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

BMC Public Health volume 21, Article number: 1113 (2021) Cite this article

A Correction to this article was published on 11 August 2021

This article has been updated

Abstract

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.

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Background

Human immunodeficiency virus (HIV) and mental disorders are predicted to be the leading causes of illness worldwide by the year 2030 [1]. Tremendous progress has been made globally since HIV – type 1 (HIV-1) was discovered in 1983 [2], with acquired immunodeficiency syndrome (AIDS) related annual deaths declining by 33% from 2010 to about 770,000 in 2018 [3, 4]. People living with HIV (PLHIV) face many negative experiences including stigma, discrimination, traumatic events, and mental health problems [5, 6]. These negative experiences increase the risk of developing mental disorders in PLHIV [5, 6]. HIV un-infected people with mental health problems have a higher risk of HIV infection than the general population [7,8,9,10] with severe mental illness increasing the risk of HIV acquisition by 4 to 10 fold [11]. Psychiatric disorders among HIV-infected individuals are significantly associated with negative clinical outcomes including reduced highly active antiretroviral therapy (HAART) utilization, poor adherence to HAART, and poor virological suppression [6, 12, 13]. On the other hand, mental health problems increase risky sexual behaviors like unprotected sex and multiple sexual partners which exacerbate the probability of spreading HIV [5, 6, 14]. Depressive symptoms are the most common form of mental disorders in HIV-1 infected patients and can also be a side effect of HAART [6, 13].

It is widely recognized that increased levels of inflammation are central to the development of mental health problems like depression [15,16,17,18,19]. Recent studies indicate a bi-directional relationship [20]. Notwithstanding, the evidence linking inflammation to mental disorders comes from observations of elevated levels of inflammatory markers in patients with mental health problems, co-occurrence of mental health problems with inflammatory illnesses, and increased risk of mental health problems with cytokine treatment [21, 22]. Following HIV-1 infection, the establishment of immune activation and inflammation involve several mechanisms that are directly or indirectly related to viral replication [23]. High levels of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNFα), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β) in both plasma and lymph nodes, are observed from the early stages of HIV-1 infection [24,25,26]. In vitro studies suggest that HIV gene products can induce directly the activation of lymphocytes and macrophages and the production of pro-inflammatory cytokines and chemokines [23, 24]. There is evidence to support the ‘cytokine hypothesis of depression’ which implies that pro-inflammatory cytokines, acting as neuromodulators, represent the key factor in the mediation of the behavioral, neuroendocrine, and neurochemical features of depressive disorders [27]. This hypothesis was emphasized by findings of increased plasma cytokines (IL-1 and IL-6) in the blood of depressed patients [28]. More robust research measuring direct markers of inflammation and mental health is needed among HIV-1 infected patients [15, 29].

Besides HIV/AIDS, there are other risk factors for increased risk of mental disorders. The impact of chronic stress and adverse life events on the onset of depression has been investigated repeatedly, partly influenced by studies of the somatic and endocrine consequences of stress in animals [16]. There is association of severely life-threatening events prior to onset of mental disorders such as depression, anxiety disorders, and affective disorders [30,31,32]. However, research has not shown the expected clear-cut difference in the presence of adverse life events provoking onset in depression [33]. The prevalence of depression is higher in females than males, and this cannot be explained by differing rates of exposure to stressful life events [16, 34]. There is also evidence that genetic factors play an important role in the etiology of affective disorders [16, 35].

As there is strong evidence of deranged inflammatory response in HIV-1 as well as in mental health disorders, we set out to assess markers related to the inflammation in HIV-1 infected subjects with and without mental health symptoms. We posit that mental health symptoms lead to increased pro-inflammatory cytokine levels (CRP, IL-6, IL-18, sTNFR I, sTNFR II) in HIV-1 infected subjects.

Methods

Study design, site, and population

The study adopted a cross-sectional study design. Data was collected from PLHIV receiving treatment at the Infectious Disease Clinic (IDC) between March to May 2018. The Clinic is located in Dar es Salaam, Tanzania and provides care and treatment to a high proportion of PLHIV with an estimated 100 patients per day. Adults (> 18 years) living with HIV/AIDS, receiving care at IDC, and consented to be part of the study were included. The exclusion criteria was patients who were on antihypertensives and anti-inflammatory drugs within the past 3 months [36].

Sample size and sampling technique

This study recruited 407 HIV-positive study participants on Antiretroviral Therapy (ART). Purposive sampling was used whereby HIV patients attending appointments were screened, consented, and were recruited into the study.

Data collection

The study entailed quantitative data collection through survey, review of medical records, anthropometry, blood pressure assessments, and biochemical assessment of biomarkers in blood samples. The survey utilised the WHO Steps tool for NCD surveillance [37] to collect demographic and behavioural characteristics of participants [36]. Data on CD4 count, types, and duration of a ART was extracted from medical records. A trained nurse took blood pressure measurements as well as measurements of weight, height, and waist circumference.

Blood pressure measurements

Diastolic and systolic blood pressure measurements were taken using an Omron M2 (HEM-7121-E). This is a clinically validated automated blood pressure monitor. Two measurements were taken twice from the upper left arm at 3 minute intervals when the participant was seated and relaxed [36]. An average of the two readings was calculated and used in analysis. In order to diagnose hypertension, an average reading of greater than 140/90 mmHg was used.

Anthropometric measurements

Anthropometric measurements included waist and hip circumeference (cm), body weight (kg), and height (meters). Standard procedures of taking measurements were observed. For waist and height circumference measurements, waist to height ratio (WHR) was calculated in which > 50% was considered to represent an elevated WHR. Additionally, body mass index (BMI) was calculated based on weight and height, and the following cut-offs were used: under-weight (BMI < 18 kg/m2), normal (BMI ≥ 18 kg/m2 and ≤ 25 kg/m2), overweight (BMI > 25 kg/m2 and < 30 kg/m2), and obese (BMI ≥ 30 kg/m2) [36].

Blood sample collection and handling

This part of the process entailed collection of venous blood by trained phlebotomists. The blood samples were collected into Ethylenediaminetetraacetic acid (EDTA) tubes. In order to obtain blood serum, the sample collected centrifuges for 20 minutes at 1000×g, and serum obtained was stored in cryo vials at − 80 °C. Using the Enzyme Linked Immunosorbent Assay (ELISA) reader and the Multiskan Ascent reader 354–90,593 [36], anti-inflammatory markers, including interleukin 6 (IL-6), C-reactive protein (CRP), interleukin 18 (IL18), soluble tumour necrosis factor receptor type I (sTNFR-I) and type II (sTNFR-II), were tested. The laboratory procedures for analyzing these inflammatory markers are fully described in our related manuscript [36].

Self-reported mental health symptoms

The outcome variable was defined as feelings of depression, suicide ideation, low energy, helplessness, despair, and isolation in the last 30 days. We used the HIV Medical Outcomes Survey (MOS-HIV) which is a widely used and accepted measure for Health Related Quality of Life (HRQOL) in the HIV population [38]. The instrument has 35 items that assess the ten dimensions of health in individuals living with HIV (mental health, quality of life, health distress, cognitive function, and energy/fatigue). The outcome variable score was collapsed and categorized as a dichotomous variable with a “Yes” if the respondent answered yes to any of the questions on mental health and “No” if they answered no to all the questions. Some of the questions asked whether the participant was feeling down, depressed or hopeless; had poor appetite or overeating; had trouble concentrating on things such as reading; and had little interest or pleasure in doing things. The MOS-HIV tool was integrated with the WHO Stepwise approach tool [39], the primary tool for this study.

Data analysis

Microsoft Excel was used for entry of data from case reports forms and the ELISA reader. After which the data was clean and exported to STATA 14 (StataCorp, College Station, Texas) for coding and statistical analysis. Descriptive analysis of patient characteristics was performed using frequencies, percentages, median, and interquartile range. Analysis of inflammatory markers entailed stratification of the data into centiles then frequencies and percentages derived. Chi-square tests were used to determine whether there were any differences by sex and mental health status. At the multivariate level, four models, including sex-adjusted, age-sex adjusted, age-sex-moderate exercise adjusted, and the full multivariable model that included only covariates that had a priori p-value < 0.1 with mental health in the univariate models, were utilised. Unadjusted and adjusted odds ratios (OR) were utilised to report associations between the variables. A p-value < 0.05 was statistically significant.

Result

Participants characteristics – males vs females

We collected data from 407 participants, 99 males and 308 females, and summarized their characteristics in Table 1. Compared to females, males were less likely to be both overweight (21.4% vs 27.7%; P < 0.001) and obese (5.1% vs 18.6%; P < 0.001), respectively. There was a higher proportion of males compared to females in participants who were over 55 years (67.7% vs 59.7%; P < 0.037). Male participants had less prevalent abnormal waist hip ratio compared to female participants (16.3% vs 97.1%; P < 0.001). Compared to females, male participants had a greater prevalence of currently smoking tobacco products (9.1% vs 1%; P < 0.001), consumption of alcohol within past 12 months (35.5% vs 15.7%; P < 0.01), and consumption of alcohol within the past 30 days (19.4% vs 9.8%; P < 0.05).

Table 1 Characteristics of mental health symptoms among HIV+ patients in Tanzania
Full size table

Compared to males, females were less likely to be involved in vigorous-intensity work (13.1% vs 1.6%; P < 0.001). Male participants were more likely to walk or use a bicycle for at least 10 minutes compared to female participants (57.6% vs 41.2%; P < 0.05). Compared to males, females were less likely to participate in moderate-intensity sports or fitness activities (13.1% vs 2.9%: P < 0.001). Males were more likely to have elevated TNR-2 as compared to females (23.3% vs 21.3%; P < 0.05) as indicated in Table 2.

Table 2 Characteristics of mental health symptoms and physical activity among HIV+ patients in Tanzania
Full size table

Participants' characteristics – self reported mental health symptoms vs no mental health symptoms

169 (42%) participants had self-reported mental health symptoms compared to 233 (58%) participants who reported none. Participants with self-reported symptoms of mental health had elevated CRP (32.1% vs 19.1%; P < 0.05) compared to those without. Participants with self-reported mental health symptoms were less likely to walk or use a bicycle for at least 10 minutes compared to those without (36.7% vs 51.9%; P < 0.05). Compared to those with self-reported mental health symptoms, participants without mental illness were less likely to participate in moderate-intensity sports or fitness activities (7.1% vs 2.1%: P < 0.05) and vigorous activities (8.3% vs 3%: P < 0.05).

Participants with self-reported mental health symptoms had lower ART adherence in the past week (14.9% vs 4.3%; P < 0.05) and in the past month (18.9% vs 11.2%; P < 0.05) compared with those without mental health symptoms (Table 3).

Table 3 Characteristics of mental health symptoms and clinical variables among HIV+ patients in Tanzania
Full size table

There was a significant difference in elevated CRP (p = 0.013) and sTNFR-II (p = 0.036) between participants who had mental health symptoms and no health symptoms (Table 4).

Table 4 Characteristics of mental health symptoms and inflammatory markers among HIV+ patients in Tanzania
Full size table

Odds ratio tables

In the sex-adjusted model, CRP was significant (OR 2.27; 95% CI 1.24–4.16) and was also observed to be significant in the age-sex adjusted model (OR 2.14; 95% CI 1.15–3.96) and the age-sex-moderate exercise model (OR 2.14; 95% CI 1.14–4). No other significant associations between biomarkers (pro-inflammatory markers) and self-reported mental health symptoms were present after multivariable adjustment. In the full adjusted logistic regression model, those in the highest quartile (Q4) of CRP (OR 4.37; 95% CI 1.28–5.88) and TNR-2 (OR 2.61; 95% CI 1.39–6.66) had a higher odds of having mental health symptoms (Table 5).

Table 5 Logistic regression on mental health symptoms
Full size table

Discussion

CRP has long been regarded as an acute phase protein indicative of ongoing infectious or inflammatory disease states, and is an identified marker associated with HIV disease [36, 40,41,42,43,44]. In a purposive sample of HIV positive Tanzanian adults, we found that elevated levels of CRP were positively associated with self-reported mental health symptoms. The observed association was independent of potential confounders such as age, WHR, physical activity, family history of diabetes, viral load (VL), and TNR2. To our knowledge, this study is the first to report on the positive association between CRP and self-reported mental health symptoms among HIV patients in Tanzania. This is consistent with data from the Korean National Health and Nutrition Examination Survey (KNH&NES) which correlated elevation in hs-CRP with mobility problems and suicidal ideation leading to decreased quality of life and mental health problems [45]. Despite other inflammatory markers (IL-6, IL-18, and sTNFR-I) assessed in our study not showing any significant association with mental health symptoms, other studies have shown a link between these markers and mental health symptoms [46,47,48,49,50,51,52]. Notwithstanding, none of the studies were conducted among HIV populations.

Despite the complicated and unexplored link between mental health and inflammation, activation of the sTNFR-II in patients with chronic inflammatory conditions appears to mediate depression through stimulation of a neuronal serotonin pathway leading to depletion of tryptophan [20, 53]. This may help explain the significant association between sTNFR-II levels and mental health symptoms in our study population. If uninterrupted, sustained elevations of sTNFR-II have been postulated to lead to smaller hippocampal volumes and ultimately cognitive impairment [54].

While the pathogenesis of mental illness is not clearly understood, the association of CRP, sTNFR-II, and mental health symptoms in the study population suggests an association between a proinflammatory state and psychological distress in the population [55]. This may stem from an increase in the production of kynurenic and quinolinic acids associated with activation of the enzyme indoleamine-2,3-dioxygenase that leads to a reduction in the production of serotonin, which contributes to the development of depression [56, 57]. Further, increased neurotransmitter glutamate is associated with an increase in the production of kynurenic and quinolinic acids and may result in reduced brain-derived neurotrophic factor that is widely associated with depression [58].

It is also possible that the observed association could be due to reverse causality. Having symptoms of mental health may lead to increased inflammation [59,60,61,62]. Stress hormones released during psychological stress may trigger systemic inflammation resulting in elevated levels of CRP and sTNFR-II [63]. On the other hand, HIV disease itself may serve as a trigger for inflammation that may affect mental health. Even in the era of widespread use of ART, neuropsychiatric conditions, such as anxiety disorders, manic symptoms, atypical psychosis, or depression, continue to occur in HIV patients [64, 65]. Compared to the general population, significantly higher rates of mental health disorders have been reported among PLWH elsewhere. Among PLWH in Uganda, the prevalence of major depression was 14% [66]. Approximately, 26–38% of PLWH in South Africa have a mental disorder [67]. In India and China, the prevalence of depression symptoms among PLWH were 59% and 61% of PLWH, respectively [68, 69].

Regardless of the nature of the relationship between inflammation and mental health, our study findings support the need to screen HIV infected patients for symptoms and provide follow-up care as part of of HIV care. There is a plethora of well-established and validated instruments for mental health screening that can be utilized in low-and middle-income countries (LMICs) [70]. The results also support the need for additional intervention studies aimed at improving mental health outcomes in HIV patients.

Our study was limited by lack of a validated instrument or diagnostic scoring scale to measure specific mental health outcomes such as anxiety, psychological distress, or depression. Given the cross-sectional nature of the study, we cannot establish the direction of the relationship between CRP and sTNFR-II and mental health outcomes. The main outcome of interest, symptoms of mental health, was based on self-report, which is susceptible to social desirability and self-report bias. Additionally, purposive sampling may have introduced selection bias. As such, results may not be generalizable to the entire PLWH population in Tanzania. Finally, the observed association might also be due to unmeasured confounding, such as antidepressant use, and other factors associated with mental health outcomes that was not collected for this study. Despite these limitations our study is strengthened by being amongst the pioneer studies that show an association between inflammation and mental health symptoms among PLWH from a HIV high-burden country.

Conclusion

Our study found that in a sample of Tanzanian adults, elevated levels of pro-inflammatory cytokines, including CRP and sTNFR-II, was positively associated with self-reported mental health symptoms, independent of confounding. However, due to potential reverse causality and confounding, findings from the current study should be interpreted with caution. Regardless of the nature of these associations, efforts should be made to screen for mental health disorders in HIV patients with structured follow-up for those found at risk.

Availability of data and materials

Data used in the analyses for this study are available upon request from the corresponding author.

Change history

Abbreviations

AIDS:

Acquired Immunodeficiency Syndrome

ART:

Antiretroviral Therapy

BMI:

Body Mass Index

CI:

Confidence Interval

CRP:

C-reactive Protein

CRF:

Case Report Forms

EDTA:

Ethylenediaminetetraacetic Acid

ELISA:

Enzyme-Linked Immunosorbent Assay

HAART:

Highly Active Antiretroviral Therapy

HIV:

Human Immunodeficiency Virus

HIV-1:

Human Immunodeficiency Virus Type 1

HRQOL:

Health-Related Quality of Life

IDC:

Infectious Disease Clinic

IL-6:

Interleukin-6

IL-18:

Interleukin-18

MBL:

Medical and Biological Laboratories

MOS-HIV:

Medical Outcomes Survey for HIV

NCD:

Non-Communicable Disease

OR:

Odds Ratio

PLHIV:

People Living with HIV

sTNFR I:

Soluble Tumour Necrosis Factor Receptor-I

sTNFRII:

Soluble Tumour Necrosis Factor Receptor-II

WHO:

World Health Organization

WHR:

Waist to Height Ratio

References

  1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. https://0-doi-org.brum.beds.ac.uk/10.1371/journal.pmed.0030442.

  2. 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.

    Article  PubMed  Google Scholar 

  3. World Health Organization. Progress report on HIV, viral hepatitis and sexually transmitted infections, vol. 2019; 2019. p. 2016–21.

    Google Scholar 

  4. United Nations Joint Programme on HIV/AIDS (UNAIDS). UNAIDS Data. 2019;2019:476.

    Google Scholar 

  5. 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://0-doi-org.brum.beds.ac.uk/10.1097/PSY.0b013e31817749dc.

    Article  PubMed  Google Scholar 

  6. 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://0-doi-org.brum.beds.ac.uk/10.1186/1471-244X-13-35.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 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://0-doi-org.brum.beds.ac.uk/10.1007/s10597-009-9209-4.

    Article  PubMed  Google Scholar 

  8. 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://0-doi-org.brum.beds.ac.uk/10.1037/prj0000168.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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.

  10. Ciesla JA, Roberts JE. Meta-Analysis of the Relationship Between HIV Infection and Risk for Depressive Disorders. 2001;158(5):725–30.

  11. 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://0-doi-org.brum.beds.ac.uk/10.1097/QAD.0000000000002227.

    Article  PubMed  Google Scholar 

  12. Chander G, Himelhoch S, Moore RD. Substance abuse and psychiatric disorders in HIV-positive patients. Drugs. 2006;66(6):769–89. https://0-doi-org.brum.beds.ac.uk/10.2165/00003495-200666060-00004.

    Article  PubMed  Google Scholar 

  13. Jayarajan N, Chandra PS. HIV and mental health: An overview of research from India. Indian J Psychiatry. 2010;52(Suppl1):S269–S273.

  14. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.ijnurstu.2008.11.007.

    Article  PubMed  Google Scholar 

  15. 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.

  16. Bondy B. Pathophysiology of depression and mechanisms of treatment. Dialogues Clin Neurosci. 2002;4(1):7–20.

    Article  Google Scholar 

  17. 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://0-doi-org.brum.beds.ac.uk/10.3892/br.2016.807.

    Article  CAS  Google Scholar 

  18. Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin N Am. 2009;29(2):247–64. https://0-doi-org.brum.beds.ac.uk/10.1016/j.iac.2009.02.002.

    Article  Google Scholar 

  19. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27(1):24–31. https://0-doi-org.brum.beds.ac.uk/10.1016/j.it.2005.11.006.

    Article  CAS  PubMed  Google Scholar 

  20. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.bbi.2019.04.041.

  21. Patel A. Review: the role of inflammation in depression. Psychiatr Danub. 2013;25(Suppl 2):S216–23.

    PubMed  Google Scholar 

  22. 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://0-doi-org.brum.beds.ac.uk/10.1093/ije/dyz176.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008 Jan;214(2):231–41. https://0-doi-org.brum.beds.ac.uk/10.1002/path.2276.

    Article  CAS  PubMed  Google Scholar 

  24. Merrill JE, Martínez-Maza O. Cytokines in AIDS-Associated Nervous and Immune System Dysfunction. In 1993. p. 243–266.

  25. 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://0-doi-org.brum.beds.ac.uk/10.1097/00002030-198911000-00002.

    Article  CAS  PubMed  Google Scholar 

  26. Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother. 2001;12(3):133–50. https://0-doi-org.brum.beds.ac.uk/10.1177/095632020101200301.

    Article  CAS  PubMed  Google Scholar 

  27. Schiepers OJG, Wichers MC, Maes M. Cytokines and major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29(2):201–17. https://0-doi-org.brum.beds.ac.uk/10.1016/j.pnpbp.2004.11.003.

    Article  CAS  Google Scholar 

  28. 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://0-doi-org.brum.beds.ac.uk/10.1006/cyto.1997.0238.

    Article  CAS  PubMed  Google Scholar 

  29. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.bbi.2016.02.013.

    Article  CAS  PubMed  Google Scholar 

  30. Paykel ES. Life events and affective disorders. Acta Psychiatr Scand. 2003;108(s418):61–6. https://0-doi-org.brum.beds.ac.uk/10.1034/j.1600-0447.108.s418.13.x.

    Article  Google Scholar 

  31. Slavich GM. Life stress and health. Teach Psychol. 2016;43(4):346–55. https://0-doi-org.brum.beds.ac.uk/10.1177/0098628316662768.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hardy P, Gorwood P. [Impact of life events in the course of depression]. Encephale. 1993;19 Spec No:481–9.

  33. Brown GW. Life events and endogenous depression. Arch Gen Psychiatry. 1994;51(7):525–34. https://0-doi-org.brum.beds.ac.uk/10.1001/archpsyc.1994.03950070017006.

    Article  CAS  PubMed  Google Scholar 

  34. 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://0-doi-org.brum.beds.ac.uk/10.1176/appi.ajp.158.4.587.

    Article  CAS  PubMed  Google Scholar 

  35. Berrettini WH. Molecular linkage studies of bipolar disorders. Bipolar Disord. 2001;3(6):276–83. https://0-doi-org.brum.beds.ac.uk/10.1034/j.1399-5618.2001.30603.x.

    Article  CAS  PubMed  Google Scholar 

  36. 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://0-bmcendocrdisord-biomedcentral-com.brum.beds.ac.uk/articles/10.1186/s12902-019-0407-y.

  37. 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://0-doi-org.brum.beds.ac.uk/10.2105/AJPH.2015.302962.

    Article  PubMed  PubMed Central  Google Scholar 

  38. The Medical Outcomes Study HIV Health Survey (MOS-HIV). https://www.jhsph.edu/research/affiliated-programs/medical-outcomes-study-HIV/. Accessed  27 Jan 2021.

  39. STEPwise Approach to NCD Risk Factor Surveillance (STEPS). https://www.who.int/teams/noncommunicable-diseases/surveillance/systems-tools/steps. Accessed 1 Dec 2020.

  40. Clyne B, Olshaker JS. The C-reactive protein. J Emerg Med. 1999;17(6):1019–25. https://0-doi-org.brum.beds.ac.uk/10.1016/S0736-4679(99)00135-3.

    Article  CAS  PubMed  Google Scholar 

  41. 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://0-doi-org.brum.beds.ac.uk/10.1001/archinte.166.1.64.

  42. 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://0-doi-org.brum.beds.ac.uk/10.1093/infdis/jir134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 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://0-doi-org.brum.beds.ac.uk/10.1093/infdis/jiv573.

    Article  CAS  PubMed  Google Scholar 

  44. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.bbi.2014.06.004.

    Article  CAS  PubMed  Google Scholar 

  45. 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://0-doi-org.brum.beds.ac.uk/10.1186/s13098-018-0367-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 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.

  47. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.jpsychires.2015.12.013.

    Article  PubMed  Google Scholar 

  48. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.psyneuen.2019.104513.

    Article  PubMed  Google Scholar 

  49. 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://0-doi-org.brum.beds.ac.uk/10.1212/NXI.0000000000000111.

    Article  Google Scholar 

  50. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.psyneuen.2016.05.015.

    Article  CAS  PubMed  Google Scholar 

  51. 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://0-doi-org.brum.beds.ac.uk/10.1002/hup.2450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 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://0-doi-org.brum.beds.ac.uk/10.1016/j.jpsychires.2010.02.008.

    Article  PubMed  Google Scholar 

  53. 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://0-doi-org.brum.beds.ac.uk/10.1186/s12974-015-0471-9.

  54. 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://0-doi-org.brum.beds.ac.uk/10.1093/ijnp/pyy013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 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://0-doi-org.brum.beds.ac.uk/10.1001/2013.jamapsychiatry.102.

    Article  CAS  Google Scholar 

  56. Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011;13(6):467–75. https://0-doi-org.brum.beds.ac.uk/10.1007/s11920-011-0232-0.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Capuron L, Miller AH. Pharmacology & Therapeutics Immune system to brain signaling : Neuropsychopharmacological implications ☆. Pharmacol Ther. 2011;130(2):226–38. https://0-doi-org.brum.beds.ac.uk/10.1016/j.pharmthera.2011.01.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hashimoto K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev. 2009;61(2):105–23. https://0-doi-org.brum.beds.ac.uk/10.1016/j.brainresrev.2009.05.005.

    Article  CAS  PubMed  Google Scholar 

  59. Giudicessi JR, Ackerman BM. 2013. 基因的改变NIH public access. Bone. 2008;23(1):1–7.

  60. 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.

  61. Diane E. Handy, Rita Castro JL. 基因的改变NIH public access. Bone. 2011;23(1):1–7.

    Google Scholar 

  62. 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://0-doi-org.brum.beds.ac.uk/10.4088/JCP.13r08898.

    Article  PubMed  Google Scholar 

  63. Kyrou I, Tsigos C. Stress hormones: physiological stress and regulation of metabolism. Curr Opin Pharmacol. 2009;9(6):787–93. https://0-doi-org.brum.beds.ac.uk/10.1016/j.coph.2009.08.007.

    Article  CAS  PubMed  Google Scholar 

  64. Wilson M, Wilson M. Men and women. Men Elders. 2018;19(2):106–41.

    Article  Google Scholar 

  65. 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://0-doi-org.brum.beds.ac.uk/10.1007/s10072-020-04444-z.

  66. 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.

  67. 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.

    Article  Google Scholar 

  68. 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.

    CAS  Google Scholar 

  69. 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://0-doi-org.brum.beds.ac.uk/10.1371/journal.pone.0153489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. 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.

    Google Scholar 

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Acknowledgements

We are grateful to all clients who participated in the study. Our sincere gratitude also goes to health workers at IDC for cooperation and assistance in recruitment and specimen collection. We thank the Centre for Research and Economic Opportunity for funding this study. We also thank the AIMS Institute and CODESRIA for providing time support to the lead author in order to perform the study. Further, we acknowledge Dr. Carol Kingori from Ohio University who participated in the protocol development and the study design, conducting a similar study in Ghana. We thank Bio-Techne for ensuring the efficient shipment of the Biomarker kits to Muhimbili Laboratory for specimen testing. Finally, the lead author acknowledges support from the National Institutes of Health R25 fellowship programs- HIV Intervention Science Training Program for Underrepresented New Investigators (HISTP program) and the Program to Increase Diversity in Behavioral Medicine and Sleep Disorders Research (PRIDE program).

Funding

The study was partially supported through funding from the Centre for Research and Economic Opportunity. The funder supported in purchase of the tests for biomarker testing.

Author information

Authors and Affiliations

  1. Division of Epidemiology and Prevention: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Room N459, Baltimore, MD, 21201, USA

    Peter Memiah

  2. Department of Medicine, University of Maryland Medical Centre Midtown Campus, Baltimore, MD, USA

    Peter Memiah

  3. Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

    Lillian Nkinda & Mtebe Majigo

  4. Global Program for Research Teaching, University of California San Francisco, Nairobi, Kenya

    Felix Humwa

  5. Department of Social Medicine, Ohio University Heritage College of Osteopathic Medicine, Dublin, OH, USA

    Zelalem T. Haile

  6. Palladium Group, Nairobi, Kenya

    Kennedy Muthoka

  7. Infectious Disease Centre, Dar es Salaam, Tanzania

    Aisha Zuheri

  8. University of Nairobi, Institute for Development Studies, Nairobi, Kenya

    Anne Kamau

  9. Institute of Primate Research, Nairobi, Kenya

    Lucy Ochola & Gabriel Buluku

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  1. Peter Memiah
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Contributions

PM conceived the study, interpreted the data, drafted the manuscript, and critically reviewed of the manuscript. PM and FH performed the analysis. AZ, LN, and MM contributed in managing the study, data collection, and critical review of the manuscript. PM helped in preparing the first draft of the manuscript. GB, AK, KM, ZH, and LN helped in critically reviewing the manuscript and meeting journal specifications. All authors participated in the critical appraisal and revision of the manuscript. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Peter Memiah.

Ethics declarations

Ethics approval and consent to participate

Approval for this study was obtained from the Muhimbili University Institutional Review Board12–06/AEC/Vol.XII/86 and the University of West Florida Institutional Review Board. Prior to enrollment in the study, participants provided a written informed consent. All ethical procedures were conducted and maintained throughout the study period.

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Not applicable

Competing interests

The authors declare that they have no competing interests.

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The original version of this article was revised as there was a spelling mistake in the given name of author Zelalem T. Haile.

The questionnaire for this study has been published in a publication [36] from the same study.

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Memiah, P., Nkinda, L., Majigo, M. et al. Mental health symptoms and inflammatory markers among HIV infected patients in Tanzania. BMC Public Health 21, 1113 (2021). https://0-doi-org.brum.beds.ac.uk/10.1186/s12889-021-11064-5

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