Top

Published in:

01-02-2021 | Affective Disorder | Short Communication

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

Authors: Rowan Saloner, Emily W. Paolillo, Robert K. Heaton, David J. Grelotti, Murray B. Stein, Andrew H. Miller, J. Hampton Atkinson, Scott L. Letendre, Ronald J. Ellis, Igor Grant, Jennifer E. Iudicello, David J. Moore

Published in: Journal of NeuroVirology | Issue 1/2021

Abstract

We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal profiles of neurocognition in a cohort of 143 people with HIV (PWH) on antiretroviral therapy. Global neurocognition, processing speed, motor skills, and attention/working memory all worsened as CRP increased but only among PWH who, on average, exhibited moderate to severe depressive symptoms (BDI-II > 22). Findings suggest that some PWH with chronically elevated depressive symptoms may have an inflammatory subtype of depression and a particular vulnerability to neurocognitive changes that may respond to drugs targeting inflammation or its neural sequelae.

American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedPubMedCentralCrossRef

Bandera A, Taramasso L, Bozzi G, Muscatello A, Robinson JA, Burdo TH, Gori A (2019) HIV-associated neurocognitive impairment in the modern ART era: are we close to discovering reliable biomarkers in the setting of virological suppression? Frontiers in Aging Neuroscience 11:187PubMedPubMedCentralCrossRef

Bates D, Mächler M, Bolker B, Walker S (2015) Fitting linear mixed-effects models using lme4. J Stat Softw 1(1):2015

Beck A, Steer R, Brown G (1996) Manual for Beck Depression Inventory II (BDI-II). TX, Psychology Corporation, San Antonio

Bettcher BM, Kramer JH (2014) Longitudinal inflammation, cognitive decline, and Alzheimer’s disease: a mini-review. Clin Pharmacol Ther 96:464–469PubMedPubMedCentralCrossRef

Beurel E, Toups M, Nemeroff CB (2020) The bidirectional relationship of depression and inflammation: double trouble. Neuron.

Bing EG, Burnam MA, Longshore D, Fleishman JA, Sherbourne CD, London AS, Turner BJ, Eggan F, Beckman R, Vitiello B, Morton SC, Orlando M, Bozzette SA, Ortiz-Barron L, Shapiro M (2001) Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Arch Gen Psychiatry 58:721–728PubMedCrossRef

Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I, Heaton RK (2004) Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol 26:307–319PubMedCrossRef

Cysique LA, Franklin D Jr, Abramson I, Ellis RJ, Letendre S, Collier A, Clifford D, Gelman B, McArthur J, Morgello S, Simpson D, McCutchan JA, Grant I, Heaton RK, Group C, Group H (2011) Normative data and validation of a regression based summary score for assessing meaningful neuropsychological change. J Clin Exp Neuropsychol 33:505–522PubMedPubMedCentralCrossRef

Deeks SG, Tracy R, Douek DC (2013) Systemic effects of inflammation on health during chronic HIV infection. Immunity 39:633–645PubMedPubMedCentralCrossRef

Ellis RJ, Letendre SL, Atkinson JH, Clifford D, Collier AC, Gelman BB, Marra C, McCutchan JA, Morgello S, Sacktor N, Tang B, Heaton RK (2020) Higher levels of plasma inflammation biomarkers are associated with depressed mood and quality of life in aging, virally suppressed men, but not women, with HIV. Brain, Behavior, & Immunity - Health: 100121.

Felger JC (2017) The role of dopamine in inflammation-associated depression: mechanisms and therapeutic implications. Curr Top Behav Neurosci 31:199–219PubMedCrossRef

Felger JC, Haroon E, Patel TA, Goldsmith DR, Wommack EC, Woolwine BJ, Le N-A, Feinberg R, Tansey MG, Miller AH (2020) What does plasma CRP tell us about peripheral and central inflammation in depression? Molecular psychiatry 25:1301–1311PubMedCrossRef

Felger JC, Li Z, Haroon E, Woolwine BJ, Jung MY, Hu X, Miller AH (2016) Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Molecular Psychiatry 21:1358–1365PubMedCrossRef

Felger JC, Treadway MT (2017) Inflammation effects on motivation and motor activity: role of dopamine. Neuropsychopharmacology 42:216–241PubMedCrossRef

Gaynes BN, Pence BW, Eron JJ Jr, Miller WC (2008) Prevalence and comorbidity of psychiatric diagnoses based on reference standard in an HIV+ patient population. Psychosom Med 70:505–511PubMedPubMedCentralCrossRef

Guaraldi G, Brothers TD, Zona S, Stentarelli C, Carli F, Malagoli A, Santoro A, Menozzi M, Mussi C, Mussini C, Kirkland S, Falutz J, Rockwood K (2015) A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity. Aids 29:1633–1641PubMedCrossRef

Haroon E, Daguanno AW, Woolwine BJ, Goldsmith DR, Baer WM, Wommack EC, Felger JC, Miller AH (2018) Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder. Psychoneuroendocrinology 95:43–49PubMedPubMedCentralCrossRef

Haroon E, Fleischer CC, Felger JC, Chen X, Woolwine BJ, Patel T, Hu XP, Miller AH (2016) Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Mol Psychiatry 21:1351–1357PubMedPubMedCentralCrossRef

Ipser JC, Brown GG, Bischoff-Grethe A, Connolly CG, Ellis RJ, Heaton RK, Grant I, Translational Methamphetamine ARCG (2015) HIV infection is associated with attenuated frontostriatal intrinsic connectivity: a preliminary study. Journal of the International Neuropsychological Society : JINS 21:203–213PubMedCrossRef

Johnson PO, Neyman J (1936) Tests of certain linear hypotheses and their application to some educational problems. Statistical Research Memoirs 1:57–93

Koyama A, O’Brien J, Weuve J, Blacker D, Metti AL, Yaffe K (2013) The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. The journals of gerontology Series A, Biological sciences and medical sciences 68:433–440PubMedCrossRef

Lee Y, Subramaniapillai M, Brietzke E, Mansur RB, Ho RC, Yim SJ, McIntyre RS (2018) Anti-cytokine agents for anhedonia: targeting inflammation and the immune system to treat dimensional disturbances in depression. Therapeutic advances in psychopharmacology 8:337–348PubMedPubMedCentralCrossRef

Leserman J (2008) Role of depression, stress, and trauma in HIV disease progression. Psychosom Med 70:539–545PubMedCrossRef

Metti AL, Yaffe K, Boudreau RM, Simonsick EM, Carnahan RM, Satterfield S, Harris TB, Ayonayon HN, Rosano C, Cauley JA, Health ABCS (2014) Trajectories of inflammatory markers and cognitive decline over 10 years. Neurobiol Aging 35:2785–2790PubMedPubMedCentralCrossRef

Miller AH, Raison CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 16:22–34PubMedPubMedCentralCrossRef

Miller AH, Trivedi MH, Jha MK (2017) Is C-reactive protein ready for prime time in the selection of antidepressant medications? Psychoneuroendocrinology 84:206PubMedCrossRef

Montoya JL, Campbell LM, Paolillo EW, Ellis RJ, Letendre SL, Jeste DV, Moore DJ (2019) Inflammation relates to poorer complex motor performance among adults living with HIV on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr 1999(80):15–23CrossRef

Nakonezny PA, Carmody TJ, Morris DW, Kurian BT, Trivedi MH (2010) Psychometric evaluation of the Snaith-Hamilton pleasure scale in adult outpatients with major depressive disorder. Int Clin Psychopharmacol 25:328–333PubMedPubMedCentralCrossRef

Oppenheim H, Paolillo EW, Moore RC, Ellis RJ, Letendre SL, Jeste DV, Grant I, Moore DJ (2018) Neurocognitive functioning predicts frailty index in HIV. Neurology 91:e162–e170PubMedPubMedCentralCrossRef

Paolillo EW, Pasipanodya EC, Moore RC, Pence BW, Atkinson JH, Grelotti DJ, Grant I, Heaton RK, Moore DJ (2020a) Cumulative burden of depression and neurocognitive decline among persons with HIV: a longitudinal study. JAIDS Journal of Acquired Immune Deficiency Syndromes 84

Paolillo EW, Sun-Suslow N, Pasipanodya EC, Morgan EE, Ellis RJ, Jeste DV, Moore DJ (2020) Pre-frailty predicts cognitive decline at 2-year follow-up in persons living with HIV. Journal of NeuroVirology 26:168–180PubMedCrossRef

Pence BW, Mills JC, Bengtson AM, Gaynes BN, Breger TL, Cook RL, Moore RD, Grelotti DJ, O’Cleirigh C, Mugavero MJ (2018) Association of increased chronicity of depression with HIV appointment attendance, treatment failure, and mortality among HIV-infected adults in the United States. JAMA psychiatry 75:379–385PubMedPubMedCentralCrossRef

Perini G, Cotta Ramusino M, Sinforiani E, Bernini S, Petrachi R, Costa A (2019) Cognitive impairment in depression: recent advances and novel treatments. Neuropsychiatric disease and treatment 15:1249–1258PubMedPubMedCentralCrossRef

Preacher KJ, Curran PJ, Bauer DJ (2006) Computational tools for probing interactions in multiple linear regression, multilevel modeling, and latent curve analysis. Journal of educational and behavioral statistics 31:437–448CrossRef

Rabkin JG (2008) HIV and depression: 2008 review and update. Current HIV/AIDS Reports 5:163–171PubMedCrossRef

Rooney AS, Moore RC, Paolillo EW, Gouaux B, Umlauf A, Letendre SL, Jeste DV, Moore DJ (2019) Depression and aging with HIV: associations with health-related quality of life and positive psychological factors. J Affect Disord 251:1–7PubMedPubMedCentralCrossRef

Rubin LH, Benning L, Keating SM, Norris PJ, Burke-Miller J, Savarese A, Kumanan KN, Awadalla S, Springer G, Anastos K, Young M, Milam J, Valcour VG, Weber KM, Maki PM (2018) Variability in C-reactive protein is associated with cognitive impairment in women living with and without HIV: a longitudinal study. Journal of neurovirology 24:41–51PubMedCrossRef

Rubin LH, Maki PM (2019) HIV, depression, and cognitive impairment in the era of effective antiretroviral therapy. Current HIV/AIDS Reports 16:82–95PubMedPubMedCentralCrossRef

Saloner R, Cherner M, Grelotti DJ, Paolillo EW, Moore DJ, Heaton RK, Letendre SL, Kumar A, Grant I, Ellis RJ (2020) Lower CSF homovanillic acid relates to higher burden of neuroinflammation and depression in people with HIV disease. Brain Behav Immun 90:353–363PubMedCrossRef

Walker KA, Gottesman RF, Wu A, Knopman DS, Gross AL, Mosley TH Jr, Selvin E, Windham BG (2019) Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study. Neurology 92:e1256–e1267PubMedPubMedCentral

Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168PubMedPubMedCentralCrossRef

World Health Organization (1998) Composite Diagnositic International Interview (CIDI, version 2.1). World Health Organization: Geneva, Switzerland

Yao H, Mizoguchi Y, Monji A, Yakushiji Y, Takashima Y, Uchino A, Yuzuriha T, Hashimoto M (2019) Low-grade inflammation is associated with apathy indirectly via deep white matter lesions in community-dwelling older adults: the sefuri study. Int J Mol Sci 20:1905PubMedCentralCrossRef

Zheng F, Xie W (2018) High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing. Psychol Med 48:1381–1389PubMedCrossRef

Title: Chronically elevated depressive symptoms interact with acute increases in inflammation to predict worse neurocognition among people with HIV
Authors: Rowan Saloner
Emily W. Paolillo
Robert K. Heaton
David J. Grelotti
Murray B. Stein
Andrew H. Miller
J. Hampton Atkinson
Scott L. Letendre
Ronald J. Ellis
Igor Grant
Jennifer E. Iudicello
David J. Moore
Publication date: 01-02-2021
Publisher: Springer International Publishing
Keywords: Affective Disorder
Human Immunodeficiency Virus
Affective Disorder
Published in: Journal of NeuroVirology / Issue 1/2021
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-020-00925-1

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2021

Pre-clinical atherosclerosis is found at post-mortem, in the brains of men with HIV

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania

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

Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: case series and review of literature

Transcriptional signatures of Zika virus infection in astrocytes

How microcompetition with latent viruses can cause α synuclein aggregation, mitochondrial dysfunction, and eventually Parkinson’s disease