmed.v14i4.50)
Bhatia MS, Munjal S. Prevalence of depression in people living with HIV/AIDS undergoing art and factors associated with it. J Clin Diagnostic Res. 2014;8(10):WC01–4.
Niu L, Luo D, Liu Y, Silenzio VMB, Xiao S. The mental health of people living with HIV in China, 1998-2014: a systematic review. PLoS One. 2016;11(4):e0153489. https://doi.org/10.1371/journal.pone.0153489 . (PMID: 10.1371/journal.pone.0153489270827494833336)
Ali GC, Ryan G, De Silva MJ. Validated screening tools for common mental disorders in low and middle income countries: a systematic review. PLoS One. 2016;11(6):1–15.

Keywords: Antiretroviral; Dar Es Salaam; Inflammatory markers; Mental health; People living with HIV

0 (Biomarkers)

Date Created: 20210611 Date Completed: 20210701 Latest Revision: 20210812

20221213

PMC8193867

10.1186/s12889-021-11064-5

34112126