Top

Published in:

01-02-2021 | Affective Disorder

Brain-derived neurotrophic factor (BDNF) is associated with depressive symptoms in older adults with HIV disease

Authors: Steven Paul Woods, Michelle Babicz, Lokesh Shahani, Gabriela Delevati Colpo, Erin E. Morgan, Antonio L. Teixeira

Published in: Journal of NeuroVirology | Issue 1/2021

Abstract

Symptoms of depression are common among persons with HIV (PWH) and can have a significant impact on socioeconomic and personal well-being, but little is known about their neurobiological substrates in the context of HIV disease. This study examined the possible role of brain-derived neurotrophic factor (BDNF) in symptoms of depression and other aspects of mood in 109 PWH and 43 seronegative participants aged 50 and older. Participants completed the Profile of Mood States (POMS) which measured six dimensions of mood and was normatively adjusted for sex. A model controlling for medical comorbidities and substance use diagnoses among PWH showed a significant interaction between BDNF and POMS subscales. Planned post hoc analyses revealed that lower BDNF was only associated with higher scores on Depression-Dejection and Confusion-Bewilderment POMS subscales among PWH and at small-to-medium effect sizes. Lower levels of BDNF were associated with AIDS diagnoses and CD4 count, but not with viremia or duration of infection. BDNF levels did not differ between the PWH and HIV − samples, and there were no significant correlations between BDNF and any POMS variable in the HIV − group. Findings implicate BDNF in the neuropathophysiology of specific depressive symptoms in the context of HIV disease. Future studies may examine whether BDNF levels change over time, are sensitive to other aspects of mood disorders in HIV, and are associated with markers of HIV-associated neural injury.

Aljassem K, Raboud JM, Hart TA et al (2016) Gender differences in severity and correlates of depression symptoms in people living with HIV in Ontario, Canada. J Int Assoc Provid AIDS Care 15(1):23–35. https://doi.org/10.1177/2325957414536228CrossRefPubMed

Alterman AI, Tarter RE (1985) Assessing the influence of confounding subject variables in neuropsychological research in alcoholism and related disorders. Int J Neurosci 26(1–2):75–84. https://doi.org/10.3109/00207458508985606CrossRefPubMed

Amare T, Getinet W, Shumet S, Asrat B (2018) Prevalence and associated factors of depression among PLHIV in Ethiopia: systematic review and meta-analysis, 2017. AIDS Res Treat 2018:5462959. https://doi.org/10.1155/2018/5462959CrossRefPubMedPubMedCentral

American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (5^th ed.). Washington, DC.

Armstrong G, Jorm AF, Samson L, Joubert L, Nuken A, Singh S, Kermode M (2013) Association of depression, anxiety, and suicidal ideation with high-risk behaviors among men who inject drugs in Delhi. India J Acquir Immune Defic Syndr 64(5):502–510. https://doi.org/10.1097/QAI.0b013e3182a7ef21CrossRefPubMed

Arseniou S, Arvaniti A, Samakouri M (2014) HIV infection and depression. Psychiatry Clin Neurosci 68(2):96–109. https://doi.org/10.1111/pcn.12097CrossRefPubMed

Asrat B, Schneider M, Ambaw F, Lund C (2020) Effectiveness of psychological treatments for depressive symptoms among people living with HIV/AIDS in low- and middle-income countries: a systematic review and meta-analysis. J Affect Disord 270:174–187. https://doi.org/10.1016/j.jad.2020.03.068CrossRefPubMed

Avdoshina V, Garzino-Demo A, Bachis A, Monaco MC, Maki PM, Tractenberg RE, Liu C, Young MA, Mocchetti I (2011) HIV-1 decreases the levels of neurotrophins in human lymphocytes. AIDS 25(8):1126–1128. https://doi.org/10.1097/QAD.0b013e32834671b3CrossRefPubMedPubMedCentral

Avdoshina V, Mocchetti I, Liu C, Young MA, Anastos K, Cohen M, Crystal H, Pearce CL, Golub ET, Tractenberg RE (2013) Single-nucleotide polymorphisms in TrkB and risk for depression: findings from the women’s interagency HIV study. J Acquir Immune Defic Syndr 64(2):138–141. https://doi.org/10.1097/QAI.0b013e3182a468e9CrossRefPubMedPubMedCentral

Babicz M, Woods SP, Morgan EE, Fazeli P (in press). Apathy is associated with critical psychological determinants of medication adherence in HIV disease. J Clin Psychol Med Settings.doi: https://doi.org/10.1007/s10880-020-09715-7

Bachis A, Avdoshina V, Zecca L, Parsadanian M, Mocchetti I (2012) Human immunodeficiency virus type 1 alters brain-derived neurotrophic factor processing in neurons. J Neurosci 32(28):9477–9484. https://doi.org/10.1523/JNEUROSCI.0865-12.2012CrossRefPubMedPubMedCentral

Brunoni AR, Lopes M, Fregni F (2008) A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 11(8):1169–1180. https://doi.org/10.1017/S1461145708009309CrossRefPubMed

Carboni L, McCarthy DJ, Delafont B, Filosi M, Ivanchenko E, Ratti E, Learned SM, Alexander R, Domenici E (2019) Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies. Transl Psychiatry 9(1):182. https://doi.org/10.1038/s41398-019-0521-7CrossRefPubMedPubMedCentral

Chichetto NE, Polanka BM, So-Armah KA et al (2020) Contribution of behavioral health factors to non-AIDS-related comorbidities: an updated review. Curr HIV/AIDS Rep. https://doi.org/10.1007/s11904-020-00498-y.10.1007/s11904-020-00498-yCrossRefPubMed

Ciesla JA, Roberts JE (2001) Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry 158(5):725–730. https://doi.org/10.1176/appi.ajp.158.5.725CrossRefPubMed

Colpo GD, Leboyer M, Dantzer R, Trivedi MH, Teixeira AL (2018) Immune-based strategies for mood disorders: facts and challenges. Expert Rev Neurother 18(2):139–152. https://doi.org/10.1080/14737175.2018.1407242CrossRefPubMed

Composite International Diagnostic Interview (CIDI): Core Version 2.1 (1998) World Health Organization.

Cysique LA, Brew BJ (2019) Comorbid depression and apathy in HIV-associated neurocognitive disorders in the era of chronic HIV infection. Handb Clin Neurol 165:71–82. https://doi.org/10.1016/B978-0-444-64012-3.00006-XCrossRefPubMed

Del Guerra FB, Fonseca JL, Figueiredo VM, Ziff EB, Konkiewitz EC (2013) Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways. J Neurovirol 19(4):314–327. https://doi.org/10.1007/s13365-013-0177-7CrossRefPubMed

Ferreira AC, Teixeira AL, Silveira MF, Carneiro M (2018) Quality of life predictors for people living with HIV/AIDS in an impoverished region of Brazil. Rev Soc Bras Med Trop 51(6):743–751. https://doi.org/10.1590/0037-8682-0442-2017CrossRefPubMed

Gonzalez JS, Batchelder AW, Psaros C, Safren SA (2011) Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr 58(2):181–187. https://doi.org/10.1097/QAI.0b013e31822d490aCrossRefPubMed

Heaton RK, Marcotte TD, Mindt MR, Sadek J, Moore DJ, Bentley H, McCutchan JA, Reicks C, Grant I, HNRC Group (2004) The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc 10(3):317–331. https://doi.org/10.1017/S1355617704102130CrossRefPubMed

JMP®, Version 14.0.0. SAS Institute Inc., Cary, NC, 1989–2020

Kamat R, Woods SP, Cameron MV, Iudicello JE, The HNRP Group (2016) Apathy is associated with lower physical and mental health-related quality of life in HIV disease. Psychol Health Med 21(7):890–901. https://doi.org/10.1080/13548506.2015.1131998CrossRef

Kalichman SC, Rompa D, Cage M (2000) Distinguishing between overlapping somatic symptoms of depression and HIV disease in people living with HIV-AIDS. J Nerv Ment Dis 188(10):662–670. https://doi.org/10.1097/00005053-200010000-00004CrossRefPubMed

Katon W, Ciechanowski P (2002) Impact of major depression on chronic medical illness. J Psychosom Res 53(4):859–863. https://doi.org/10.1016/s0022-3999(02)00313-6CrossRefPubMed

Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M, Knudsen GM, Aznar S (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14(3):347–353. https://doi.org/10.1017/S1461145710000738CrossRefPubMed

Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N, Herrmann N, Raison CL, Miller BJ, Lanctôt KL, Carvalho AF (2017) Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand 135(5):373–387. https://doi.org/10.1111/acps.12698CrossRefPubMed

Levine AJ, Sinsheimer JS, Bilder R, Shapshak P, Singer EJ (2012) Functional polymorphisms in dopamine-related genes: effect on neurocognitive functioning in HIV+ adults. J Clin Exp Neuropsychol 34(1):78–91. https://doi.org/10.1080/13803395.2011.623118CrossRefPubMed

Levy MJF, Boulle F, Steinbusch HW, van de Hove DLA, Kenis G, Lanfumey L (2018) Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression. Psychopharmacology 235:2195–2220. https://doi.org/10.1007/s00213-018-4950-4CrossRefPubMedPubMedCentral

Lorenzetti V, Costafreda SG, Rimmer RM, Rasenick MM, Marangell LB, Fu CHY (2020) Brain-derived neurotrophic factor association with amygdala response in major depressive disorder. J Affect Disord 267:103–106. https://doi.org/10.1016/j.jad.2020.01.159CrossRefPubMed

Luan S, Zhou B, Wu Q, Wan H, Li H (2020) Brain-derived neurotrophic factor blood levels after electroconvulsive therapy in patients with major depressive disorder: a systematic review and meta-analysis. Asian J Psychiatr 51:101983. https://doi.org/10.1016/j.ajp.2020.101983CrossRefPubMed

Malhi GS, Mann JJ (2018) Depression. Lancet 392(10161):2299–2312. https://doi.org/10.1016/S0140-6736(18)31948-2CrossRefPubMed

McNair DM, Lorr M, Droppleman LF (1981) Profile of mood states. Educational and Industrial Testing Service, San Diego, CA

Míguez-Burbano MJ, Espinoza L, Cook RL, Mayra M, Bueno D, Lewis JE, Asthana D (2013) Alcohol, brain derived neurotrophic factor and obesity among people living with HIV. J AIDS Clin Res 4:245. https://doi.org/10.4172/2155-6113.1000245CrossRefPubMedPubMedCentral

Míguez-Burbano MJ, Espinoza L, Vargas M, LaForest D (2014) Mood disorders and BDNF relationship with alcohol drinking trajectories among PLWH receiving care. J Alcohol Drug Depend 2(2):148. https://doi.org/10.4172/2329-6488.100148CrossRefPubMedPubMedCentral

Míguez-Burbano MJ, Espinoza L, Whitehead NE, Bryant VE, Vargas M, Cook RL, Quiros C, Lewis JE, Deshratan A (2014) Brain derived neurotrophic factor and cognitive status: the delicate balance among people living with HIV, with and without alcohol abuse. Curr HIV Res 12(4):254–264. https://doi.org/10.2174/1570162x12666140721121238CrossRefPubMedPubMedCentral

Mocchetti I, Bachis A, Campbell LA, Avdoshina V (2014) Implementing neuronal plasticity in NeuroAIDS: the experience of brain-derived neurotrophic factor and other neurotrophic factors. J Neuroimmune Pharmacol 9(2):80–91. https://doi.org/10.1007/s11481-013-9488-yCrossRefPubMed

Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM (2014) Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484). Mol Psychiatry 19(7):791–800. https://doi.org/10.1038/mp.2013.105CrossRefPubMed

Mourão AM, Vicente LCC, Abreu MNS, Vale Sant’Anna R, Vieira ELM, de Souza LC, de Miranda AS, Rachid MA, Teixeira AL (2019) Plasma levels of brain-derived neurotrophic factor are associated with prognosis in the acute phase of ischemic stroke. J Stroke Cerebrovasc Dis 28(3):735–740. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.11.013CrossRefPubMed

Nanni MG, Caruso R, Mitchell AJ, Meggiolaro E, Grassi L (2015) Depression in HIV infected patients: a review. Curr Psychiatry Rep 17(1):530. https://doi.org/10.1007/s11920-014-0530-4CrossRefPubMed

Nosheny RL, Bachis A, Acquas E, Mocchetti I (2004) Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of brain-derived neurotrophic factor in vivo: potential implication for neuronal cell death. Eur J Neurosci 20(11):2857–2864. https://doi.org/10.1111/j.1460-9568.2004.03764.xCrossRefPubMed

Nyenhuis DL, Yamamoto C, Luchetta T, Terrien A, Parmentier A (1999) Adult and geriatric normative data and validation of the Profile of Mood States. J Clin Psychol. 55: 79–86. doi:

1002/(sici)1097–4679(199901)55:1<79::aid-jclp8>3.0.co;2–7

Palin K, McCusker RH, Strle K, Moos F, Dantzer R, Kelley KW (2008) Tumor necrosis factor-alpha-induced sickness behavior is impaired by central administration of an inhibitor of c-jun N-terminal kinase. Psychopharmacology 197(4):629–635. https://doi.org/10.1007/s00213-008-1086-yCrossRefPubMedPubMedCentral

Pandey GN, Ren X, Rizavi HS, Conley RR, Roberts RC, Dwivedi Y (2008) Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol 11(8):1047–1061. https://doi.org/10.1017/S1461145708009000CrossRefPubMed

Patterson K, Young C, Woods SP, Vigil O, Grant I, Atkinson JH; HIV Neurobehavioral Research Center Group (2006) Screening for major depression in persons with HIV infection: the concurrent predictive validity of the Profile of Mood States Depression-Dejection Scale. Int J Methods Psychiatr Res 15(2):75–82. https://doi.org/10.1002/mpr.184CrossRef

Rabkin JG (2008) HIV and depression: 2008 review and update. Curr HIV/AIDS Rep 5(4):163–171. https://doi.org/10.1007/s11904-008-0025-1CrossRefPubMed

Rahmani F, Saghazadeh A, Rahmani M, Teixeira AL, Rezaei N, Aghamollaii V, Ardebili HE (2019) Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: a systematic review and meta-analysis. Brain Res 1704:127–136. https://doi.org/10.1016/j.brainres.2018.10.006CrossRefPubMed

Remien RH, Stirratt MJ, Nguyen N, Robbins RN, Pala AN, Mellins CA (2019) Mental health and HIV/AIDS: the need for an integrated response. AIDS 33(9):1411–1420. https://doi.org/10.1097/QAD.0000000000002227CrossRefPubMedPubMedCentral

Rooney AS, Moore RC, Paolillo EW et al (2019) Depression and aging with HIV: associations with health-related quality of life and positive psychological factors. J Affect Disord 251:1–7. https://doi.org/10.1016/j.jad.2019.03.025CrossRefPubMedPubMedCentral

Sherr L, Clucas C, Harding R, Sibley E, Catalan J (2011) HIV and depression: a systematic review of interventions. Psychol Health Med 16(5):493–527. https://doi.org/10.1080/13548506.2011.579990CrossRefPubMed

Snider WD, Simpson DM, Nielsen S, Gold JW, Metroka CE, Posner JB (1983) Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol 14(4):403–418. https://doi.org/10.1002/ana.410140404CrossRefPubMed

So-Armah K, Gupta SK, Kundu S, Stewart JC, Goulet JL, Butt AA, Sico JJ, Marconi VC, Crystal S, Rodriguez-Barradas MC, Budoff M, Gibert CL, Chang CC, Bedimo R, Freiberg MS (2019) Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study. HIV Med 20(5):317–329. https://doi.org/10.1111/hiv.12726CrossRefPubMedPubMedCentral

Teixeira AL, Barbosa IG, Diniz BS, Kummer A (2010) Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function. Biomark Med 4(6):871–887. https://doi.org/10.2217/bmm.10.111CrossRefPubMed

Teixeira AL, Colpo GD, Fries GR, Bauer IE, Selvaraj S (2019) Biomarkers for bipolar disorder: current status and challenges ahead. Expert Rev Neurother 19(1):67–81. https://doi.org/10.1080/14737175.2019.1550361CrossRefPubMed

Weber E, Morgan EE, Iudicello JE, Blackstone K, Grant I, Ellis RJ, Letendre SL, Little S, Morris S, Smith DM, Moore DJ, Woods SP, TMARC Group (2013) Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection. J Neurovirol 19(1):65–74. https://doi.org/10.1007/s13365-012-0141-yCrossRefPubMed

Wilhelm CJ, Fuller BE, Huckans M, Loftis JM (2017) Peripheral immune factors are elevated in women with current or recent alcohol dependence and associated with altered mood and memory. Drug Alcohol Depend 176:71–78. https://doi.org/10.1016/j.drugalcdep.2017.02.023CrossRefPubMedPubMedCentral

Woods SP, Carey CL, Moran LM, Dawson MS, Letendre SL, Grant I, HIV Neurobehavioral Research Center (HNRC) Group (2007) Frequency and predictors of self-reported prospective memory complaints in individuals infected with HIV. Arch Clin Neuropsychol 22(2):187–195. https://doi.org/10.1016/j.acn.2006.12.006CrossRefPubMedPubMedCentral

Woods SP, Morgan EE, Loft S, Matchanova AM, Verduzco M, Cushman C (2020) Supporting strategic processing can improve time-based prospective memory in the laboratory among older adults with HIV disease. Neuropsychology 34:249–263. https://doi.org/10.1037/neu0000602CrossRefPubMed

Youssef MM, Underwood MD, Huang YY, Hsiung SC, Liu Y, Simpson NR, Bakalian MJ, Rosoklija GB, Dwork AJ, Arango V, Mann JJ (2018) Association of BDNF Val66Met polymorphism and brain BDNF levels with major depression and suicide. Int J Neuropsychopharmacol 21:528–538. https://doi.org/10.1093/ijnp/pyy008CrossRefPubMedPubMedCentral

Zhang HF, Mellor D, Peng DH (2018) Neuroimaging genomic studies in major depressive disorder: a systematic review CNS Neurosci Ther 24(11):1020–1036. https://doi.org/10.1111/cns.12829CrossRefPubMed

Zihao L, Purcell DW, Sansom SL, Hayes D, Hall I (2019) Vital signs: HIV transmission along the continuum of care – United States 2016. MMWR Morb Mortal Wkly Rep 68(11):267–272. https://doi.org/10.15585/mmwr.mm6811e1CrossRef

Zuniga JA, Yoo-Jeong M, Dai T, Guo Y, Waldrop-Valverde D (2016) The role of depression in retention in care for persons living with HIV. AIDS Patient Care STDS 30(1):34–38. https://doi.org/10.1089/apc.2015.0214CrossRefPubMedPubMedCentral

Title: Brain-derived neurotrophic factor (BDNF) is associated with depressive symptoms in older adults with HIV disease
Authors: Steven Paul Woods
Michelle Babicz
Lokesh Shahani
Gabriela Delevati Colpo
Erin E. Morgan
Antonio L. Teixeira
Publication date: 01-02-2021
Publisher: Springer International Publishing
Keywords: Affective Disorder
Human Immunodeficiency Virus
Affective Disorder
Acquired Immune Deficiency Syndrome
Biomarkers
Published in: Journal of NeuroVirology / Issue 1/2021
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-020-00916-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Brain-derived neurotrophic factor (BDNF) is associated with depressive symptoms in older adults with HIV disease

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2021

Potential mechanisms of cerebrovascular diseases in COVID-19 patients

Predictive factors of human cytomegalovirus reactivation in newly diagnosed glioblastoma patients treated with chemoradiotherapy

Machine learning prediction of neurocognitive impairment among people with HIV using clinical and multimodal magnetic resonance imaging data

Brain tissue transcriptomic analysis of SIV-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (ADP-ribose) polymerases (PARPs) as potential therapeutic targets

Chronically elevated depressive symptoms interact with acute increases in inflammation to predict worse neurocognition among people with HIV

Imaging manifestations on sequential magnetic resonance imaging in pharyngolaryngeal involvement by varicella zoster virus