2026 ECNP Congress

EP02-2023

Long-term electroconvulsive therapy exposure and brain aging: a prospective cohort study

Markus Hjorth — F. Stentebjerg Plesner, J. Macoveanu, M. Balslev Jørgensen, A. Jørgensen · Psychiatric Center Copenhagen, Copenhagen Affective Disorder Research Center, Copenhagen, Denmark

2026 ECNP Congress

Introduction

Psychiatric disorders are widely associated with accelerated biological aging, as indicated by epidemiological, clinical, and molecular markers [1]. This premature biological aging in psychiatric disease includes an accelerated structural brain aging [2]. Electroconvulsive therapy (ECT) is the most effective treatment for severe depression and several other psychiatric conditions. While it is well-established that ECT induces acute and transient structural changes in both cortical and subcortical regions, its long-term neurobiological effects remain largely unexplored. Investigating this is of significant clinical relevance given the broad use of ECT in modern psychiatric care. Many psychiatric patients choose not to receive ECT due to concern about potential long-term brain damage, although no scientific evidence supports that claim. Conversely, research suggests that ECT is associated with neurotrophic effects [3] and a reduced risk of developing dementia [4]. These findings indicate that ECT may actually counteract the accelerated aging process observed in psychiatric populations. In recent years, machine-learning algorithms applied to structural magnetic resonance imaging (MRI) have emerged as a tool for estimating biological brain age. A brain-predicted age difference (brain-PAD) can then be calculated by subtracting an individual’s chronological age from their estimated brain age. Studies utilising such MRI-based brain aging prediction models have indeed shown that psychiatric patients exhibit a higher brain-PAD compared to healthy controls [5].

Aims

The primary aim is characterizing biological brain aging in patients with long-term electroconvulsive therapy exposure. We hypothesise that patients receiving maintenance ECT will demonstrate a lower brain-PAD compared to clinically matched ECT-naive patients, but a higher brain-PAD than healthy controls.

Methods

This prospective cohort study leverages a population receiving maintenance ECT (MECT) as an ideal cohort for examining long-term neurobiological effects from ECT, as they provide extensive treatment exposure but without being in an acute illness phase. This population is therefore not expected to exhibit the transient structural changes associated with acute ECT, allowing for a more accurate evaluation of prolonged neurobiological effects. The study has a longitudinal design with three cohorts (n = 40 per group): 1) MECT patients, 2) ECT-naive patients clinically matched by age, sex, and clinical profile, and 3) healthy controls. Data is collected at baseline and at a six-month follow-up. Structural MRI (T1- and T2-weighted) is performed on a 3T scanner. Brain age is calculated using a validated brain-age prediction model (pyment) based on FreeSurfer-derived morphometric features from both the T1- and T2-weighted MRI. The primary outcome of the study is brain-PAD at baseline.

Results and Conclusions (ongoing study): Data collection is currently proceeding as planned. Data analysis is scheduled to start this summer. The conference poster will provide a comprehensive summary of the baseline cohort characteristics and a cross-sectional brain-PAD comparison at baseline. Furthermore, the poster will include a conclusion section based on the outcomes of the primary analyses.

References

  1. Jorgensen A, Baago IB, Rygner Z, Jorgensen MB, Andersen PK, Kessing LV, Poulsen HE: Association of Oxidative Stress-Induced Nucleic Acid Damage With Psychiatric Disorders in Adults: A Systematic Review and Meta-analysis. JAMA Psychiatry 2022 Sep 1;79(9):920-931.
  2. Seitz-Holland, Johanna, et al. “BrainAGE, Brain Health, and Mental Disorders: A Systematic Review.” Neuroscience and Biobehavioral Reviews, vol. 159, 2024, pp. 105581.
  3. Vanicek, T., Kranz, G.S., Vyssoki, B., Fugger, G., Komorowski, A., Hoflich, A., Saumer, G., Milovic, S., Lanzenberger, R., Eckert, A., Kasper, S., Frey, R., 2019. Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression. Brain stimulation 12, 1041-1050.
  4. Osler, M., Rozing, M.P., Christensen, G.T., Andersen, P.K., Jorgensen, M.B., 2018. Electroconvulsive therapy and risk of dementia in patients with affective disorders: a cohort study. Lancet Psychiatry 5, 348-356.
  5. Blake, Kimberly V., et al. “Advanced Brain Ageing in Adult Psychopathology: A Systematic Review and Meta-Analysis of Structural MRI Studies.” Journal of Psychiatric Research, vol. 157, 2023, pp. 180–91.