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Evaluating the Relationship Between Depression and Cognitive Function Among Children and Adolescents with HIV in Zambia

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Abstract

Depression is common among people living with HIV. Multiple studies demonstrate a link between depression and cognitive dysfunction in adults with HIV, but the association has been minimally investigated in children and adolescents with HIV in Africa. We conducted a cross-sectional analysis as part of the HIV-associated Neurocognitive Disorders in Zambia study, a prospective cohort study in Lusaka, Zambia. We included 208 perinatally-infected children with HIV ages 8–17 taking antiretroviral therapy and 208 HIV-exposed uninfected (HEU) controls. Cognition was assessed with a comprehensive neuropsychological battery. Depressive symptoms were evaluated using self-report and parent-report versions of the NIH Toolbox Sadness module and the Patient Health Questionnaire-9 (PHQ-9). Risk factors for depression and associations between depressive symptoms and cognition were evaluated in bivariable and multivariable regression models. Participants with HIV demonstrated higher levels of depressive symptoms than controls (mean NIH Toolbox Sadness T-Score 50 vs. 44, p < 0.01; mean PHQ-9 score 2.0 vs. 1.5, p = 0.03), and were more likely to have cognitive impairment (30% vs. 13%, p < 0.001). Risk factors for depressed mood included self-reported poor health (OR 7.8, p < 0.001) and negative life events (OR 1.3, p = 0.004) Depressed mood was associated with cognitive impairment in participants with HIV (OR = 2.9, 95% CI 1.2–7.2, p = 0.02) but not in HEU participants (OR 1.7, 95% CI 0.18–15.7, p = 0.6). In conclusion, depressed mood is common among youth with HIV in Zambia, and is associated with cognitive impairment. Depression may be a result of HIV-related stress and stigma, or may be part of the spectrum of HIV-associated neurocognitive disorders. The causal relationship between depressed mood and cognitive impairment is unclear and should be evaluated in future longitudinal studies.

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References

  1. Buch S, Chivero ET, Hoare J, et al. Proceedings from the NIMH symposium on “NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV.” J Neurovirol. 2016;22(5):699–702.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cohen S, Ter Stege JA, Geurtsen GJ, et al. Poorer cognitive performance in perinatally HIV-infected children versus healthy socioeconomically matched controls. Clin Infect Dis. 2015;60(7):1111–9.

    Article  PubMed  Google Scholar 

  3. Boivin MJ, Barlow-Mosha L, Chernoff MC, et al. Neuropsychological performance in African children with HIV enrolled in a multisite antiretroviral clinical trial. AIDS. 2018;32(2):189–204.

    Article  PubMed  Google Scholar 

  4. Wilmshurst JM, Hammond CK, Donald K, Hoare J, Cohen K, Eley B. NeuroAIDS in children. HandbClinNeurol. 2018;152:99–116.

    Google Scholar 

  5. Abubakar A. Biomedical risk, psychosocial influences, and developmental outcomes: lessons from the pediatric HIV population in Africa. New Dir Child Adolesc Dev. 2014;2014(146):23–41.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Thakur KT, Boubour A, Saylor D, Das M, Bearden DR, Birbeck GL. Global HIV neurology: a comprehensive review. AIDS. 2018;33:163.

    Article  Google Scholar 

  7. Rubin LH, Maki PM. HIV, depression, and cognitive impairment in the era of effective antiretroviral therapy. Curr HIV/AIDS Rep. 2019;16:82–95.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Carvalhal A, Baril JG, Crouzat F, et al. Recognizing cognitive and psychiatric changes in the post-highly active antiretroviral therapy era. Can J Infect Dis Med Microbiol. 2012;23:209–15.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shah S, Sinharay S, Matsuda K, et al. Potential mechanism for HIV-associated depression: upregulation of serotonin transporters in SIV-infected macaques detected by 11C-DASB PET. Front Psychiatry. 2019;10:362.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rivera-Rivera Y, Vázquez-Santiago FJ, Albino E, Sánchez MD, Rivera-Amill V. Impact of depression and inflammation on the progression of HIV disease. J Clin Cell Immunol. 2016;7:423.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Tymchuk S, Gomez D, Koenig N, Gill MJ, Fujiwara E, Power C. Associations between depressive symptomatology and neurocognitive impairment in HIV/AIDS. Can J Psychiatry. 2018;63:329–36.

    Article  PubMed  Google Scholar 

  12. Rabkin JG, Ferrando SJ, van Gorp W, Rieppi R, McElhiney M, Sewell M. Relationships among apathy, depression, and cognitive impairment in HIV/AIDS. J Neuropsychiatry ClinNeurosci. 2000;12:451–7.

    Article  CAS  Google Scholar 

  13. Saylor D, Kumar A, Nakigozi G, et al. Interleukin-6 is associated with mortality and neuropsychiatric outcomes in antiretroviral-naïve adults in Rakai, Uganda. J Neurovirol. 2019;25:735–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kalungwana L, Elafros MA, Siddiqi OK, et al. Cognitive impairment and psychiatric morbidity in HIV+ Zambians with new-onset seizure. Am J Trop Med Hyg. 2014;91(6):1254–8.

    Article  PubMed  PubMed Central  Google Scholar 

  15. McGuire JL, Kempen JH, Localio R, Ellenberg JH, Douglas SD. Immune markers predictive of neuropsychiatric symptoms in HIV-infected youth. Clin Vaccine Immunol. 2015;22:27–36.

    Article  PubMed  CAS  Google Scholar 

  16. Norcini Pala A, Steca P, Bagrodia R, et al. Subtypes of depressive symptoms and inflammatory biomarkers: an exploratory study on a sample of HIV-positive patients. Brain BehavImmun. 2016;56:105–13.

    CAS  Google Scholar 

  17. Rivera-Rivera Y, García Y, Toro V, et al. Depression correlates with increased plasma levels of inflammatory cytokines and a dysregulated oxidant/antioxidant balance in HIV-1-infected participants undergoing antiretroviral therapy. J Clin Cell Immunol. 2014;5:1000276.

    PubMed  PubMed Central  Google Scholar 

  18. Del Guerra FB, Fonseca JL, Figueiredo VM, Ziff EB, Konkiewitz EC. Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways. J Neurovirol. 2013;19(314–327):20.

    Google Scholar 

  19. Haines C, Loades ME, Coetzee BJ, Higson-Sweeney N. Which HIV-infected youth are at risk of developing depression and what treatments help? A systematic review focusing on Southern Africa. Int J Adolesc Med Health. 2019. https://doi.org/10.1515/ijamh-2019-0037.

    Article  PubMed  Google Scholar 

  20. Benton TD, Kee Ng WY, Leung D, Canetti A, Karnik N. Depression among youth living with HIV/AIDS. Child AdolescPsychiatrClin N Am. 2019;28:447–59.

    Google Scholar 

  21. Hoare J, Phillips N, Brittain K, Myer L, Zar HJ, Stein DJ. Mental health and functional competence in the Cape Town adolescent antiretroviral cohort. J Acquir Immune DeficSyndr. 2019;81:e109–16.

    Article  Google Scholar 

  22. Young-Wolff KC, Sarovar V, Sterling SA, et al. Adverse childhood experiences, mental health, substance use, and HIV-related outcomes among persons with HIV. AIDS Care. 2019;31:1241–9.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cuca YP, Shumway M, Machtinger EL, et al. The association of trauma with the physical, behavioral, and social health of women living with HIV: pathways to guide trauma-informed health care interventions. Womens Health Issues. 2019;29:376–84.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Adams HR, Mwanza-Kabaghe S, Mbewe EG, et al. The HIV-associated neurocognitive disorders in Zambia (HANDZ) study: protocol of a research program in pediatric HIV in sub-Saharan Africa. J HIV AIDS Infect Dis. 2019;5:1–18.

    Google Scholar 

  25. Nakazwe C, Michelo C, Sandøy IF, Fylkesnes K. Contrasting HIV prevalence trends among young women and men in Zambia in the past 12 years: data from demographic and health surveys 2002–2014. BMC Infect Dis. 2019;19:432.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Saito S, Chung H, Mahy M, et al. Pediatric HIV treatment gaps in 7 east and southern African countries: examination of modeled, survey, and routine program data. J Acquir Immune DeficSyndr. 2018;78(Suppl 2):S134–41.

    Article  Google Scholar 

  27. Khan S, Hancioglu A. Multiple indicator cluster surveys: delivering robust data on children and women across the globe. Stud FamPlann. 2019;50:279–86.

    Google Scholar 

  28. de Onis M, Garza C, Victora CG, Onyango AW, Frongillo EA, Martines J. The WHO Multicenter growth reference study: planning, study design and methodology. ActaPediatSupp. 2006;447:12–24.

    Google Scholar 

  29. Carey CL, Woods SP, Gonzalez R, et al. Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J ClinExpNeuropsychol. 2004;26:307–19.

    Google Scholar 

  30. Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789–99.

    Article  CAS  PubMed  Google Scholar 

  31. Salsman JM, Butt Z, Pilkonis PA, et al. Emotion assessment using the NIH Toolbox. Neurology. 2013;80:S76-86.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Paolillo EW, McKenna BS, Nowinski CJ, Thomas ML, Malcarne VL, Heaton RK. NIH Toolbox® emotion batteries for children: factor-based composites and norms. Assessment. 2018. https://doi.org/10.1177/1073191118766396.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Babakhanyan I, McKenna BS, Casaletto KB, Nowinski CJ, Heaton RK. National Institutes of Health Toolbox Emotion Battery for English- and Spanish-speaking adults: normative data and factor-based summary scores. Patient Relat Outcome Meas. 2018;9:115–27.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kabundelo P, Mbewe M, Mwanza-Kabaghe S, Adams H, Bearden DR (2018) Validation of the NIH toolbox, an iPad-based test of cognition, in children and adolescents in Zambia. Abstract, Evidence for Impact Conference. Lusaka, Zambia

  35. Allgaier AK, Pietsch K, Frühe B, Sigl-Glöckner J, Schulte-Körne G. Screening for depression in adolescents: validity of the patient health questionnaire in pediatric care. Depress Anxiety. 2012;29:906–13.

    Article  PubMed  Google Scholar 

  36. Royston P, Sauerbrei W. Multivariable model-building: a pragmatic approachto regression analysis based on fractional polynomials for continuous variables. Ch. 9.3. Chichester: Wiley; 2008. p. 203–5.

    Book  Google Scholar 

  37. Musinguzi K, Obuku A, Nakasujja N, et al. Association between major depressive disorder and pro-inflammatory cytokines and acute phase proteins among HIV-1 positive patients in Uganda. BMC Immunol. 2018;19:1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Beumer W, Gibney SM, Drexhage RC, et al. The immune theory of psychiatric diseases: a key role for activated microglia and circulating monocytes. J LeukocBiol. 2012;92:959–75.

    Article  CAS  Google Scholar 

  39. Chiang JJ, Cole SW, Bower JE, et al. Depressive symptoms and immune transcriptional profiles in late adolescents. Brain BehavImmun. 2019;80:163–9.

    CAS  Google Scholar 

  40. Ferrari P, Parisi MM, Colombo R, et al. Depression and mania induce pro-inflammatory activation of macrophages following application of serum from individuals with bipolar disorder. ClinPsychopharmacolNeurosci. 2018;16:103–8.

    CAS  Google Scholar 

  41. Grosse L, Carvalho LA, Wijkhuijs AJ, et al. Clinical characteristics of inflammation-associated depression: monocyte gene expression is age-related in major depressive disorder. Brain Behav Immun. 2015;44:48–56.

    Article  CAS  PubMed  Google Scholar 

  42. Grosse L, Hoogenboezem T, Ambrée O, et al. Deficiencies of the T and natural killer cell system in major depressive disorder: T regulatory cell defects are associated with inflammatory monocyte activation. Brain BehavImmun. 2016;54:38–44.

    CAS  Google Scholar 

  43. Johnson JD, Barnard DF, Kulp AC, Mehta DM. Neuroendocrine regulation of brain cytokines after psychological stress. J Endocr Soc. 2019;3:1302–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kim YK, Na KS, Shin KH, Jung HY, Choi SH, Kim JB. Cytokine imbalance in the pathophysiology of major depressive disorder. ProgNeuropsychopharmacolBiol Psychiatry. 2007;31:1044–53.

    Article  CAS  Google Scholar 

  45. Liberman AC, Trias E, da Silva CL, et al. Neuroimmune and inflammatory signals in complex disorders of the central nervous system. NeuroImmunoModulation. 2018;25:246–70.

    Article  CAS  PubMed  Google Scholar 

  46. Lisi L, Camardese G, Treglia M, et al. Monocytes from depressed patients display an altered pattern of response to endotoxin challenge. PLoS ONE. 2013;8:e52585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mazza MG, Lucchi S, Tringali AGM, Rossetti A, Botti ER, Clerici M. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: a meta-analysis. ProgNeuropsychopharmacolBiol Psychiatry. 2018;84:229–36.

    Article  Google Scholar 

  48. McKim DB, Weber MD, Niraula A, et al. Microglial recruitment of IL-1β-producing monocytes to brain endothelium causes stress-induced anxiety. Mol Psychiatry. 2018;23:1421–31.

    Article  CAS  PubMed  Google Scholar 

  49. Miklowitz DJ, Portnoff LC, Armstrong CC, et al. Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders. Psychiatry Res. 2016;241:315–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Demoze MB, Angaw DA, Mulat H. Prevalence and associated factors of depression among orphan adolescents in Addis Ababa, Ethiopia. Psychiatry J. 2018;2018:5025143.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kumar SP, Dandona R, Kumar GA, Ramgopal S, Dandona L. Depression among AIDS-orphaned children higher than among other orphaned children in southern India. Int J Ment Health Syst. 2014;8:13.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Shiferaw G, Bacha L, Tsegaye D. Prevalence of depression and its associated factors among orphan children in orphanages in Ilu Abba Bor zone. South West Ethiopia Psychiatry J. 2018;2018:6865085.

    PubMed  Google Scholar 

  53. Lackey GF. “Feeling blue” in Spanish: a qualitative inquiry of depression among Mexican immigrants. SocSci Med. 2008;67:228–37.

    Article  Google Scholar 

  54. Brown AD, Mentha R, Rowley KG, Skinner T, Davy C, O’Dea K. Depression in Aboriginal men in central Australia: adaptation of the Patient Health Questionnaire 9. BMC Psychiatry. 2013;13:271.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Bröer C, Besseling B. Sadness or depression: making sense of low mood and the medicalization of everyday life. SocSci Med. 2017;183:28–36.

    Article  Google Scholar 

  56. Bolton P. Cross-cultural validity and reliability testing of a standard psychiatric assessment instrument without a gold standard. J NervMent Dis. 2001;189:238–42.

    Article  CAS  Google Scholar 

  57. Lee B, Kaaya SF, Mbwambo JK, Smith-Fawzi MC, Leshabari MT. Detecting depressive disorder with the Hopkins Symptom Checklist-25 in Tanzania. Int J Soc Psychiatry. 2008;54:7–20.

    Article  PubMed  Google Scholar 

  58. Mendenhall E, Rinehart R, Musyimi C, Bosire E, Ndetei D, Mutiso V. An ethnopsychology of idioms of distress in urban Kenya. Transcult Psychiatry. 2019;56:620–42.

    Article  PubMed  Google Scholar 

  59. Omoro SA, Fann JR, Weymuller EA, Macharia IM, Yueh B. Swahili translation and validation of the Patient Health Questionnaire-9 depression scale in the Kenyan head and neck cancer patient population. Int J Psychiatry Med. 2006;36:367–81.

    Article  CAS  PubMed  Google Scholar 

  60. Tsai AC, Scott JA, Hung KJ, et al. Reliability and validity of instruments for assessing perinatal depression in African settings: systematic review and meta-analysis. PLoS ONE. 2013;8:e82521.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

This work was supported by the University of Rochester Center for AIDS Research (CFAR), an NIH funded program (P30 AI 045008); the McGowan Foundation; and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01NS094037 and K23NS117310. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Johns Hopkins School of Medicine, Baltimore, MD, USA

    Maria Molinaro

  2. Division of Child Neurology, Department of Neurology, University of Rochester School of Medicine, 601 Elmwood Ave, Box 631, Rochester, NY, 14642, USA

    Heather R. Adams & David R. Bearden

  3. Department of Educational Psychology, University of Zambia, Lusaka, Zambia

    Sylvia Mwanza-Kabaghe, Esau G. Mbewe, Pelekelo P. Kabundula & David R. Bearden

  4. University Teaching Hospital Neurology Research Office, Lusaka, Zambia

    Milimo Mweemba

  5. Division of Epilepsy, Department of Neurology, Rochester, NY, USA

    Gretchen L. Birbeck

  6. University of Zambia School of Medicine, Lusaka, Zambia

    Gretchen L. Birbeck

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  1. Maria Molinaro
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  2. Heather R. Adams
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  3. Sylvia Mwanza-Kabaghe
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Contributions

MM: assisted in conceptualizing and designing the study, collected data, carried out data analysis, drafted and revised the manuscript, and approved the final manuscript as submitted. DRB: conceptualized and designed the study, collected data, carried out data analysis, assisted in drafting and revising the manuscript, and approved the final manuscript as submitted. All other authors assisted in conceptualizing and designing the study, collected data or advised on the process of data collection, assisted in drafting and revising the manuscript, and approved the final manuscript as submitted.

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Correspondence to David R. Bearden.

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Molinaro, M., Adams, H.R., Mwanza-Kabaghe, S. et al. Evaluating the Relationship Between Depression and Cognitive Function Among Children and Adolescents with HIV in Zambia. AIDS Behav 25, 2669–2679 (2021). https://doi.org/10.1007/s10461-021-03193-0

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