Blood biomarkers of neuronal injury and astrocytic reactivity in electroconvulsive therapyShow others and affiliations
2025 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 30, no 4, p. 1601-1609Article in journal (Refereed) Published
Abstract [en]
Despite electroconvulsive therapy (ECT) being recognized as an effective treatment for major depressive episodes (MDE), its application is subject to controversy due to concerns over cognitive side effects. 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 = 99) underwent acute ECT. Blood was sampled just before (T0) and 30 min after (T1) the first ECT session, as well as just before the sixth session (T2; 48-72 h after the fifth session). Age- and sex-matched controls (N = 99) 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 < 0.001) and tau (p = 0.036) 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 -0.5% to 6.7%, p = 0.088) nor at T2 (mean change -3.2%, 95%CI -7.6% to 1.5%, p = 0.18). Similarly, no change in total tau was observed (mean change 3.7%, 95%CI -11.6% to 21.7%, p = 0.65). GFAP increased from T0 to T1 (mean change 20.3%, 95%CI 14.6 to 26.3%, p < 0.001), but not from T0 to T2 (mean change -0.7%, 95%CI -5.8% to 4.8%, p = 0.82). 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.
Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 30, no 4, p. 1601-1609
National Category
Neurosciences Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-116535DOI: 10.1038/s41380-024-02774-4ISI: 001328544200001PubMedID: 39363047Scopus ID: 2-s2.0-85205595687OAI: oai:DiVA.org:oru-116535DiVA, id: diva2:1903371
Funder
University of GothenburgSwedish Foundation for Strategic Research, KF10-0039Swedish Research Council, 2022-01643; 2022-01018; 2019-02397; 2017-00915; 2022-00732Fredrik och Ingrid Thurings Stiftelse, 2019-00478Wenner-Gren Foundations, SSv2019-0008EU, Horizon Europe, 101053962Stiftelsen Gamla TjänarinnorThe Swedish Brain Foundation, FO2022-0270; FO2017-0243; ALZ2022-0006EU, Horizon 2020, 860197Alzheimerfonden, AF-930351; AF-939721; AF-968270
Note
This work was supported by grants from the Swedish Foundation for Strategic Research (KF10-0039; ML), the Swedish Research Council (2022-01643; ML), Thurings stiftelse (2019-00478; RS), and by the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-965444; ML). RS was supported by a grant from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-942684). ML was supported by a grant from the Wenner-Gren foundation (SSv2019-0008). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (2022-01018 and 2019-02397), the European Union's Horizon Europe research and innovation program under grant agreement No 101053962, the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (201809-2016862), the AD Strategic Fund and the Alzheimer's Association (ADSF-21-831376-C, ADSF-21-831381-C, and ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen for Gamla Tjanarinnor, Hjarnfonden, Sweden (FO2022-0270), the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Program-Neurodegenerative Disease Research (JPND2021-00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). KB is supported by the Swedish Research Council (2017-00915 and 2022-00732), the Swedish Alzheimer Foundation (AF-930351, AF-939721 and AF-968270), Hjarnfonden, Sweden (FO2017-0243 and ALZ2022-0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG-715986 and ALFGBG-965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the Alzheimer's Association 2021 Zenith Award (ZEN-21-848495), and the Alzheimer's Association 2022-2025 Grant (SG-23-1038904 QC). We thank the study participants for their contribution to this research. We also thank the staff at ECT units throughout Sweden and the Swedish National Quality register for ECT (Q-ECT) for collection and sharing of data. A special thanks to the PREFECT project manager Anders Jureus, the PREFECT research nurses Marie Lundin, Birgitta Ohlander, Milka Krestelica, Radja Dawoud, Martina Wennberg, and the PREFECT data manager Bozenna Illiadou. The BBMRI.se and KI Biobank at Karolinska Institutet are acknowledged for professional biobank service.Open access funding provided by University of Gothenburg.
2024-10-042024-10-042025-03-24Bibliographically approved