ABSTRACT
Objective: Despite the effectiveness of electroconvulsive therapy (ECT), patients and practitioners are often reluctant to start it due to the risk of transient cognitive side effects, particularly in older patients. Inflammatory processes may be associated with the occurrence of these effects. This study assessed whether inflammatory markers prior to ECT are associated with cognitive functioning in depressed patients treated with ECT.
Methods: Between 2011 and 2013, 97 older patients (mean [SD] age = 73.1 [8.1] years) with severe unipolar depression (according to DSM-IV) referred for ECT were included. Mini-Mental State Examination (MMSE) scores were used to determine cognitive functioning prior to, weekly during, and in the first week after a course of ECT. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were assessed prior to ECT.
Results: In fully adjusted models, there was an association between TNF-α and cognitive functioning (β = −1.05; 95% CI, −2.04 to −0.06; f2 = 0.06). An association was also found between baseline levels of IL-10 and TNF-α and lower MMSE scores during ECT (IL-10: β = −2.08; 95% CI, −3.22 to −0.95; TNF-α: β = −0.65; 95% CI, −1.07 to −0.22). In addition, an association was found between baseline CRP and lower MMSE scores directly after a course of ECT (β = −0.51; 95% CI, −0.93 to −0.09; f2 = 0.10). Associations with IL-6 did not reach significance.
Conclusions: This study suggests that inflammatory processes are associated with lower cognitive functioning prior to ECT and predispose for further cognitive dysfunction during and after a course of ECT.
Trial registration: ClinicalTrials.gov identifier: NCT02667353
Continue Reading...
Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.
References (77)
- Geduldig ET, Kellner CH. Electroconvulsive therapy in the elderly: new findings in geriatric depression. Curr Psychiatry Rep. 2016;18(4):40. PubMed CrossRef
- Rhee TG, Olfson M, Sint K, et al. Characterization of the quality of electroconvulsive therapy among older medicare beneficiaries. J Clin Psychiatry. 2020;81(4):19m13186. PubMed CrossRef
- Chakrabarti S, Grover S, Rajagopal R. Electroconvulsive therapy: a review of knowledge, experience and attitudes of patients concerning the treatment. World J Biol Psychiatry. 2010;11(3):525–537. PubMed CrossRef
- Obbels J, Verwijk E, Bouckaert F, et al. ECT-related anxiety: a systematic review. J ECT. 2017;33(4):229–236. PubMed CrossRef
- Kikuchi A, Yasui-Furukori N, Fujii A, et al. Identification of predictors of post-ictal delirium after electroconvulsive therapy. Psychiatry Clin Neurosci. 2009;63(2):180–185. PubMed CrossRef
- Reti IM, Krishnan A, Podlisky A, et al. Predictors of electroconvulsive therapy postictal delirium. Psychosomatics. 2014;55(3):272–279. PubMed CrossRef
- Fraser LM, O’Carroll RE, Ebmeier KP. The effect of electroconvulsive therapy on autobiographical memory: a systematic review. J ECT. 2008;24(1):10–17. PubMed CrossRef
- Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biol Psychiatry. 2010;68(6):568–577. PubMed CrossRef
- Andrade C, Arumugham SS, Thirthalli J. Adverse effects of electroconvulsive therapy. Psychiatr Clin North Am. 2016;39(3):513–530. PubMed CrossRef
- Kumar S, Mulsant BH, Liu AY, et al. Systematic review of cognitive effects of electroconvulsive therapy in late-life depression. Am J Geriatr Psychiatry. 2016;24(7):547–565. PubMed CrossRef
- Obbels J, Vansteelandt K, Verwijk E, et al. MMSE changes during and after ECT in late-life depression: a prospective study. Am J Geriatr Psychiatry. 2019;27(9):934–944. PubMed CrossRef
- Oudega ML, van Exel E, Wattjes MP, et al. White matter hyperintensities and cognitive impairment during electroconvulsive therapy in severely depressed elderly patients. Am J Geriatr Psychiatry. 2014;22(2):157–166. PubMed CrossRef
- Hausner L, Damian M, Sartorius A, et al. Efficacy and cognitive side effects of electroconvulsive therapy (ECT) in depressed elderly inpatients with coexisting mild cognitive impairment or dementia. J Clin Psychiatry. 2011;72(1):91–97. PubMed CrossRef
- Obbels J, Verwijk E, Vansteelandt K, et al. Long-term neurocognitive functioning after electroconvulsive therapy in patients with late-life depression. Acta Psychiatr Scand. 2018;138(3):223–231. PubMed CrossRef
- Verwijk E, Comijs HC, Kok RM, et al. Short- and long-term neurocognitive functioning after electroconvulsive therapy in depressed elderly: a prospective naturalistic study. Int Psychogeriatr. 2014;26(2):315–324. PubMed CrossRef
- Kumar DR, Han HK, Tiller J, et al. A brief measure for assessing patient perceptions of cognitive side effects after electroconvulsive therapy: the subjective assessment of memory impairment. J ECT. 2016;32(4):256–261. PubMed CrossRef
- Mignone S, Zufferey C, De Anstiss H. Family experiences of caring for relatives who have received electroconvulsive therapy (ECT). Aust Soc Work. 2018;71(1):86–97. CrossRef
- Sethi S, Williams RA. The family caregiving experience of outpatient ECT. J Am Psychiatr Nurses Assoc. 2003;9(6):187–194. CrossRef
- Choi J, Wang Y, Feng T, et al. Cognitive training to improve memory in individuals undergoing electroconvulsive therapy: negative findings. J Psychiatr Res. 2017;92:8–14. PubMed CrossRef
- Mohagheghi A, Arfaie A, Amiri S, et al. Preventive effect of liothyronine on electroconvulsive therapy-induced memory deficit in patients with major depressive disorder: a double-blind controlled clinical trial. BioMed Res Int. 2015;2015:503918. PubMed CrossRef
- Kellner CH, Adams DA, Benferhat A. Further improving the cognitive effect profile of electroconvulsive therapy (ECT): the case for studying carbamylated erythropoietin. Med Hypotheses. 2015;84(3):258–261. PubMed CrossRef
- Schmidt LS, Petersen JZ, Vinberg M, et al. Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial. Trials. 2018;19(1):234. PubMed CrossRef
- Henstra MJ, Jansma EP, van der Velde N, et al. Acetylcholinesterase inhibitors for electroconvulsive therapy-induced cognitive side effects: a systematic review. Int J Geriatr Psychiatry. 2017;32(5):522–531. PubMed CrossRef
- van Schaik AM, Rhebergen D, Henstra MJ, et al. Cognitive impairment and electroconvulsive therapy in geriatric depression, what could be the role of rivastigmine? a case series. Clin Pract. 2015;5(3):780. PubMed CrossRef
- Martin DM, Gálvez V, Loo CK. Predicting retrograde autobiographical memory changes following electroconvulsive therapy: Relationships between individual, treatment, and early clinical factors. Int J Neuropsychopharmacol. 2015;18(12):1–8. PubMed CrossRef
- van Oostrom I, van Eijndhoven P, Butterbrod E, et al. Decreased cognitive functioning after electroconvulsive therapy is related to increased hippocampal volume: exploring the role of brain plasticity. J ECT. 2018;34(2):117–123. PubMed CrossRef
- Socci C, Medda P, Toni C, et al. Electroconvulsive therapy and age: age-related clinical features and effectiveness in treatment resistant major depressive episode. J Affect Disord. 2018;227:627–632. PubMed CrossRef
- McCall WV, Reboussin DM, Weiner RD, et al. Titrated moderately suprathreshold vs fixed high-dose right unilateral electroconvulsive therapy: acute antidepressant and cognitive effects. Arch Gen Psychiatry. 2000;57(5):438–444. PubMed CrossRef
- Semkovska M, Landau S, Dunne R, et al. Bitemporal versus high-dose unilateral twice-weekly electroconvulsive therapy for depression (EFFECT-Dep): a pragmatic, randomized, non-inferiority trial. Am J Psychiatry. 2016;173(4):408–417. PubMed CrossRef
- Verwijk E, Comijs HC, Kok RM, et al. Neurocognitive effects after brief pulse and ultrabrief pulse unilateral electroconvulsive therapy for major depression: a review. J Affect Disord. 2012;140(3):233–243. PubMed CrossRef
- Pigot M, Andrade C, Loo C. Pharmacological attenuation of electroconvulsive therapy–induced cognitive deficits: theoretical background and clinical findings. J ECT. 2008;24(1):57–67. PubMed CrossRef
- Laroy M, Bouckaert F, Vansteelandt K, et al. Association between hippocampal volume change and change in memory following electroconvulsive therapy in late-life depression. Acta Psychiatr Scand. 2019;140(5):435–445. PubMed CrossRef
- Maclullich AMJ, Ferguson KJ, Miller T, et al. Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses. J Psychosom Res. 2008;65(3):229–238. PubMed CrossRef
- Maldonado JR. Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure. Int J Geriatr Psychiatry. 2018;33(11):1428–1457. PubMed CrossRef
- Liu X, Yu Y, Zhu S. Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): a meta-analysis of observational studies. PLoS One. 2018;13(4):e0195659. PubMed CrossRef
- Carlier A, Berkhof JG, Rozing M, et al. Inflammation and remission in older patients with depression treated with electroconvulsive therapy; findings from the MODECT study¶. J Affect Disord. 2019;256:509–516. PubMed CrossRef
- Kruse JL, Congdon E, Olmstead R, et al. Inflammation and improvement of depression following electroconvulsive therapy in treatment-resistant depression. J Clin Psychiatry. 2018;79(2):17m11597. PubMed CrossRef
- Dols A, Bouckaert F, Sienaert P, et al. Early- and late-onset depression in late life: a prospective study on clinical and structural brain characteristics and response to electroconvulsive therapy. Am J Geriatr Psychiatry. 2017;25(2):178–189. PubMed CrossRef
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Washington, DC: American Psychiatric Press; 1994.
- Amorim P, Lecrubier Y, Weiller E, et al. The Mini International Neuropsychiatric Interview. Eur Psychiatry. 1998;13(S4):198S.CrossRef
- Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198. PubMed CrossRef
- Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340(6):448–454. PubMed CrossRef
- Felger JC, Lotrich FE. Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience. 2013;246:199–229. PubMed CrossRef
- Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016;16(1):22–34. PubMed CrossRef
- Enache D, Pariante CM, Mondelli V. Markers of central inflammation in major depressive disorder: a systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun. 2019;81:24–40. PubMed CrossRef
- Gabryšová L, Howes A, Saraiva M, et al. The regulation of IL-10 expression. Curr Top Microbiol Immunol. 2014;380:157–190. PubMed
- Lobo-Silva D, Carriche GM, Castro AG, et al. Balancing the immune response in the brain: IL-10 and its regulation. J Neuroinflammation. 2016;13(1):297. PubMed CrossRef
- Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134(4):382–389. PubMed CrossRef
- van den Broek WW, Birkenhäger TK, de Boer D, et al. Guideline Electroconvulsive Therapy [Richtlijn Elektroconvulsietherapie]. Utrecht: de Tijdstroom; 2010.
- Campos MW, Serebrisky D, Castaldelli-Maia JM. Smoking and cognition. Curr Drug Abuse Rev. 2016;9(2):76–79. PubMed CrossRef
- Hassing LB. Light alcohol consumption does not protect cognitive function: a longitudinal prospective study. Front Aging Neurosci. 2018;10:81. PubMed CrossRef
- Hogenkamp PS, Benedict C, Sjögren P, et al. Late-life alcohol consumption and cognitive function in elderly men. Age (Dordr). 2014;36(1):243–249. PubMed CrossRef
- Osimo EF, Cardinal RN, Jones PB, et al. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: an electronic health record-based study. Psychoneuroendocrinology. 2018;91:226–234. PubMed CrossRef
- Qiu F, Liang C-L, Liu H, et al. Impacts of cigarette smoking on immune responsiveness: up and down or upside down? Oncotarget. 2017;8(1):268–284. PubMed CrossRef
- Szabo G. Alcohol’s contribution to compromised immunity. Alcohol Health Res World. 1997;21(1):30–41. PubMed
- Wang R, Fratiglioni L, Kalpouzos G, et al. Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age: s population-based study. Alzheimers Dement. 2017;13(3):247–256. PubMed CrossRef
- Cohen J. A power primer. Psychol Bull. 1992;112(1):155–159. PubMed CrossRef
- Perneger TV. What’s wrong with Bonferroni adjustments. BMJ. 1998;316(7139):1236–1238. PubMed CrossRef
- Simpson EEA, Hodkinson CF, Maylor EA, et al. Intracellular cytokine production and cognition in healthy older adults. Psychoneuroendocrinology. 2013;38(10):2196–2208. PubMed CrossRef
- Cezaretto A, Almeida-Pititto B, Alencar GP, et al; on the behalf of the ELSA-Brasil researchers. Utility of combined inflammatory biomarkers for the identification of cognitive dysfunction in non-diabetic participants of the ELSA-Brasil. Psychoneuroendocrinology. 2019;103:61–66. PubMed CrossRef
- Harrison SL, de Craen AJM, Kerse N, et al. Predicting risk of cognitive decline in very old adults using three models: the Framingham Stroke Risk Profile; the Cardiovascular Risk Factors, Aging, and Dementia Model; and oxi-inflammatory biomarkers. J Am Geriatr Soc. 2017;65(2):381–389. PubMed CrossRef
- Yang J, Fan C, Pan L, et al. C-reactive protein plays a marginal role in cognitive decline: a systematic review and meta-analysis. Int J Geriatr Psychiatry. 2015;30(2):156–165. PubMed CrossRef
- Misiak B, Beszłej JA, Kotowicz K, et al. Cytokine alterations and cognitive impairment in major depressive disorder: from putative mechanisms to novel treatment targets. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(pt C):177–188. PubMed CrossRef
- Walker KA, Gottesman RF, Wu A, et al. Systemic inflammation during midlife and cognitive change over 20 years: the ARIC Study. Neurology. 2019;92(11):e1256–e1267. PubMed
- Millett CE, Perez-Rodriguez M, Shanahan M, et al. C-reactive protein is associated with cognitive performance in a large cohort of euthymic patients with bipolar disorder [published online ahead of print November 19, 2019]. Mol Psychiatry. PubMed CrossRef
- Krogh J, Benros ME, Jørgensen MB, et al. The association between depressive symptoms, cognitive function, and inflammation in major depression. Brain Behav Immun. 2014;35:70–76. PubMed CrossRef
- Dik MG, Jonker C, Hack CE, et al. Serum inflammatory proteins and cognitive decline in older persons. Neurology. 2005;64(8):1371–1377. PubMed CrossRef
- Matsushima J, Kawashima T, Nabeta H, et al. Association of inflammatory biomarkers with depressive symptoms and cognitive decline in a community-dwelling healthy older sample: a 3-year follow-up study. J Affect Disord. 2015;173:9–14. PubMed CrossRef
- van den Biggelaar AHJJ, Gussekloo J, de Craen AJMM, et al. Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. Exp Gerontol. 2007;42(7):693–701. PubMed CrossRef
- Kargar M, Yousefi A, Mojtahedzadeh M, et al. Effects of celecoxib on inflammatory markers in bipolar patients undergoing electroconvulsive therapy: a placebo-controlled, double-blind, randomised study. Swiss Med Wkly. 2014;144:w13880. PubMed CrossRef
- Pendlebury ST, Cuthbertson FC, Welch SJV, et al. Underestimation of cognitive impairment by Mini-Mental State Examination versus the Montreal Cognitive Assessment in patients with transient ischemic attack and stroke: a population-based study. Stroke. 2010;41(6):1290–1293. PubMed CrossRef
- Houx PJ, Shepherd J, Blauw GJ, et al. Testing cognitive function in elderly populations: the PROSPER study.,PROspective Study of Pravastatin in the Elderly at Risk. J Neurol Neurosurg Psychiatry. 2002;73(4):385–389. PubMed CrossRef
- Moirand R, Galvao F, Lecompte M, et al. Usefulness of the Montreal Cognitive Assessment (MoCA) to monitor cognitive impairments in depressed patients receiving electroconvulsive therapy. Psychiatry Res. 2018;259:476–481. PubMed CrossRef
- Tielkes CEM, Comijs HC, Verwijk E, et al. The effects of ECT on cognitive functioning in the elderly: a review. Int J Geriatr Psychiatry. 2008;23(8):789–795. PubMed CrossRef
- Tierney MC, Szalai JP, Snow WG, et al. Domain specificity of the subtests of the Mini-Mental State Examination. Arch Neurol. 1997;54(6):713–716. PubMed CrossRef
- Gałecki P, Talarowska M, Anderson G, et al. Mechanisms underlying neurocognitive dysfunctions in recurrent major depression. Med Sci Monit. 2015;21:1535–1547. PubMed CrossRef
- Spaans HP, Verwijk E, Comijs HC, et al. Efficacy and cognitive side effects after brief pulse and ultrabrief pulse right unilateral electroconvulsive therapy for major depression: a randomized, double-blind, controlled study. J Clin Psychiatry. 2013;74(11):e1029–e1036. PubMed CrossRef
Members enjoy free PDF downloads on all articles.
Save
Cite
Already a member? Login
Advertisement
GAM ID: sidebar-top