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Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV

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Abstract

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women’s Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p < 0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p < 0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p = 0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.

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References

  • Bacon MC, von Wyl V, Alden C, Sharp G, Robison E, Hessol N, Gange S, Barranday Y, Holman S, Weber K, Young MA (2005) The women’s interagency HIV study: an observational cohort brings clinical sciences to the bench. Clin Diagn Lab Immunol 12:1013–1019

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barkan SE, Melnick SL, Preston-Martin S, Weber K, Kalish LA, Miotti P, Young M, Greenblatt R, Sacks H, Feldman J (1998) The women’s interagency HIV study. WIHS Collaborative Study Group. Epidemiology 9:117–125

    Article  CAS  PubMed  Google Scholar 

  • Benedict RHB, Schretlen D, Groninger L, Brandt J (1998). Hopkins verbal learning test-revised: normative data and analysis of inter-form and test-retest relability. Clin Neuropsychol 12

  • Bluhm RL, Williamson PC, Osuch EA, Frewen PA, Stevens TK, Boksman K, Neufeld RW, Theberge J, Lanius RA (2009) Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. J Psychiatry Neurosci 34:187–194

    PubMed  PubMed Central  Google Scholar 

  • Bremner JD (2007) Neuroimaging in posttraumatic stress disorder and other stress-related disorders. Neuroimaging Clin N Am 17:523–38, ix

    Article  PubMed  PubMed Central  Google Scholar 

  • Bremner JD, Narayan M, Staib LH, Southwick SM, McGlashan T, Charney DS (1999) Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry 156:1787–1795

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bremner JD, Vythilingam M, Vermetten E, Southwick SM, McGlashan T, Nazeer A, Khan S, Vaccarino LV, Soufer R, Garg PK, Ng CK, Staib LH, Duncan JS, Charney DS (2003) MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am J Psychiatry 160:924–932

    Article  PubMed  Google Scholar 

  • Brief DJ, Bollinger AR, Vielhauer MJ, Berger-Greenstein JA, Morgan EE, Brady SM, Buondonno LM, Keane TM (2004) Understanding the interface of HIV, trauma, post-traumatic stress disorder, and substance use and its implications for health outcomes. AIDS Care 16(Suppl 1):S97–S120

    Article  PubMed  Google Scholar 

  • Buckner RL, Logan J, Donaldson DI, Wheeler ME (2000) Cognitive neuroscience of episodic memory encoding. Acta Psychol (Amst) 105:127–139

    Article  CAS  Google Scholar 

  • Cabeza R (2002) Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging 17:85–100

    Article  PubMed  Google Scholar 

  • Castelo JM, Sherman SJ, Courtney MG, Melrose RJ, Stern CE (2006) Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology 66:1688–1695

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Li L, Xu B, Liu J (2009) Insular cortex involvement in declarative memory deficits in patients with post-traumatic stress disorder. BMC Psychiatry 9:39

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohen J (1992) A power primer. Psychol Bull 112:155–159

    Article  CAS  PubMed  Google Scholar 

  • Cohen S, Williamson G (1988) Perceived stress in a probability sample of the United States. In: Spacapan S, Oskamp S (eds) The social psychology of health: claremont symposium on applied social psychology. Sage, Newbury Park

    Google Scholar 

  • Cohen S, Kamarck T, Mermelstein R (1983) A global measure of perceived stress. J Health Soc Behav 24:385–396

    Article  CAS  PubMed  Google Scholar 

  • Cook JA, Cohen MH, Burke J, Grey D, Anastos K, Kirstein L, Palacio H, Richardson J, Wilson T, Young M (2002) Effects of depressive symptoms and mental health quality of life on use of highly active antiretroviral therapy among HIV-seropositive women. J Acquir Immune Defic Syndr 30:401–409

    Article  PubMed  Google Scholar 

  • Delis DC, Freeland J, Kramer JH, Kaplan E (1988) Integrating clinical assessment with cognitive neuroscience: construct validation of the California Verbal Learning Test. J Consult Clin Psychol 56:123–130

    Article  CAS  PubMed  Google Scholar 

  • Dickerson BC, Eichenbaum H (2010) The episodic memory system: neurocircuitry and disorders. Neuropsychopharmacology 35:86–104

    Article  PubMed  Google Scholar 

  • Euston DR, Gruber AJ, McNaughton BL (2012) The role of medial prefrontal cortex in memory and decision making. Neuron 76:1057–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geuze E, Vermetten E, Ruf M, de Kloet CS, Westenberg HG (2008) Neural correlates of associative learning and memory in veterans with posttraumatic stress disorder. J Psychiatr Res 42:659–669

    Article  PubMed  Google Scholar 

  • Graham AM, Pfeifer JH, Fisher PA, Carpenter S, Fair DA (2015) Early life stress is associated with default system integrity and emotionality during infancy. J Child Psychol Psychiatry 56:1212–1222

    Article  PubMed  PubMed Central  Google Scholar 

  • Hayes JP, Hayes SM, Mikedis AM (2012) Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol Mood Anxiety Disord 2:9

    Article  PubMed  PubMed Central  Google Scholar 

  • Jenkins MA, Langlais PJ, Delis D, Cohen R (1998) Learning and memory in rape victims with posttraumatic stress disorder. Am J Psychiatry 155:278–279

    CAS  PubMed  Google Scholar 

  • Lanius RA, Williamson PC, Densmore M, Boksman K, Gupta MA, Neufeld RW, Gati JS, Menon RS (2001) Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. Am J Psychiatry 158:1920–1922

    Article  CAS  PubMed  Google Scholar 

  • Lupien SJ, de Leon M, de Santi S, Convit A, Tarshish C, Nair NP, Thakur M, McEwen BS, Hauger RL, Meaney MJ (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1:69–73

    Article  CAS  PubMed  Google Scholar 

  • Lupien SJ, Maheu F, Tu M, Fiocco A, Schramek TE (2007) The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition. Brain Cogn 65:209–237

    Article  CAS  PubMed  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    Article  CAS  PubMed  Google Scholar 

  • Machtinger EL, Wilson TC, Haberer JE, Weiss DS (2012) Psychological trauma and PTSD in HIV-positive women: a meta-analysis. AIDS Behav 16:2091–2100

    Article  CAS  PubMed  Google Scholar 

  • Maki PM, Cohen MH, Weber K, Little DM, Fornelli D, Rubin LH, Perschler P, Gould F, Martin E (2009) Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: a preliminary study. Neurology 72:1661–1668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maki PM, Rubin LH, Cohen M, Golub ET, Greenblatt RM, Young M, Schwartz RM, Anastos K, Cook JA (2012) Depressive symptoms are increased in the early perimenopausal stage in ethnically diverse human immunodeficiency virus-infected and human immunodeficiency virus-uninfected women. Menopause 19:1215–1223

    Article  PubMed  PubMed Central  Google Scholar 

  • Maki PM, Rubin LH, Valcour V, Martin E, Crystal H, Young M, Weber KM, Manly J, Richardson J, Alden C, Anastos K (2015) Cognitive function in women with HIV: findings from the Women’s Interagency HIV Study. Neurology 84:231–240

    Article  PubMed  PubMed Central  Google Scholar 

  • Meyer VJ, Little DM, Fitzgerald DA, Sundermann EE, Rubin LH, Martin EM, Weber KM, Cohen MH, Maki PM (2014) Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection. J Neurovirol 20:352–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Doherty DC, Chitty KM, Saddiqui S, Bennett MR, Lagopoulos J (2015) A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res 232:1–33

    Article  PubMed  Google Scholar 

  • Ortega M, Brier MR, Ances BM (2015) Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity. AIDS 29:703–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel R, Spreng RN, Shin LM, Girard TA (2012) Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neurosci Biobehav Rev 36:2130–2142

    Article  PubMed  Google Scholar 

  • Pukay-Martin ND, Cristiani SA, Saveanu R, Bornstein RA (2003) The relationship between stressful life events and cognitive function in HIV-infected men. J Neuropsychiatry Clin Neurosci 15:436–441

    Article  PubMed  Google Scholar 

  • Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Article  Google Scholar 

  • Raichle ME (2015) The brain’s default mode network. Annu Rev Neurosci 38:433–447

    Article  CAS  PubMed  Google Scholar 

  • Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci U S A 98:676–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramage AE, Laird AR, Eickhoff SB, Acheson A, Peterson AL, Williamson DE, Telch MJ, Fox PT (2013) A coordinate-based meta-analytic model of trauma processing in posttraumatic stress disorder. Hum Brain Mapp 34:3392–3399

    Article  PubMed  Google Scholar 

  • Rubin LH, Cook JA, Grey DD, Weber K, Wells C, Golub ET, Wright RL, Schwartz RM, Goparaju L, Cohan D, Wilson ML, Maki PM (2011) Perinatal depressive symptoms in HIV-infected versus HIV-uninfected women: a prospective study from preconception to postpartum. J Womens Health (Larchmt) 20:1287–1295

    Article  Google Scholar 

  • Rubin LH, Cook JA, Weber KM, Cohen MH, Martin E, Valcour V, Milam J, Anastos K, Young MA, Alden C, Gustafson DR, Maki PM (2015a) The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women. J Neurovirol 21:422–432

    Article  PubMed  PubMed Central  Google Scholar 

  • Rubin LH, Meyer VM, Jamadar R, Sundermann EE, Wu M, Weber KM, Cohen MH, Little DM, Maki PM (2015b) Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women. Neurobiol Dis

  • Shin LM, Shin PS, Heckers S, Krangel TS, Macklin ML, Orr SP, Lasko N, Segal E, Makris N, Richert K, Levering J, Schacter DL, Alpert NM, Fischman AJ, Pitman RK, Rauch SL (2004) Hippocampal function in posttraumatic stress disorder. Hippocampus 14:292–300

    Article  PubMed  Google Scholar 

  • Shin LM, Rauch SL, Pitman RK (2006) Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann N Y Acad Sci 1071:67–79

    Article  PubMed  Google Scholar 

  • Soares JM, Sampaio A, Ferreira LM, Santos NC, Marques P, Marques F, Palha JA, Cerqueira JJ, Sousa N (2013) Stress impact on resting state brain networks. PLoS One 8, e66500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sperling R, Greve D, Dale A, Killiany R, Holmes J, Rosas HD, Cocchiarella A, Firth P, Rosen B, Lake S, Lange N, Routledge C, Albert M (2002) Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A 99:455–460

    Article  CAS  PubMed  Google Scholar 

  • Spies G, Afifi TO, Archibald SL, Fennema-Notestine C, Sareen J, Seedat S (2012) Mental health outcomes in HIV and childhood maltreatment: a systematic review. Syst Rev 1:30

    Article  PubMed  PubMed Central  Google Scholar 

  • Stricker JL, Brown GG, Wixted J, Baldo JV, Delis DC (2002) New semantic and serial clustering indices for the California Verbal Learning Test-Second Edition: background, rationale, and formulae. J Int Neuropsychol Soc 8:425–435

    Article  PubMed  Google Scholar 

  • Sundermann EE, Bishop JR, Rubin LH, Little DM, Meyer VJ, Martin E, Weber K, Cohen M, Maki PM (2015) Genetic predictor of working memory and prefrontal function in women with HIV. J Neurovirol 21:81–91

    Article  PubMed  Google Scholar 

  • Tulving E, Kapur S, Craik FI, Moscovitch M, Houle S (1994) Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proc Natl Acad Sci U S A 91:2016–2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valcour V, Rubin LH, Tien P, Anastos K, Young M, Mack W, Cohen M, Golub ET, Crystal H, Maki PM (2015) Human immunodeficiency virus (HIV) modulates the associations between insulin resistance and cognition in the current combination antiretroviral therapy (cART) era: a study of the Women’s Interagency HIV Study (WIHS). J Neurovirol 21:415–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weathers FW, Huska JA, Keane TM (1991) PCL-C for DSM-IV. Division NCfPBS, (ed): Boston

  • Woods SP, Scott JC, Dawson MS, Morgan EE, Carey CL, Heaton RK, Grant I, Group HIVNRC (2005) Construct validity of Hopkins Verbal Learning Test-Revised component process measures in an HIV-1 sample. Arch Clin Neuropsychol 20:1061–1071

    Article  PubMed  Google Scholar 

  • Yehuda R, Keefe RS, Harvey PD, Levengood RA, Gerber DK, Geni J, Siever LJ (1995) Learning and memory in combat veterans with posttraumatic stress disorder. Am J Psychiatry 152:137–139

    Article  CAS  PubMed  Google Scholar 

  • Zhao YJ, Du MY, Huang XQ, Lui S, Chen ZQ, Liu J, Luo Y, Wang XL, Kemp GJ, Gong QY (2014) Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis. Psychol Med 44:2927–2937

    Article  PubMed  Google Scholar 

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Acknowledgments

Data in this manuscript were collected by the Chicago site of the Women’s Interagency HIV study (WIHS) and is funded by the National Institute of Allergy and Infectious Diseases (NIAID) grant U01 A1034993 (PI: Mardge Cohen, M.D.) and co-funded by the National Cancer Institute (NCI) and National Institute of Drug Abuse (NIDA). L. Rubin’s effort was supported by grant number 1K01MH098798-01 from the National Institute of Mental Health (NIMH) and grant number K12HD055892 from the National Institute of Child Health and Human Development (NICHD), and the National Institutes of Health Office of Research on Women’s Health (ORWH). This grant was also supported by the Chicago Developmental Center for AIDS Research (D-CFAR), an NIH funded program (P30 AI 082151), which is supported by the following NIH Institutes and Centers (NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NCCAM). V. Meyer’s effort on this project was supported by the National Institute on Drug Abuse (1F31DA028573). E. Sundermann’s effort on this project was supported by the National Institute of Mental Health (1F31MH083537). This work was previously presented in part as part of an oral presentation at the 6th International Workshop on HIV and Aging on October 5 in Washington, DC and as part of a poster presentation at the 13th International Symposium on Neurovirology on June 3 in San Diego, California.

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Leah H. Rubin and Minjie Wu are equally contributing first authors

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Rubin, L.H., Wu, M., Sundermann, E.E. et al. Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV. J. Neurovirol. 22, 840–851 (2016). https://doi.org/10.1007/s13365-016-0446-3

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