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Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy.

ABSTRACT: BACKGROUND:Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. METHODS:Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice. RESULTS:The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069). CONCLUSIONS:The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.

SUBMITTER: Oltedal L

PROVIDER: S-EPMC6697556 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy.

Oltedal Leif L Narr Katherine L KL Abbott Christopher C Anand Amit A Argyelan Miklos M Bartsch Hauke H Dannlowski Udo U Dols Annemieke A van Eijndhoven Philip P Emsell Louise L Erchinger Vera Jane VJ Espinoza Randall R Hahn Tim T Hanson Lars G LG Hellemann Gerhard G Jorgensen Martin Balslev MB Kessler Ute U Oudega Mardien L ML Paulson Olaf B OB Redlich Ronny R Sienaert Pascal P Stek Max L ML Tendolkar Indira I Vandenbulcke Mathieu M Oedegaard Ketil J KJ Dale Anders M AM

Biological psychiatry 20180529 8

<h4>Background</h4>Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome.<h4>Methods</h4>Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. ...[more]

PMID: 30006199

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Project description:ImportanceKnowledge of the effectiveness of electroconvulsive therapy (ECT) in the treatment of manic episodes is based on clinical experience, but empirical evidence is scarce. Moreover, prognostic factors associated with response to ECT in patients with mania are poorly understood.ObjectiveTo investigate the response to ECT in patients with manic episodes.Design, setting, and participantsThis nationwide, register-based observational cohort study was conducted using data from patients admitted to psychiatric departments in Sweden that reported data to the Swedish National Quality Registry for ECT (Q-ECT). Patients admitted to any hospital in Sweden and receiving ECT for a manic episode between 2012 and 2019 were considered for inclusion (605 individuals). The outcome, Clinical Global Impression Improvement scale (CGI-I) score, was available in 571 patients. Data from several national registers were combined to determine clinical and sociodemographic factors. Analysis of data occurred from April through September 2021.ExposuresPatients treated with ECT for a mania were identified from the Q-ECT.Main outcomes and measuresResponse to ECT was defined by a CGI-I score of 1 (very much improved) or 2 (much improved). Remission was defined as a Clinical Global Impression Severity scale (CGI-S) score of 1 (reference range or not ill) or 2 (minimally ill) within 1 week after ECT. Univariate and multivariable regression models were used to investigate associations of sociodemographic factors, psychopharmacology, and comorbidities with response.ResultsAmong 571 patients with mania treated with ECT (211 [37.0%] men; median [IQR] age, 46 [31-59] years), 482 patients (84.4%) responded to ECT. Comorbid anxiety and obsessive-compulsive disorder (OCD) were associated with lower odds of response to ECT (adjusted odds ratio [aOR], 0.48; 95% CI, 0.25-0.90 and aOR, 0.17; 95% CI, 0.06-0.56, respectively). Patients who were markedly ill (aOR, 2.93; 95% CI, 1.23-7.00), severely ill (aOR, 2.60; 95% CI, 1.06-6.34), or among the most extremely ill (aOR, 7.94; 95% CI, 2.16-29.21) according to CGI-S score had higher odds of response than those with mild or moderate illness.Conclusions and relevanceThis study found that ECT was associated with improvement for mania in clinical settings, with especially high response rates in patients with severe illness and those without comorbid anxiety or OCD.

Project description:Electroconvulsive therapy (ECT) employs the elective induction of generalizes seizures as a potent treatment for severe psychiatric illness. As such, ECT provides an opportunity to rigorously study the recovery of consciousness, reconstitution of cognition, and electroencephalographic (EEG) activity following seizures. Fifteen patients with major depressive disorder refractory to pharmacologic therapy will be enrolled (Clinicaltrials.gov, NCT02761330). Adequate seizure duration will be confirmed following right unilateral ECT under etomidate anesthesia. Patients will then undergo randomization for the order in which they will receive three sequential treatments: etomidate + ECT, ketamine + ECT, and ketamine + sham ECT. Sessions will be repeated in the same sequence for a total of six treatments. Before each session, sensorimotor speed, working memory, and executive function will be assessed through a standardized cognitive test battery. After each treatment, the return of purposeful responsiveness to verbal command will be determined. At this point, serial cognitive assessments will begin using the same standardized test battery. The presence of delirium and changes in depression severity will also be ascertained. Sixty-four channel EEG will be acquired throughout baseline, ictal, and postictal epochs. Mixed-effects models will correlate the trajectories of cognitive recovery, clinical outcomes, and EEG metrics over time. This innovative research design will answer whether: (1) time to return of responsiveness will be prolonged with ketamine + ECT compared with ketamine + sham ECT; (2) time of restoration to baseline function in each cognitive domain will take longer after ketamine + ECT than after ketamine + sham ECT; (3) postictal delirium is associated with delayed restoration of baseline function in all cognitive domains; and (4) the sequence of reconstitution of cognitive domains following the three treatments in this study is similar to that occurring after an isoflurane general anesthetic (NCT01911195). Sub-studies will assess the relationships of cognitive recovery to the EEG preceding, concurrent, and following individual ECT sessions. Overall, this study will lead the development of biomarkers for tailoring the cogno-affective recovery of patients undergoing ECT.

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Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy.

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Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy.

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