Hostname: page-component-7b9c58cd5d-v2ckm Total loading time: 0 Render date: 2025-03-15T02:58:18.855Z Has data issue: false hasContentIssue false
  • English
  • Français

Executive dysfunction in depression in adolescence: the role of inflammation and higher body mass

Published online by Cambridge University Press:  28 March 2019

Naoise Mac Giollabhui Open the ORCID record for Naoise Mac Giollabhui [Opens in a new window] ,
Dominika Swistun ,
Susan Murray ,
Daniel P. Moriarity ,
Marin M. Kautz ,
Lauren M. Ellman ,
Thomas M. Olino ,
Christopher L. Coe ,
Lyn Y. Abramson  and
Lauren B. Alloy
Naoise Mac Giollabhui
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
Dominika Swistun
Affiliation:
Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
Susan Murray
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
Daniel P. Moriarity
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
Marin M. Kautz
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
Lauren M. Ellman
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
Thomas M. Olino
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
Christopher L. Coe
Affiliation:
Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
Lyn Y. Abramson
Affiliation:
Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
Lauren B. Alloy*
Affiliation:
Department of Psychology, Temple University, Philadelphia, PA, USA
*
Author for correspondence: Lauren B. Alloy, E-mail: lalloy@temple.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

There is substantial evidence that many depressed individuals experience impaired executive functioning. Understanding the causes of executive dysfunction in depression is clinically important because cognitive impairment is a substantial contributor to functional impairment. This study investigated whether elevated levels of an inflammatory cytokine [interleukin-6 (IL-6)] and/or higher body mass index (BMI) concurrently and/or prospectively accounted for the relationship between depressive symptoms and impaired executive functioning in adolescents.

Methods

A diverse, community sample of adolescents (N = 288; mean age = 16.33; 51.4% female; 59.0% African-American) completed assessments of height and weight, IL-6, depressive symptoms, and self-report/behavioral measures of executive functioning (selective attention, switching attention) and future orientation annually over 3 years. Adolescents experiencing acute illness or medical conditions that affect inflammation were excluded from analyses. Path analysis within a structural equation modeling framework simultaneously examined the concurrent and prospective relationships between BMI, IL-6, depressive symptoms, and the measures of cognitive functioning across three timepoints.

Results

Across all timepoints, higher BMI was prospectively associated with higher levels of IL-6 and depressive symptoms, while higher levels of IL-6 were associated with worse performance on three behavioral and self-report measures of cognitive functioning. Higher depressive symptoms also were prospectively associated with elevated IL-6 and both higher depressive symptoms and a higher BMI predicted worse future executive functioning via increased IL-6.

Conclusions

More severe depressive symptoms and increased BMI may disrupt executive functioning via elevated IL-6.

Keywords

Adolescencebody masscognitive dysfunctiondepressionexecutive functioninginflammationinterleukin-6obesity
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 4 , March 2020 , pp. 683 - 691
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Allott, K, Fisher, CA, Amminger, GP, Goodall, J and Hetrick, S (2016) Characterizing neurocognitive impairment in young people with major depression: state, trait, or scar? Brain and Behavior 6, e00527.CrossRefGoogle ScholarPubMed
Amaral, WZ, Krueger, RF, Ryff, CD and Coe, CL (2015) Genetic and environmental determinants of population variation in interleukin-6, its soluble receptor and C-reactive protein: insights from identical and fraternal twins. Brain, Behavior, and Immunity 49, 171–181.CrossRefGoogle ScholarPubMed
Au, B, Smith, KJ, Gariepy, G and Schmitz, N (2015) The longitudinal associations between C-reactive protein and depressive symptoms: evidence from the English Longitudinal Study of Ageing (ELSA). International Journal of Geriatric Psychiatry 30, 976–984.CrossRefGoogle Scholar
Banich, MT (2009) Executive function. The search for an integrated account. Current Directions in Psychological Science 18, 89–94.CrossRefGoogle Scholar
Baune, B, Ponath, G, Golledge, J and Varga, G (2008) Association between IL-8 cytokine and cognitive performance in an elderly general population – the MEMO-Study. Neurobiology of Aging 29, 937–944.CrossRefGoogle Scholar
Breen, EC, Reynolds, SM, Cox, C, Jacobson, LP, Magpantay, L, Mulder, CB, Dibben, O, Margolick, JB, Bream, JH, Sambrano, E, Martinez-Maza, O, Sinclair, E, Borrow, P, Landay, AL, Rinaldo, CR and Norris, PJ (2011) Multisite comparison of high-sensitivity multiplex cytokine assays. Clinical and Vaccine Immunology 18, 1229–1242.CrossRefGoogle ScholarPubMed
Burcusa, SL and Iacono, WG (2007) Risk for recurrence in depression. Clinical Psychology Review 27, 959–985.CrossRefGoogle ScholarPubMed
Carvalho, AF, Miskowiak, KK, Hyphantis, TN, Kohler, CA, Alves, GS, Bortolato, B, PM, GS, Machado-Vieira, R, Berk, M and McIntyre, RS (2014) Cognitive dysfunction in depression – pathophysiology and novel targets. CNS & Neurological Disorders Drug Targets 13, 1819–1835.CrossRefGoogle ScholarPubMed
Chang, HH, Lee, IH, Gean, PW, Lee, SY, Chi, MH, Yang, YK, Lu, RB and Chen, PS (2012) Treatment response and cognitive impairment in major depression: association with C-reactive protein. Brain Behavior and Immunity 26, 90–95.CrossRefGoogle ScholarPubMed
Chen, FF (2007) Sensitivity of goodness of fit indexes to lack of measurement invariance. Structural Equation Modeling: A Multidisciplinary Journal 14, 464–504.CrossRefGoogle Scholar
Cheung, GW and Rensvold, RB (2002) Evaluating goodness-of-fit indexes for testing measurement invariance. Structural Equation Modeling: A Multidisciplinary Journal 9, 233–255.CrossRefGoogle Scholar
Clark, LA and Watson, D (1991) Tripartite model of anxiety and depression: psychometric evidence and taxonomic implications. Journal of Abnormal Psychology 100 and 316.CrossRefGoogle ScholarPubMed
D'Argembeau, A, Ortoleva, C, Jumentier, S and Van der Linden, M (2010) Component processes underlying future thinking. Memory & Cognition 38, 809–819.CrossRefGoogle ScholarPubMed
Dantzer, R (2001) Cytokine-induced sickness behavior: where do we stand? Brain Behavior and Immunity 15, 7–24.CrossRefGoogle ScholarPubMed
de Wit, L, Luppino, F, van Straten, A, Penninx, B, Zitman, F and Cuijpers, P (2010) Depression and obesity: a meta-analysis of community-based studies. Psychiatry Research 178, 230–235.CrossRefGoogle ScholarPubMed
Diamond, A (2013) Executive functions. Annual Review of Psychology 64, 135–168.CrossRefGoogle ScholarPubMed
Duivis, HE, Vogelzangs, N, Kupper, N, de Jonge, P and Penninx, BW (2013) Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA). Psychoneuroendocrinology 38, 1573–1585.CrossRefGoogle Scholar
Esteban-Cornejo, I, Tejero-Gonzalez, CM, Sallis, JF and Veiga, OL (2015) Physical activity and cognition in adolescents: a systematic review. Journal of Science and Medicine in Sport 18, 534–539.CrossRefGoogle ScholarPubMed
Friedman, NP, Miyake, A, Young, SE, DeFries, JC, Corley, RP and Hewitt, JK (2008) Individual differences in executive functions are almost entirely genetic in origin. Journal of Experimental Psychology: General 137, 201.CrossRefGoogle ScholarPubMed
Goldsmith, DR, Haroon, E, Woolwine, BJ, Jung, MY, Wommack, EC, Harvey, PD, Treadway, MT, Felger, JC and Miller, AH (2016) Inflammatory markers are associated with decreased psychomotor speed in patients with major depressive disorder. Brain Behavior and Immunity 56, 281–288.CrossRefGoogle ScholarPubMed
Gotlib, IH, Lewinsohn, PM and Seeley, JR (1995) Symptoms versus a diagnosis of depression: differences in psychosocial functioning. Journal of Consulting and Clinical Psychology 63, 90.CrossRefGoogle ScholarPubMed
Grant, BF, Goldstein, RB, Saha, TD, Chou, SP, Jung, J, Zhang, H, Pickering, RP, Ruan, WJ, Smith, SM, Huang, B and Hasin, DS (2015) Epidemiology of DSM-5 alcohol use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry 72, 757–766.CrossRefGoogle ScholarPubMed
Grant, BF, Saha, TD, Ruan, WJ, Goldstein, RB, Chou, SP, Jung, J, Zhang, H, Smith, SM, Pickering, RP, Huang, B and Hasin, DS (2016) Epidemiology of DSM-5 drug use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions–III. JAMA Psychiatry 73, 39–47.CrossRefGoogle ScholarPubMed
Haapakoski, R, Mathieu, J, Ebmeier, KP, Alenius, H and Kivimäki, M (2015) Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain Behavior and Immunity 49, 206–215.CrossRefGoogle ScholarPubMed
Heringa, S, Van den Berg, E, Reijmer, Y, Nijpels, G, Stehouwer, C, Schalkwijk, C, Teerlink, T, Scheffer, P, van den Hurk, K and Kappelle, L (2014) Markers of low-grade inflammation and endothelial dysfunction are related to reduced information processing speed and executive functioning in an older population – the Hoorn study. Psychoneuroendocrinology 40, 108–118.CrossRefGoogle Scholar
Huang, YS, Guilleminault, C, Hwang, FM, Cheng, C, Lin, CH, Li, HY and Lee, LA (2016) Inflammatory cytokines in pediatric obstructive sleep apnea. Medicine 95, e4944.CrossRefGoogle ScholarPubMed
Jenny, NS, French, B, Arnold, AM, Strotmeyer, ES, Cushman, M, Chaves, PH, Ding, J, Fried, LP, Kritchevsky, SB, Rifkin, DE, Sarnak, MJ and Newman, AB (2012) Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars. The Journals of Gerontology: Series A 67, 970–976.CrossRefGoogle ScholarPubMed
Kessler, RC, Berglund, P, Demler, O, Jin, R, Koretz, D, Merikangas, KR, Rush, AJ, Walters, EE and Wang, PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289, 3095–3105.CrossRefGoogle Scholar
Kohler, CA, Freitas, TH, Maes, M, de Andrade, NQ, Liu, CS, Fernandes, BS, Stubbs, B, Solmi, M, Veronese, N, Herrmann, N, Raison, CL, Miller, BJ, Lanctot, KL and Carvalho, AF (2017) Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatrica Scandinavica 135, 373–387.CrossRefGoogle ScholarPubMed
Kovacs, M (1992) The Children's Depression Inventory. North Tonawanda, NY: Multi-Health Systems, Inc.Google Scholar
Krogh, J, Benros, ME, Jørgensen, MB, Vesterager, L, Elfving, B and Nordentoft, M (2014) The association between depressive symptoms, cognitive function, and inflammation in major depression. Brain Behavior and Immunity 35, 70–76.CrossRefGoogle ScholarPubMed
Laitala, VS, Kaprio, J, Koskenvuo, M, Raiha, I, Rinne, JO and Silventoinen, K (2011) Association and causal relationship of midlife obesity and related metabolic disorders with old age cognition. Current Alzheimer Research 8, 699–706.CrossRefGoogle ScholarPubMed
Levin, RL, Heller, W, Mohanty, A, Herrington, JD and Miller, GA (2007) Cognitive deficits in depression and functional specificity of regional brain activity. Cognitive Therapy and Research 31, 211–233.CrossRefGoogle Scholar
Li, X, Robertson, CM, Yu, X, Cheypesh, A, Dinu, IA and Li, J (2014) Early postoperative systemic inflammatory response is an important determinant for adverse 2-year neurodevelopment-associated outcomes after the Norwood procedure. The Journal of Thoracic and Cardiovascular Surgery 148, 202–206.CrossRefGoogle ScholarPubMed
Liang, J, Matheson, BE, Kaye, WH and Boutelle, KN (2014) Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents. International Journal of Obesity 38, 494–506.CrossRefGoogle ScholarPubMed
Mac Giollabhui, N, Olino, TM, Nielsen, J, Abramson, LY and Alloy, LB (2018) Is worse attention a risk factor for or a consequence of depression, or are worse attention and depression better accounted for by stress? A prospective test of three hypotheses. Clinical Psychological Science 7, 93–109.CrossRefGoogle Scholar
MacKenzie, LE, Uher, R and Pavlova, B (2018) Cognitive performance in first-degree relatives of individuals with vs without major depressive disorder: a meta-analysis. JAMA Psychiatry 76, 297–305.CrossRefGoogle Scholar
Maes, M, Meltzer, HY, Bosmans, E, Bergmans, R, Vandoolaeghe, E, Ranjan, R and Desnyder, R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. Journal of Affective Disorders 34, 301–309.CrossRefGoogle ScholarPubMed
Manly, T, Anderson, V, Nimmo-Smith, I, Turner, A, Watson, P and Robertson, IH (2001) The differential assessment of children's attention: The Test of Everyday Attention for Children (TEA-Ch), normative sample and ADHD performance. Journal of Child Psychology and Psychiatry 42, 1065–1081.CrossRefGoogle Scholar
McAfoose, J and Baune, BT (2009) Evidence for a cytokine model of cognitive function. Neuroscience and Biobehavioral Reviews 33, 355–366.CrossRefGoogle ScholarPubMed
Messay, B, Lim, A and Marsland, AL (2012) Current understanding of the bi-directional relationship of major depression with inflammation. Biology of Mood & Anxiety Disorders 2, 4.CrossRefGoogle ScholarPubMed
Michopoulos, V, Powers, A, Gillespie, CF, Ressler, KJ and Jovanovic, T (2017) Inflammation in fear-and anxiety-based disorders: PTSD, GAD, and beyond. Neuropsychopharmacology 42, 254.CrossRefGoogle ScholarPubMed
Misiak, B, Beszlej, JA, Kotowicz, K, Szewczuk-Boguslawska, M, Samochowiec, J, Kucharska-Mazur, J and Frydecka, D (2018) Cytokine alterations and cognitive impairment in major depressive disorder: from putative mechanisms to novel treatment targets. Progress in Neuro-Psychopharmacology & Biological Psychiatry 80, 177–188.CrossRefGoogle ScholarPubMed
Miyake, A and Friedman, NP (2012) The nature and organization of individual differences in executive functions: four general conclusions. Current Directions in Psychological Science 21, 8–14.CrossRefGoogle ScholarPubMed
Moriarity, DP, Mac Giollabhui, N, Ellman, LM, Klugman, J, Coe, C, Abramson, LY and Alloy, LB (In Press) Inflammatory biomarkers differentially predict change in depressive symptoms over time in male and female adolescents. Clinical Psychological Science.Google Scholar
Packwood, S, Hodgetts, HM and Tremblay, S (2011) A multiperspective approach to the conceptualization of executive functions. Journal of Clinical and Experimental Neuropsychology 33, 456–470.CrossRefGoogle ScholarPubMed
Pistell, PJ, Morrison, CD, Gupta, S, Knight, AG, Keller, JN, Ingram, DK and Bruce-Keller, AJ (2010) Cognitive impairment following high fat diet consumption is associated with brain inflammation. Journal of Neuroimmunology 219, 25–32.CrossRefGoogle ScholarPubMed
Preiss, K, Brennan, L and Clarke, D (2013) A systematic review of variables associated with the relationship between obesity and depression. Obesity Reviews 14, 906–918.CrossRefGoogle ScholarPubMed
Prickett, C, Brennan, L and Stolwyk, R (2015) Examining the relationship between obesity and cognitive function: a systematic literature review. Obesity Research & Clinical Practice 9, 93–113.CrossRefGoogle ScholarPubMed
Quek, YH, Tam, WWS, Zhang, MWB and Ho, RCM (2017) Exploring the association between childhood and adolescent obesity and depression: a meta-analysis. Obesity Reviews 18, 742–754.CrossRefGoogle ScholarPubMed
Raison, CL and Miller, AH (2011) Is depression an inflammatory disorder? Current Psychiatry Reports 13, 467–475.CrossRefGoogle ScholarPubMed
Reichenberg, A, Yirmiya, R, Schuld, A, Kraus, T, Haack, M, Morag, A and Pollmacher, T (2001) Cytokine-associated emotional and cognitive disturbances in humans. Archives of General Psychiatry 58, 445–452.CrossRefGoogle ScholarPubMed
Robertson, IH, Ward, T, Ridgeway, V and Nimmo-Smith, I (1994) The Test of Everyday Attention: TEA. Bury St. Edmunds, UK: Thames Valley Test Company.Google Scholar
Robertson, IH, Ward, T, Ridgeway, V and Nimmo-Smith, I (1996) The structure of normal human attention: The Test of Everyday Attention. Journal of the International Neuropsychological Society 2, 525–534.CrossRefGoogle ScholarPubMed
Rock, PL, Roiser, JP, Riedel, WJ and Blackwell, AD (2013) Cognitive impairment in depression: a systematic review and meta-analysis. Psychological Medicine 44, 1–12.Google ScholarPubMed
Schermelleh-Engel, K, Moosbrugger, H and Müller, H (2003) Evaluating the fit of structural equation models: tests of significance and descriptive goodness-of-fit measures. Methods of Psychological Research Online 8, 23–74.Google Scholar
Scult, MA, Paulli, AR, Mazure, ES, Moffitt, TE, Hariri, AR and Strauman, TJ (2017) The association between cognitive function and subsequent depression: a systematic review and meta-analysis. Psychological Medicine 47, 1–17.CrossRefGoogle ScholarPubMed
Shields, GS, Moons, WG and Slavich, GM (2017) Inflammation, self-regulation, and health: an immunologic model of self-regulatory failure. Perspectives on Psychological Science 12, 588–612.CrossRefGoogle ScholarPubMed
Singh-Manoux, A, Dugravot, A, Brunner, E, Kumari, M, Shipley, M, Elbaz, A and Kivimaki, M (2014) Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife. Neurology 83, 486–493.CrossRefGoogle ScholarPubMed
Slavich, GM and Irwin, MR (2014) From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychological Bulletin 140, 774–815.CrossRefGoogle ScholarPubMed
Smith, E, Hay, P, Campbell, L and Trollor, J (2011) A review of the association between obesity and cognitive function across the lifespan: implications for novel approaches to prevention and treatment. Obesity Reviews 12, 740–755.CrossRefGoogle ScholarPubMed
Snyder, HR (2013) Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychological Bulletin 139, 81–132.CrossRefGoogle ScholarPubMed
Sparkman, NL, Buchanan, JB, Heyen, JR, Chen, J, Beverly, JL and Johnson, RW (2006) Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers. Journal of Neuroscience 26, 10709–10716.CrossRefGoogle ScholarPubMed
Spyridaki, EC, Simos, P, Avgoustinaki, PD, Dermitzaki, E, Venihaki, M, Bardos, AN and Margioris, AN (2014) The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation. British Journal of Nutrition 112, 1724–1734.CrossRefGoogle ScholarPubMed
Spyridaki, EC, Avgoustinaki, PD and Margioris, AN (2016) Obesity, inflammation and cognition. Current Opinion in Behavioral Sciences 9, 169–175.CrossRefGoogle Scholar
Steinberg, L, Graham, S, O'Brien, L, Woolard, J, Cauffman, E and Banich, M (2009) Age differences in future orientation and delay discounting. Child Development 80, 28–44.CrossRefGoogle ScholarPubMed
Stewart, JC, Rand, KL, Muldoon, MF and Kamarck, TW (2009) A prospective evaluation of the directionality of the depression–inflammation relationship. Brain, Behavior, and Immunity 23, 936–944.CrossRefGoogle ScholarPubMed
Wagner, S, Müller, C, Helmreich, I, Huss, M and Tadić, A (2015) A meta-analysis of cognitive functions in children and adolescents with major depressive disorder. European Child & Adolescent Psychiatry 24, 5–19.CrossRefGoogle ScholarPubMed
Whiteford, HA, Degenhardt, L, Rehm, J, Baxter, AJ, Ferrari, AJ, Erskine, HE, Charlson, FJ, Norman, RE, Flaxman, AD, Johns, N, Burstein, R, Murray, CJL and Vos, T (2013) Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382, 1575–1586.CrossRefGoogle ScholarPubMed
Woo, YS, Rosenblat, JD, Kakar, R, Bahk, WM and McIntyre, RS (2016) Cognitive deficits as a mediator of poor occupational function in remitted major depressive disorder patients. Clinical Psychopharmacology and Neuroscience 14, 1–16.CrossRefGoogle ScholarPubMed
Yang, Y, Shields, GS, Guo, C and Liu, Y (2018) Executive function performance in obesity and overweight individuals: a meta-analysis and review. Neuroscience & Biobehavioral Reviews 84, 225–244.CrossRefGoogle ScholarPubMed
Zalli, A, Jovanova, O, Hoogendijk, WJ, Tiemeier, H and Carvalho, LA (2016) Low-grade inflammation predicts persistence of depressive symptoms. Psychopharmacology 233, 1669–1678.CrossRefGoogle ScholarPubMed
Supplementary material: File

Mac Giollabhui et al. supplementary material

Mac Giollabhui et al. supplementary material 1

Download Mac Giollabhui et al. supplementary material(File)
File 55.3 KB