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01-10-2018

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV

Authors: Roger C. McIntosh, Robert Paul, Lishomwa C. Ndhlovu, Melissa Hidalgo, Judith D. Lobo, Maegen Walker, Cecilia M. Shikuma, Kalpana J. Kallianpur

Published in: Journal of NeuroVirology | Issue 5/2018

Abstract

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.

Alexopoulos GS, Hoptman MJ, Kanellopoulos D, Murphy CF, Lim KO, Gunning FM (2012) Functional connectivity in the cognitive control network and the default mode network in late-life depression. J Affect Disord 139(1):56–65CrossRef

Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L, Mathews VP, Kalnin A, Lowe MJ (2005) Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry 57(10):1079–1088CrossRef

Ances BM, Ortega M, Vaida F, Heaps J, Paul R (2012) Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr (1999) 59(5):469–477CrossRef

Anderson AM, Croteau D, Ellis RJ, Rosario D, Potter M, Guillemin GJ, Brew BJ, Woods SP, Letendre SL (2018) HIV, prospective memory, and cerebrospinal fluid concentrations of quinolinic acid and phosphorylated tau. J Neuroimmunol 319:13–18CrossRef

Appay V, Sauce D (2008) Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol 214(2):231–241CrossRef

Barak O, Goshen I, Ben-Hur T, Weidenfeld J, Taylor AN, Yirmiya R (2002) Involvement of brain cytokines in the neurobehavioral disturbances induced by HIV-1 glycoprotein120. Brain Res 933(2):98–108CrossRef

Beck AT et al (1961) An inventory for measuring depression. Arch Gen Psychiatry 4(6):561–571CrossRef

Behrman-Lay AM, Paul RH, Heaps-Woodruff J, Baker LM, Usher C, Ances BM (2016) Human immunodeficiency virus has similar effects on brain volumetrics and cognition in males and females. J Neurovirol 22(1):93–103CrossRef

Chaganti J et al (2017) Functional connectivity in virally suppressed patients with HIV-associated neurocognitive disorder: a resting-state analysis. Am J Neuroradiol 38(8):1623–1629CrossRef

Chumbley J, Worsley K, Flandin G, Friston K (2010) Topological FDR for neuroimaging. Neuroimage 49(4):3057–3064CrossRef

Clark US, Cohen RA, Sweet LH, Gongvatana A, Devlin KN, Hana GN, Westbrook ML, Mulligan RC, Jerskey BA, White TL, Navia B, Tashima KT (2012) Effects of HIV and early life stress on amygdala morphometry and neurocognitive function. J Int Neuropsychol Soc 18(4):657–668CrossRef

Clark US, Sweet LH, Morgello S, Philip NS, Cohen RA (2017) High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults. Brain Imaging Behav 11(3):649–665CrossRef

Cole SW (2008) Psychosocial influences on HIV-1 disease progression: neural, endocrine, and virologic mechanisms. Psychosom Med 70(5):562–568CrossRef

Connolly CG, Wu J, Ho TC, Hoeft F, Wolkowitz O, Eisendrath S, Frank G, Hendren R, Max JE, Paulus MP, Tapert SF, Banerjee D, Simmons AN, Yang TT (2013) Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biol Psychiatry 74(12):898–907CrossRef

Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29(3):162–173CrossRef

Dantzer R, BLUTHÉ R, Laye S, BRET‐DIBAT JL, Parnet P, Kelley KW (1998) Cytokines and sickness behavior. Annals of the New York Academy of Sciences 840(1):586–90CrossRef

Dantzer R (2016) Role of the kynurenine metabolism pathway in inflammation-induced depression: preclinical approaches. Inflammation-Associated Depression: Evidence, Mechanisms and Implications, Springer: 117–138

Del Guerra F et al (2013) Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways. J Neurovirol 19(4):314–327CrossRef

DeWitt SJ, Bradley KA, Lin N, Yu C, Gabbay V (2018) A pilot resting-state functional connectivity study of the kynurenine pathway in adolescents with depression and healthy controls. J Affect Disord 227:752–758CrossRef

Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Front Syst Neurosci 4:19PubMedPubMedCentral

Fransson P, Marrelec G (2008) The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. Neuroimage 42(3):1178–1184CrossRef

Frodl T, Amico F (2014) Is there an association between peripheral immune markers and structural/functional neuroimaging findings? Prog Neuro-Psychopharmacol Biol Psychiatry 48:295–303CrossRef

Gostner JM et al (2015) Disturbed amino acid metabolism in HIV: association with neuropsychiatric symptoms. Front Psychiatry 6:97CrossRef

Greicius MD, Krasnow B, Reiss AL, Menon V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci 100(1):253–258CrossRef

Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF (2007) Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry 62(5):429–437CrossRef

Guha A, Wang L, Tanenbaum A, Esmaeili-Firidouni P, Wendelken LA, Busovaca E, Clifford K, Desai A, Ances BM, Valcour V (2016) Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60. J Neurovirol 22(1):80–87CrossRef

Guo W-B, Liu F, Xue ZM, Xu XJ, Wu RR, Ma CQ, Wooderson SC, Tan CL, Sun XL, Chen JD, Liu ZN, Xiao CQ, Chen HF, Zhao JP (2012) Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: a resting-state fMRI study. Prog Neuro-Psychopharmacol Biol Psychiatry 37(1):153–160CrossRef

Gupta R, Dandu M, Packel L, Rutherford G, Leiter K, Phaladze N, Korte FPD, Iacopino V, Weiser SD (2010) Depression and HIV in Botswana: a population-based study on gender-specific socioeconomic and behavioral correlates. PLoS One 5(12):e14252CrossRef

Gusnard DA, Raichle ME (2001) Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci 2(10):685–694CrossRef

Hannestad J, Subramanyam K, DellaGioia N, Planeta-Wilson B, Weinzimmer D, Pittman B, Carson RE (2012) Glucose metabolism in the insula and cingulate is affected by systemic inflammation in humans. Journal of nuclear medicine: official publication. Society of Nuclear Medicine 53(4):601CrossRef

Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66(5):407–414CrossRef

Haroon E, Woolwine BJ, Chen X, Pace TW, Parekh S, Spivey JR, Hu XP, Miller AH (2014) IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy. Neuropsychopharmacology 39(7):1777CrossRef

Heyes M et al (1992) Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 115(5):1249–1273CrossRef

Janssen MA et al (2015) Cognitive functioning, wellbeing and brain correlates in HIV-1 infected patients on long-term combination antiretroviral therapy. AIDS 29(16):2139–2148CrossRef

Jones SP, Franco NF, Varney B, Sundaram G, Brown DA, de Bie J, Lim CK, Guillemin GJ, Brew BJ (2015) Expression of the kynurenine pathway in human peripheral blood mononuclear cells: implications for inflammatory and neurodegenerative disease. PLoS One 10(6):e0131389CrossRef

Kremer H, Lutz FPC, McIntosh RC, Dévieux JG, Ironson G (2016) Interhemispheric asymmetries and theta activity in the rostral anterior cingulate cortex as EEG signature of HIV-related depression gender matters. Clin EEG Neurosci 47(2):96–104CrossRef

Kuller LH, Tracy R, Belloso W, Wit SD, Drummond F, Lane HC, Ledergerber B, Lundgren J, Neuhaus J, Nixon D, Paton NI, Neaton JD, for the INSIGHT SMART Study Group (2008) Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 5(10):e203CrossRef

Kullmann JS, Grigoleit JS, Lichte P, Kobbe P, Rosenberger C, Banner C, Wolf OT, Engler H, Oberbeck R, Elsenbruch S, Bingel U, Forsting M, Gizewski ER, Schedlowski M (2013) Neural response to emotional stimuli during experimental human endotoxemia. Hum Brain Mapp 34(9):2217–2227CrossRef

Lawson MA, Kelley KW, Dantzer R (2011) Intracerebroventricular administration of HIV-1 tat induces brain cytokine and indoleamine 2, 3-dioxygenase expression: a possible mechanism for AIDS comorbid depression. Brain Behav Immun 25(8):1569–1575CrossRef

Leserman J (2003) HIV disease progression: depression, stress, and possible mechanisms. Biol Psychiatry 54(3):295–306CrossRef

Lewis CM, Baldassarre A, Committeri G, Romani GL, Corbetta M (2009) Learning sculpts the spontaneous activity of the resting human brain. Proc Natl Acad Sci 106(41):17558–17563CrossRef

Lieberman MD, Cunningham WA (2009) Type I and type II error concerns in fMRI research: re-balancing the scale. Social cognitive and affective neuroscience: nsp052

Liu C-H, Ma X, Wu X, Fan TT, Zhang Y, Zhou FC, Li LJ, Li F, Tie CL, Li SF, Zhang D, Zhou Z, Dong J, Wang YJ, Yao L, Wang CY (2013a) Resting-state brain activity in major depressive disorder patients and their siblings. J Affect Disord 149(1):299–306CrossRef

Liu F, Guo W, Liu L, Long Z, Ma C, Xue Z, Wang Y, Li J, Hu M, Zhang J, du H, Zeng L, Liu Z, Wooderson SC, Tan C, Zhao J, Chen H (2013b) Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: a resting-state fMRI study. J Affect Disord 146(3):401–406CrossRef

Marchetti I, Koster EHW, Sonuga-Barke EJ, de Raedt R (2012) The default mode network and recurrent depression: a neurobiological model of cognitive risk factors. Neuropsychol Rev 22(3):229–251CrossRef

Musgrove DR, Eberly LE, Klimes-Dougan B, Basgoze Z, Thomas KM, Mueller BA, Houri A, Lim KO, Cullen KR (2015) Impaired bottom-up effective connectivity between amygdala and subgenual anterior cingulate cortex in unmedicated adolescents with major depression: results from a dynamic causal modeling analysis. Brain Connect 5(10):608–619CrossRef

Ochsner KN, Ray RD, Cooper JC, Robertson ER, Chopra S, Gabrieli JDE, Gross JJ (2004) For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. Neuroimage 23(2):483–499CrossRef

O'Connor M-F, Irwin MR, Wellisch DK (2009) When grief heats up: pro-inflammatory cytokines predict regional brain activation. Neuroimage 47(3):891–896CrossRef

Olley BO, Gxamza F, Seedat S, Theron H, Taljaard J, Reid E, Reuter H, Stein DJ (2003) Psychopathology and coping in recently diagnosed HIV/AIDS patients-the role of gender. S Afr Med J 93(12):928–931PubMed

Pala AN, Steca P, Bagrodia R, Helpman L, Colangeli V, Viale P, Wainberg ML (2016) Subtypes of depressive symptoms and inflammatory biomarkers: an exploratory study on a sample of HIV-positive patients. Brain Behav Immun 56:105–13

Power JD, Mitra A, Laumann TO, Snyder AZ, Schlaggar BL, Petersen SE (2014) Methods to detect, characterize, and remove motion artifact in resting state fMRI. Neuroimage 84:320–341CrossRef

Prossin AR, Koch AE, Campbell PL, McInnis MG, Zalcman SS, Zubieta JK (2011) Association of plasma interleukin-18 levels with emotion regulation and μ-opioid neurotransmitter function in major depression and healthy volunteers. Biological Psychiatry 69(8):808–12CrossRef

Rabkin JG (2008) HIV and depression: 2008 review and update. Curr HIV/AIDS Rep 5(4):163–171CrossRef

Rabkin JG, Ferrando SJ, van Gorp W, Rieppi R, McElhiney M, Sewell M (2000) Relationships among apathy, depression, and cognitive impairment in HIV/AIDS. J Neuropsychiatry Clin Neurosci 12(4):451–457CrossRef

Rosenkranz MA, Busse WW, Johnstone T, Swenson CA, Crisafi GM, Jackson MM, Davidson RJ (2005) Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation. Proceedings of the National Academy of Sciences of the United States of America 102(37):13319–13324CrossRef

Roy AK, Shehzad Z, Margulies DS, Kelly AMC, Uddin LQ, Gotimer K, Biswal BB, Castellanos FX, Milham MP (2009) Functional connectivity of the human amygdala using resting state fMRI. Neuroimage 45(2):614–626CrossRef

Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, Neaton JD, Brenchley JM, Deeks SG, Sereti I, Douek DC, INSIGHT SMART Study Group (2011) Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 203(6):780–790CrossRef

Scarinci IC, Beech BM, Naumann W, Kovach KW, Pugh L, Fapohunda B (2002) Depression, socioeconomic status, age, and marital status in black women: a national study. Ethn Dis 12(3):421–428PubMed

Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, Suridjan I, Kennedy JL, Rekkas PV, Houle S, Meyer JH (2015) Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA psychiatry 72(3):268–75CrossRef

Sheline YI, Price JL, Yan Z, Mintun MA (2010) Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci 107(24):11020–11025CrossRef

Spies G, Ahmed-Leitao F, Fennema-Notestine C, Cherner M, Seedat S (2016) Effects of HIV and childhood trauma on brain morphometry and neurocognitive function. J Neurovirol 22(2):149–158CrossRef

Tadayonnejad R, Yang S, Kumar A, Ajilore O (2015) Clinical, cognitive, and functional connectivity correlations of resting-state intrinsic brain activity alterations in unmedicated depression. J Affect Disord 172:241–250CrossRef

Tahmasian M et al (2013) Aberrant intrinsic connectivity of hippocampus and amygdala overlap in the fronto-insular and dorsomedial-prefrontal cortex in major depressive disorder. Front Hum Neurosci 7:639CrossRef

Thames AD, Kuhn TP, Mahmood Z, Bilder RM, Williamson TJ, Singer EJ, Arentoft A (2018) Effects of social adversity and HIV on subcortical shape and neurocognitive function. Brain Imaging Behav 12(1):96–108CrossRef

Thomas JB, Brier MR, Snyder AZ, Vaida FF, Ances BM (2013) Pathways to neurodegeneration effects of HIV and aging on resting-state functional connectivity. Neurology 80(13):1186–1193CrossRef

Towgood KJ, Pitkanen M, Kulasegaram R, Fradera A, Soni S, Sibtain N, Reed LJ, Bradbeer C, Barker GJ, Dunn JT, Zelaya F, Kopelman MD (2013) Regional cerebral blood flow and FDG uptake in asymptomatic HIV-1 men. Hum Brain Mapp 34(10):2484–2493CrossRef

Vitkovic L, Konsman JP, Bockaert J, Dantzer R, Homburger V, Jacque C (2000) Cytokine signals propagate through the brain. Molecular psychiatry 5(6):604CrossRef

Wade BS et al (2015) Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort. NeuroImage Clin 9:564–573CrossRef

Yang H, Long XY, Yang Y, Yan H, Zhu CZ, Zhou XP, Zang YF, Gong QY (2007) Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI. Neuroimage 36(1):144–152CrossRef

Zhu X, Wang X, Xiao J, Liao J, Zhong M, Wang W, Yao S (2012) Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients. Biol Psychiatry 71(7):611–617CrossRef

Zou Q-H, Zhu CZ, Yang Y, Zuo XN, Long XY, Cao QJ, Wang YF, Zang YF (2008) An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods 172(1):137–141CrossRef

Title: Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV
Authors: Roger C. McIntosh
Robert Paul
Lishomwa C. Ndhlovu
Melissa Hidalgo
Judith D. Lobo
Maegen Walker
Cecilia M. Shikuma
Kalpana J. Kallianpur
Publication date: 01-10-2018
Publisher: Springer International Publishing
Published in: Journal of NeuroVirology / Issue 5/2018
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-018-0658-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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