Skip to main content

Advertisement

SpringerLink
Log in

Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways

  • Review
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

In the era of greatly improved pharmacological treatment of HIV infection through highly active antiretroviral therapy (HAART), HIV patients experience reduced viral loads, reduced opportunistic infections, increased CD4+ T cell count, and greater life expectancy. Although life expectancy is increased, patients often develop neurological disturbances that may persist for long periods, seriously jeopardizing quality of life and adherence to the medication protocols of HAART. For these reasons, HIV-associated neurological disorders have gained importance in both clinical and basic investigations of HIV infection. Depression is the most prevalent neuropsychiatric disorder among people living with HIV. In this review, we discuss how HIV can predispose infected individuals to depression by several interrelated mechanisms. These include inducing chronic elevation of cytokines through activation of microglia and astrocytes; decreasing monoaminergic function; inducing neurotoxicity, especially in dopaminergic neurons; and reducing brain-derived neurotrophic factor. These viral pathways interact with psychosocial factors to create the depressive state. HIV depression has a great impact on quality of life and implementation of antiretroviral therapy, and thus, recognition of these modes of action is significant for understanding HIV neuropathology and for selecting modalities for pharmacologic treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Albini A, Soldi R, Giunciuglio D, Giraudo E, Benelli R, Primo L, Noonan D, Salio M, Camussi G, Rockl W, Bussolino F (1996) The angiogenesis induced by HIV-1 Tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells. Nat Med 2(12):1371–1375

    Article  PubMed  CAS  Google Scholar 

  • Al-shair K, Kolsum U, Dockry R, Morris J, Singh D, Vestbo J (2011) Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD. Respir Res 12(1):3

    Article  PubMed  Google Scholar 

  • Aprea S, Del Valle L, Mameli G, Sawaya BE, Khalili K, Peruzzi F (2006) Tubulin-mediated binding of human immunodeficiency virus-1 Tat to the cytoskeleton causes proteasomal-dependent degradation of microtubule-associated protein 2 and neuronal damage. J Neurosci 26(15):4054–4062

    Article  PubMed  CAS  Google Scholar 

  • Bachis A, Major EO, Mocchetti I (2003) Brain-derived neurotrophic factor inhibits human immunodeficiency virus-1/gp120-mediated cerebellar granule cell death by preventing gp120 internalization. J Neurosci 23(13):5715–5722

    PubMed  CAS  Google Scholar 

  • Banisadr G, Fontanges P, Haour F, Kitabgi P, Rostène W, Mélik Parsadaniantz S (2002) Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons. Eur J Neurosci 16(9):1661–1671

    Article  PubMed  Google Scholar 

  • Bansal AK, Mactutus CF, Nath A, Maragos W, Hauser KF, Booze RM (2000) Neurotoxicity of HIV-1 proteins gp120 and Tat in the rat striatum. Brain Res 879(1–2):42–49

    Article  PubMed  CAS  Google Scholar 

  • Bennett BA, Rusyniak DE, Hollingsworth CK (1995) HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures. Brain Res 705(1–2):168–176

    Article  PubMed  CAS  Google Scholar 

  • Berger JR, Kumar M, Kumar A, Fernandez JB, Levin B (1994) Cerebrospinal fluid dopamine in HIV-1 infection. AIDS 8:67–71

    Article  PubMed  CAS  Google Scholar 

  • Bragança M, Palha A (2011) Depression and neurocognitive performance in Portuguese patients infected with HIV. AIDS Behav 15(8):1879–1887

    Article  PubMed  Google Scholar 

  • Brenu EW, van Driel ML, Staines DR, Ashton KJ, Ramos SB, Keane J, Klimas NG, Marshall-Gradisnik SM (2011) Immunological abnormalities as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med 9:81

    Article  PubMed  CAS  Google Scholar 

  • Brydon L, Harrison NA, Walker C, Steptoe A, Critchley HD (2008) Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry 63(11):1022–1029

    Article  PubMed  CAS  Google Scholar 

  • Buescher JL, Gross S, Gendelman HE, Ikezu T (2007) The neuropathogenesis of HIV-1 infection. Handbook of Clinical Neurology 85:45–67

    Article  PubMed  Google Scholar 

  • Capuron L, Pagnoni G, Demetrashvili MF, Lawson DH, Fornwalt FB, Woolwine B, Berns GS, Nemeroff CB, Miller AH (2007) Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology 32(11):2384–2392

    Article  PubMed  CAS  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    Article  PubMed  CAS  Google Scholar 

  • Castellon SA, Hardy DJ, Hinkin CH, Satz P, Stenquist PK, van Gorp WG, Myers HF, Moore L (2006) Components of depression in HIV-1 infection: their differential relationship to neurocognitive performance. J Clin Exp Neuropsychol 28(3):420–437

    Article  PubMed  Google Scholar 

  • Cavanagh J, Paterson C, McLean J, Pimlott S, McDonald M, Patterson J, Wyper D, McInnes I (2010) Tumour necrosis factor blockade mediates altered serotonin transporter availability in rheumatoid arthritis: a clinical, proof-of-concept study. Ann Rheum Dis 69:1251–1252

    Article  PubMed  Google Scholar 

  • Corasaniti MT, Piccirilli S, Paoletti A, Nisticò R, Stringaro A, Malorni W, Finazzi-Agrò A, Bagetta G (2001) Evidence that the HIV-1 coat protein gp120 causes neuronal apoptosis in the neocortex of rat via a mechanism involving CXCR4 chemokine receptor. Neurosci Lett 312:67–70

    Article  PubMed  CAS  Google Scholar 

  • Cozzi-Lepri A, French MA, Baxter J, Okhuysen P, Plana M, Neuhaus J, Landay A, INSIGHT SMART study group (2011) Resumption of HIV replication is associated with monocyte/macrophage derived cytokine and chemokine changes: results from a large international clinical trial. AIDS 25(9):1207–1217

    Article  PubMed  CAS  Google Scholar 

  • Cysique LA, Deutsch R, Atkinson JH, Young C, Marcotte TD, Dawson L, Grant I, Heaton RK, The HNRC Group (2007) Incident major depression does not affect neuropsychological functioning in HIV-infected men. J Int Neuropsychol Soc 13:1–11

    Article  PubMed  Google Scholar 

  • Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56

    Article  PubMed  CAS  Google Scholar 

  • Ensoli B, Buonaguro L, Barillari G, Fiorelli V, Gendelman R, Morgan RA, Wingfeld P, Gallo RC (1993) Release, uptake and effects of extracellular human immunodeficiency virus type I Tat protein on cell growth and viral transactivation. J Virol 67:277–287

    PubMed  CAS  Google Scholar 

  • Eugenin EA, D’Aversa TG, Lopez L, Calderon TM, Berman JW (2003) MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. J Neurochem 85:1299–1311

    Article  PubMed  CAS  Google Scholar 

  • Everall IP, Luthert PJ, Lantos PL (1993) Neuronal number and volume alterations in the neocortex of HIV infected individuals. J Neurol Neurosurg Psychiatry 56(5):481–486

    Article  PubMed  CAS  Google Scholar 

  • Fernandes Filho SM, de Melo HR (2012) Frequency and risk factors for HIV-associated neurocognitive disorder and depression in older individuals with HIV in northeastern Brazil. Int Psychogeriatr 22:1–8

    Google Scholar 

  • Fischer-Smith T, Rappaport J (2005) Evolving paradigms in the pathogenesis of HIV-1-associated dementia. Expert Rev Mol Med 7(27):1–26, http://www.expertreviews.org/

    Article  PubMed  Google Scholar 

  • Fitting S, Booze RM, Mactutus CF (2006) Neonatal intrahippocampal glycoprotein 120 injection: the role of dopaminergic alterations in prepulse inhibition in adult rats. JPET 318:1352–1358

    Article  CAS  Google Scholar 

  • Fujise N, Ikeda M (2012) The relationship between depression and dementia in elderly. Seishin Shinkeigaku Zasshi 114(3):276–282

    PubMed  Google Scholar 

  • Gaskill PJ, Calderon TM, Luers AJ, Eugenin EA, Javitch JA, Berman JW (2009) Human immunodeficiency virus (HIV) infection of human macrophages is increased by dopamine a bridge between HIV-associated neurologic disorders and drug abuse. Am J Pathol 175:3

    Article  Google Scholar 

  • Gendelman HE, Lipton SA, Tardieu M, Bukrinsky MI, Nottet HSLM (1994) The neuropathogenesis of HIV-1 infection. J Leukoc Biol 56:389–398

    PubMed  CAS  Google Scholar 

  • Ghezzi S, Noonan DM, Aluigi MG, Vallanti G, Cota M, Benelli R, Morini M, Reeves JD, Vicenzi E, Poli G, Albini A (2000) Inhibition of CXCR4-dependent HIV-1 infection by extracellular HIV-1 Tat. Biochem Biophys Res Commun 270(3):992–996

    Article  PubMed  CAS  Google Scholar 

  • Gibbie T, Mijch A, Ellen S, Hoy J, Hutchison C, Wright E, Chua P, Judd F (2006) Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up. HIV Medicine 7(2):112–121

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez A, Solomon SE, Zvolensky MJ, Miller CT (2009) The interaction of mindful-based attention and awareness and disengagement coping with HIV/AIDS-related stigma in regard to concurrent anxiety and depressive symptoms among adults with HIV/AIDS. J Health Psychol 14(3):403–413

    Article  PubMed  Google Scholar 

  • Gupta S, Aggarwal S, Kim C, Gollapudi S (1994) Human immunodeficiency virus-1 recombinant gp120 induces changes in protein kinase C isozymes: a preliminary report. Int J Immunopharmacol 16:197–204

    Article  PubMed  CAS  Google Scholar 

  • Hasler G (2010) Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry 9:155–161

    PubMed  Google Scholar 

  • Haughey NJ, Mattson MP (2002) Calcium dysregulation and neuronal apoptosis by the HIV-1 proteins Tat and gp120. JAIDS 31(Suppl 2):S55–S61

    PubMed  CAS  Google Scholar 

  • Haughey NJ, Nath A, Mattson MP, Slevin JT, Geiger JD (2001) HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. J Neurochem 78:457–467

    Article  PubMed  CAS  Google Scholar 

  • Hoyt KR, Reynolds IJ (1996) Localization of D1 dopamine receptors on live cultured striatal neurons by quantitative fluorescence microscopy. Brain Res 731:21–30

    Article  PubMed  CAS  Google Scholar 

  • Itoh K, Mehraein P, Weis S (2000) Neuronal damage of the substantia nigra in HIV-infected brains. Acta Neuropathol 99:376–384

    Article  PubMed  CAS  Google Scholar 

  • Jones G, Power C (2006) Regulation of neural cell survival by HIV-1 infection. Neurobiol Dis 21:1–17

    Article  PubMed  CAS  Google Scholar 

  • Kadiu I, Ricardo-Dukelow M, Ciborowski P, Gendelman HE (2007) Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells. J Immunol 178:6404–6415

    PubMed  CAS  Google Scholar 

  • Kanmogne GD, Schall K, Leibhart J, Knipe B, Gendelman HE, Persidsky Y (2007) HIV-1 gp120 compromises blood–brain barrier integrity and enhance monocyte migration across blood–brain barrier: implication for viral neuropathogenesis. J Cereb Blood Flow Metab 27(1):123–134

    Article  PubMed  CAS  Google Scholar 

  • Karn J (1999) Tackling Tat. J Mol Biol 293:235–254

    Article  PubMed  CAS  Google Scholar 

  • Kaul M (2008) HIV’s double strike at the brain: neuronal toxicity and compromised neurogenesis. Front Biosci 13:2484–2494

    Article  PubMed  CAS  Google Scholar 

  • Khairova RA, Machado-Vieira R, Du J, Manji HK (2009) A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 12(4):561–578

    Article  PubMed  CAS  Google Scholar 

  • Kim HJ, Martemyanov KA, Thayer SA (2008) Human immunodeficiency virus protein tat induces synapse loss via a reversible process that is distinct from cell death. J Neurosci 28(48):12604–12613

    Article  PubMed  CAS  Google Scholar 

  • King JE, Eugenin EA, Buckner CM, Berman JW (2006) HIV Tat and neurotoxicity. Microbes Infect 8(5):1347–1357

    Article  PubMed  CAS  Google Scholar 

  • Kinyanda E, Hoskins S, Nakku J, Nawaz S, Patel V (2011) Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda. Psychiatry 11:205

    PubMed  Google Scholar 

  • Köller H, Schaal H, Freund M, Garrido SR, von Giesen HJ, Ott M, Rosenbaum C, Arendt G (2001) HIV-1 protein Tat reduces the glutamate-induced intracellular Ca2+ increase in cultured cortical astrocytes. Eur JNeurosci 14:1793–1799, PubMed: 11860474

    Article  Google Scholar 

  • Kraft-Terry SD, Stothert AR, Buch S, Gendelman HE (2010) HIV-1 neuroimmunity in the era of antiretroviral therapy. Neurobiol Dis 37:542–548

    Article  PubMed  CAS  Google Scholar 

  • Krishnadas R, Cavanagh J (2012) Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry 83:495–502

    Article  PubMed  Google Scholar 

  • Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455(7215):894–902

    Article  PubMed  CAS  Google Scholar 

  • Kruman II, Nath A, Mattson MP (1998) HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp Neurol 154:276–288

    Article  PubMed  CAS  Google Scholar 

  • Kumar AM, Fernandez JB, Singer EJ, Commins D, Waldrop-Valverde D, Ownby RL, Kumar M (2009) Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains. Journal of NeuroVirology 15:257–274

    Article  PubMed  CAS  Google Scholar 

  • Lavi E, Strizki JM, Ulrich AM, Zhang W, Fu L, Wang Q, O’Connor M, Hoxie JA, González-Scarano F (1997) CXCR-4 (Fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons. Am J Pathol 151(4):1035–1042

    PubMed  CAS  Google Scholar 

  • Leonard BE (2010) The concept of depression as a dysfunction of the immune system. Curr Immunol Rev 6(3):205–212

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ (2000) Uptake of HIV-1 Tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med 6:1380–1387

    Article  PubMed  CAS  Google Scholar 

  • Loftis JM, Huckans M, Morasco BJ (2008) Neuroimmune mechanisms of cytokine-induced: current theories and novel treatment strategies. Nature 455(7215):894–902

    Article  Google Scholar 

  • Lohoff FW (2010) Overview of the genetics of major depressive disorder. Curr Psychiatry Rep 12(6):539–546

    Article  PubMed  Google Scholar 

  • Lynch DR, Guttmann RP (2002) Excitotoxicity: perspectives based on N-methyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther 300:717–723

    Article  PubMed  CAS  Google Scholar 

  • Maletic V, Robinson M, Oakes T, Iyengar S, Ball SG, Russel J (2007) Neurobiology of depression: an integrated view of key findings. Int J Clin Pract 61(12):2030–2040

    Article  PubMed  CAS  Google Scholar 

  • Maragos WF, Young KL, Turchan JT, Guseva M, Pauly JR, Nath A, Cass WA (2002) Human immunodeficiency virus-1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function. J Neurochem 83(4):955–963

    Article  PubMed  CAS  Google Scholar 

  • Masci AM, Galgani M, Cassano S, De Simone S, Gallo A, De Rosa V, Zappacosta S, Racioppi L (2003) HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling. J Leukoc Biol 74:1117–1124

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, Haughey NJ, Nath A (2005) Cell death in HIV dementia nature publishing group. Cell Death and Differ 12:893–904

    Article  CAS  Google Scholar 

  • Merril JE (1993) Cytokines and HIV-1 in neural-immune interactions. Adv Neuroimmunol 3:17–30

    Article  Google Scholar 

  • Miller AH, Maletic V, Raison L (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741

    Article  PubMed  CAS  Google Scholar 

  • Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202:13–23

    Article  PubMed  CAS  Google Scholar 

  • Missale C, Fiorentini C, Busi C, Collo G, Spano PF (2006) The NMDA/D1 receptor complex as a new target in drug development. Curr Top Med Chem 6:801–808

    Article  PubMed  CAS  Google Scholar 

  • Mitchell ES, Snyder-keller A (2003) Blockade of D1 dopaminergic transmission alleviates c-fos induction and cleaved caspase-3 expression in the brains of rat pups exposed to prenatal cocaine or perinatal asphyxia. Exp Neurol 182:64–74

    Article  PubMed  CAS  Google Scholar 

  • Mocchetti I, Nosheny RL, Tanda G, Ren K, Meyer EM (2007) Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1 protein gp120 neurotoxicity in the rat nigrostriatal system. Ann N Y Acad Sci 1122:144–154

    Article  PubMed  CAS  Google Scholar 

  • Nath A, Anderson C, Jones M, Maragos W, Booze R, Mactutus C, Bell J, Hauser KF, Mattson M (2000) Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia. J Psychopharmacol 14(3):222–227

    Article  PubMed  CAS  Google Scholar 

  • Neto FL, Borges G, Torres-Sanchez S, Mico JA, Berrocoso E (2011) Neurotrophins role in depression neurobiology: a review of basic and clinical evidence. Curr Neuropharmacol 9(4):530–552

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • O’Donnell LA, Agrawal A, Jordan-Sciutto KL, Dichter MA, Lynch DR, Kolson DL (2006) Human immunodeficiency virus (HIV)-induced neurotoxicity: roles for the NMDA receptor subtypes 2Aand 2B and the calcium-activated protease calpain by a CSF-derived HIV-1 strain. J Neurosci 26(3):981–990

    Article  PubMed  Google Scholar 

  • Ownby RL, Kumar AM, Fernandez JB, Moleon-Borodowsky I, Gonzalez L, Eisdorfer S, Waldrop-Valverde D, Kumar M (2009) Tumor necrosis factor-alpha levels in HIV-1 seropositive injecting drug users. J Neuroimmune Pharmacol 4:350–358

    Article  PubMed  Google Scholar 

  • Pace TWW, Hu F, Miller AH (2007) Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 21(1):9–19

    Article  PubMed  CAS  Google Scholar 

  • Pei L, Lee FJ, Moszynska A, Vukusic B, Liu F (2004) Regulation of dopamine D1 receptor function by physical interaction with the NMDA receptors. J Neurosci 24:1149–1158

    Article  PubMed  CAS  Google Scholar 

  • Pérez-De la Cruz V, Carillo-Mora P, Santamaría A (2012) Quinolinic acid, an endogenous molecule combining excitotoxicity, oxidative stress and other toxic mechanisms. Int J Tryptophan Res 5:1–8

    PubMed  Google Scholar 

  • Phillips K (2004) Depression in HIV-infected patients: allopathic, complementary, and alternative treatments. J Psychosom Res 57:339–351

    PubMed  Google Scholar 

  • Pieper AA, Treisman G (2005) Drug treatment of depression in HIV-positive patients: safety considerations. Drug Saf 28(9):753–762

    Article  PubMed  CAS  Google Scholar 

  • Pulliam L, Clarke JA, McGuire D, McGrath MS (1994) Investigation of HIV-infected macrophage neurotoxin production from patients with AIDS dementia. Adv Neuroimmunol 4:195–198

    Article  PubMed  CAS  Google Scholar 

  • Purohit V, Rapaka R, Shurtleff D (2011) Drugs of abuse, dopamine, and HIV-associated neurocognitive disorders/HIV-associated dementia. Mol Neurobiology 44(1):102–110

    Article  CAS  Google Scholar 

  • Readler TJ (2011) Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatr 24:519–525

    Google Scholar 

  • Sa MJ, Madeira MD, Ruela C, Volk B, Mota-Miranda A, Paula-Barbosa MM (2004) Dendritic changes in the hippocampal formation of AIDS patients: a quantitative Golgi study. Acta Neuropathol (Berl) 107:97–110

    Article  CAS  Google Scholar 

  • Samikkannu T, Saiyed ZM, Rao KVK, Babu DK, Rodriguez JW, Papuashvili MN, Nair MPN (2009) Differential regulation of indoleamine-2,3-dioxygenase (IDO) by HIV type 1 clade B and C Tat protein. AIDS Res Human Retrovirouses 25:3

    Google Scholar 

  • Saxena SK, Tiwari S, Nair MPN (2012) A global perspective on HIV/AIDS. Science 337:798

    Article  PubMed  CAS  Google Scholar 

  • Schuster R, Bornovalova M, Hunt E (2012) The influence of depression on the progression of HIV: direct and indirect effects. Behav Modif 36:123–145

    Article  PubMed  Google Scholar 

  • Shimizu SM, Chow DC, Valcour V, Masaki K, Nakamoto B, Kallianpur KJ, Shikuma C (2011) The impact of depressive symptoms on neuropsychological performance tests in HIV-infected individuals: a study of the Hawaii aging with HIV cohort. World J AIDS 1(4):139–145

    Article  PubMed  Google Scholar 

  • Stellwagen D, Beattie EC, Seo JY, Malenka RC (2005) Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 25(12):3219–3228

    Article  PubMed  CAS  Google Scholar 

  • Strazza M, Pirrone V, Wigdahl B, Nonnemacher MR (2011) Breaking down the barrier: the effects of HIV-1 on the blood-brain barrier. Brain Res 1399:96–115

    Article  PubMed  CAS  Google Scholar 

  • Takahashi H, Kato M, Takano H, Arakawa R, Okumura M, Otsuka T, Kodaka F, Hayashi M, Okubo Y, Ito H, Suhara T (2008) Differential contributions of prefrontal and hippocampal dopamine D(1) and D(2) receptors in human cognitive functions. J Neurosci 28(46):12032–12038

    Article  PubMed  CAS  Google Scholar 

  • Thornton P, Pinteaux E, Gibson RM, Allan SM, Rothwell NJ (2006) Interleukin-1-induced neurotoxicity is mediated by glia and requires caspase activation and free radical release. J Neurochem 98(1):258–266

    Google Scholar 

  • UNAIDS/WHO (2009) AIDS epidemic update. WHO Library Cataloguing-in-Publication. http://data.unaids.org/pub/report/2009/jc1700_epi_update_2009_en.pdf. Accessed 9 Jun 2012

  • UNAIDS/WHO (2012) Global report—UNAIDS report on the global AIDS epidemic/2012. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_UNAIDS_Global_Report_2012_en.pdf. Accessed in 24 Apr 2013

  • Waxman EA, Lynch DR (2005) N-Methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease. Neuroscientist 11:37–49

    Article  PubMed  CAS  Google Scholar 

  • Wolff LC, Alvarado MR, Wolff RM (2010) Prevalencia, factores de riesgo y manejo de la depresión en pacientes con infección por VIH: revisión de la literatura. Rev Chi Infectol 27(n1):65–74

    Google Scholar 

  • Xu H, Bae M, Tovar-y-Romo LB, Patel N, Bandaru VVR, Pomerantz D, Steiner JP, Haughey NJ (2011) The human immunodeficiency virus coat protein gp120 promotes forward trafficking and surface clustering of NMDA receptors in membrane microdomains. J Neurosci 31(47):17074–17090

    Article  PubMed  CAS  Google Scholar 

  • Yao H, Bethel-Brown C, Li CZ, Buch SJ (2010) HIV neuropathogenesis: a tight rope walk of innate immunity. J Neuroimmune Pharmacol 5:489–495

    Article  PubMed  Google Scholar 

  • Zheng J, Thylin MR, Ghorpade A, Xiong H, Persidsky Y, Cotter R, Niemann D, Che M, Zeng YC, Gelbard HA, Shepard RB, Swartz JM, Gendelman HE (1999) Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia. J Neuroimmunol 98:185–200

    Article  PubMed  CAS  Google Scholar 

  • Zheng L, Yang Y, Guocai L, Pauza CD, Salvato MS (2007) HIV tat protein increases bcl-2 expression in monocytes which inhibits monocyte apoptosis induced by tumor necrosis factor-alpha-related apoptosis-induced ligand. Intervirology 50(3):224–228

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Maria Isabel Soares Feitosa and Junio Pereira Pardins for their support during the preparation of this article.

Conflict of interest

We declare that we do not have conflicts of interest.

Author information

Authors and Affiliations

  1. Faculdade de Ciências da Saude, Universidade Federal da Grande Dourados Unidade II, Rodovia MS 162 (Dourados - Itaum), Km 12, Dourados, Mato Grosso do Sul, Brazil

    F. B. Del Guerra, J. L. I. Fonseca, V. M. Figueiredo & E. Castelon Konkiewitz

  2. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA

    E. B. Ziff

Authors
  1. F. B. Del Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. L. I. Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. M. Figueiredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. B. Ziff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Castelon Konkiewitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Castelon Konkiewitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Del Guerra, F.B., Fonseca, J.L.I., Figueiredo, V.M. et al. Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways. J. Neurovirol. 19, 314–327 (2013). https://doi.org/10.1007/s13365-013-0177-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-013-0177-7

Keywords

Search

Navigation