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The pathophysiology of these side effects is not well understood. Here, we examined the effects of ECT on blood-based biomarkers of neuronal injury and astrocytic reactivity. Participants with a major depressive episode (N\u2009=\u200999) underwent acute ECT. Blood was sampled just before (T0) and 30\u2009min after (T1) the first ECT session, as well as just before the sixth session (T2; 48\u201372\u2009h after the fifth session). Age- and sex-matched controls (N\u2009=\u200999) were recruited from the general population. Serum concentrations of neurofilament light chain (NfL), total tau protein, and glial fibrillary acidic protein (GFAP) were measured with ultrasensitive single-molecule array assays. Utilizing generalized least squares regression, we compared baseline (T0) biomarker concentrations against those of our control group, and calculated the shifts in serum biomarker concentrations from baseline to immediately post-first ECT session (T1), and prior to the sixth session (T2). Baseline analysis revealed that serum levels of NfL (p\u2009&lt;\u20090.001) and tau (p\u2009=\u20090.036) were significantly elevated in ECT recipients compared with controls, whereas GFAP levels showed no significant difference. Relative to T0, serum NfL concentration neither changed at T1 (mean change 3.1%, 95%CI \u22120.5% to 6.7%, p\u2009=\u20090.088) nor at T2 (mean change \u22123.2%, 95%CI \u22127.6%\u00a0to\u00a01.5%, p\u2009=\u20090.18). Similarly, no change in total tau was observed (mean change 3.7%, 95%CI \u221211.6% to 21.7%, p\u2009=\u20090.65). GFAP increased from T0 to T1 (mean change 20.3%, 95%CI 14.6\u00a0to\u00a026.3%, p\u2009&lt;\u20090.001), but not from T0 to T2 (mean change \u22120.7%, 95%CI \u22125.8% to 4.8%, p\u2009=\u20090.82). In conclusion, our findings suggest that ECT induces a temporary increase in serum GFAP, possibly reflecting transient astrocytic activation. Importantly, we observed no indicators of neuronal damage or long-term elevation in any assessed biomarker.<\/jats:p>","DOI":"10.1038\/s41380-024-02774-4","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T16:02:21Z","timestamp":1727971341000},"page":"1601-1609","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Blood biomarkers of neuronal injury and astrocytic reactivity in electroconvulsive therapy"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-1532","authenticated-orcid":false,"given":"Robert","family":"Sigstr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6118-6054","authenticated-orcid":false,"given":"Andreas","family":"G\u00f6teson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Joas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"P\u00e5lsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benny","family":"Liberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7454-3065","authenticated-orcid":false,"given":"Axel","family":"Nordenskj\u00f6ld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-6451","authenticated-orcid":false,"given":"Mikael","family":"Land\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"2774_CR1","doi-asserted-by":"crossref","unstructured":"Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CH, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ. 2019;364:l1079.","DOI":"10.1136\/bmj.l1079"},{"key":"2774_CR2","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1017\/S003329172200085X","volume":"52","author":"CF Meechan","year":"2022","unstructured":"Meechan CF, Laws KR, Young AH, McLoughlin DM, Jauhar S. ECT is evidence-based \u2013 a commentary on depression: why drugs and electricity are not the answer. Psychol Med. 2022;52:1416\u20138.","journal-title":"Psychol Med"},{"key":"2774_CR3","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.biopsych.2010.06.009","volume":"68","author":"M Semkovska","year":"2010","unstructured":"Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biol psychiatry. 2010;68:568\u201377.","journal-title":"Biol psychiatry"},{"key":"2774_CR4","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1017\/S0033291714000658","volume":"44","author":"G Fernie","year":"2014","unstructured":"Fernie G, Bennett DM, Currie J, Perrin JS, Reid IC. Detecting objective and subjective cognitive effects of electroconvulsive therapy: intensity, duration and test utility in a large clinical sample. Psychol Med. 2014;44:2985\u201394.","journal-title":"Psychol Med"},{"key":"2774_CR5","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S2215-0366(18)30056-7","volume":"5","author":"M Osler","year":"2018","unstructured":"Osler M, Rozing MP, Christensen GT, Andersen PK, J\u00f8rgensen MB. Electroconvulsive therapy and risk of dementia in patients with affective disorders: a cohort study. Lancet Psychiatry. 2018;5:348\u201356.","journal-title":"Lancet Psychiatry"},{"key":"2774_CR6","doi-asserted-by":"crossref","DOI":"10.1016\/j.psyneuen.2019.104414","volume":"110","author":"A Carlier","year":"2019","unstructured":"Carlier A, Boers K, Veerhuis R, Bouckaert F, Sienaert P, Eikelenboom P, et al. S100 calcium-binding protein B in older patients with depression treated with electroconvulsive therapy. Psychoneuroendocrinology. 2019;110:104414.","journal-title":"Psychoneuroendocrinology"},{"key":"2774_CR7","doi-asserted-by":"crossref","unstructured":"Gbyl K, J\u00f8rgensen NR, Videbech P. Serum S100B protein after electroconvulsive therapy in patients with depression. Acta Neuropsychiatrica. 2022;34:269\u201375.","DOI":"10.1017\/neu.2022.8"},{"key":"2774_CR8","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00702-014-1228-9","volume":"121","author":"L Kranaster","year":"2014","unstructured":"Kranaster L, Janke C, Mindt S, Neumaier M, Sartorius A. Protein S-100 and neuron-specific enolase serum levels remain unaffected by electroconvulsive therapy in patients with depression. J Neural Transm. 2014;121:1411\u20135.","journal-title":"J Neural Transm"},{"key":"2774_CR9","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1136\/jnnp.71.3.394","volume":"71","author":"M Agelink","year":"2001","unstructured":"Agelink M, Andrich J, Postert T, W\u00fcrzinger U, Zeit T, Klotz P, et al. Relation between electroconvulsive therapy, cognitive side effects, neuron specific enolase, and protein S-100. J Neurol, Neurosurg Psychiatry. 2001;71:394\u20136.","journal-title":"J Neurol, Neurosurg Psychiatry"},{"key":"2774_CR10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.psychres.2009.01.027","volume":"177","author":"J Palmio","year":"2010","unstructured":"Palmio J, Huuhka M, Laine S, Huhtala H, Peltola J, Leinonen E, et al. 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RS reports that he has received honoraria from the Swedish Medical Products Agency outside the area of this research. EJ is currently employed at IQVIA, M\u00f6lndal, Sweden. KB reports that he has served as a consultant and at advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. HZ reports that he has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the submitted work. ML reports that he has received lecture honoraria from Lundbeck pharmaceutical outside the area of this research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}