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Prodi T, Pezzullo G, La Monica K, Priori A, Vismara M, Dell’Osso B, Benatti B. Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression in a Real-World Setting: Findings from a Cohort Study. Brain Sci 2024; 14:949. [PMID: 39335443 PMCID: PMC11430495 DOI: 10.3390/brainsci14090949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND/OBJECTIVES In the past two decades, significant advancements in neuromodulation techniques have occurred, such as transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). According to the assumption that repeated stimulation within a condensed timeframe can yield sustained efficacy, an accelerated protocol may be more effective in reducing time to response. With those premises, this study aimed to evaluate a sample of TRD patients treated with standard repetitive TMS (rTMS) and accelerated rTMS (arTMS). METHODS Nine subjects were treated with standard rTMS and 19 with arTMS. Psychometric assessment was made at the baseline and one week, one month, and three months after the treatment. A linear mixed-effect regression was performed along with other appropriate statistical analyses. RESULTS A significant improvement over time was observed for both depressive and cognitive symptoms. Moreover, considering the reduction in the Montgomery-Asberg Depression Rating Scale scores, a better treatment response was observed in subjects treated with arTMS (p < 0.05). CONCLUSIONS Our findings showed a significant difference between the two protocols in terms of clinical response. Although further studies are needed to confirm the superiority of arTMS, the better cost-effectiveness of this technique should be considered.
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Affiliation(s)
- Tiziano Prodi
- Department of Psychiatry, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (T.P.)
| | - Gabriele Pezzullo
- Department of Psychiatry, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (T.P.)
| | - Kevin La Monica
- Department of Psychiatry, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (T.P.)
| | - Alberto Priori
- “Aldo Ravelli” Center for Nanotechnology and Neurostimulation, University of Milan, 20122 Milan, Italy
- Department of Health Sciences, San Paolo Hospital, University of Milan, 20142 Milan, Italy
| | - Matteo Vismara
- Department of Psychiatry, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (T.P.)
| | - Bernardo Dell’Osso
- Department of Psychiatry, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (T.P.)
- “Aldo Ravelli” Center for Nanotechnology and Neurostimulation, University of Milan, 20122 Milan, Italy
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA
| | - Beatrice Benatti
- Department of Psychiatry, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (T.P.)
- “Aldo Ravelli” Center for Nanotechnology and Neurostimulation, University of Milan, 20122 Milan, Italy
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Liu Y, Yang J, Liu Y. Ketamine and electroconvulsive therapy for severe depression: A network meta-analysis of efficacy and safety. J Psychiatr Res 2024; 175:218-226. [PMID: 38744161 DOI: 10.1016/j.jpsychires.2024.05.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/21/2024] [Accepted: 05/08/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Ketamine, electroconvulsive therapy (ECT), and their combination are effective for treating severe depression, but few large-scale studies have compared these. METHODS We searched databases for randomized controlled trials (RCTs) using ketamine, ECT, ketamine + ECT, or placebo for severe depression. Standardized measures were efficacy outcomes. Risk of bias was assessed. Stata and ADDIS were used for network meta-analysis (NMA) comparing efficacy and adverse reactions post-treatment. This study was registered on PROSPERO (CRD42023476740). RESULTS 17 RCTs with 1370 patients were included. NMA showed ECT and ketamine improved Hamilton Depression Rating Scale (HDRS) versus placebo; other comparisons not significant. Rank probabilities showed highest probability for ECT, followed by ketamine + ECT, ketamine, placebo. No differences in Montgomery-Asberg Depression Rating Scale (MADRS); highest rank probability again for ECT, followed by ketamine + ECT, ketamine, placebo. CONCLUSIONS Analysis suggests ECT superior to ketamine and their combination for improving depressive severity, but individualized treatment selection warranted. Higher adverse reactions with ketamine + ECT need further study for optimized combined use.
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Affiliation(s)
- Yecun Liu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jiguo Yang
- School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China.
| | - Yuanxiang Liu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
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Menon SN, Torrico T, Luber B, Gindoff B, Cullins L, Regenold W, Lisanby SH. Educating the next generation of psychiatrists in the use of clinical neuromodulation therapies: what should all psychiatry residents know? Front Psychiatry 2024; 15:1397102. [PMID: 38812486 PMCID: PMC11133724 DOI: 10.3389/fpsyt.2024.1397102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 04/30/2024] [Indexed: 05/31/2024] Open
Abstract
A variety of neuromodulation treatments are available today and more are on the way, but are tomorrow's psychiatrists prepared to incorporate these tools into their patients' care plans? This article addresses the need for training in clinical neuromodulation for general psychiatry trainees. To ensure patient access to neuromodulation treatments, we believe that general psychiatrists should receive adequate education in a spectrum of neuromodulation modalities to identify potential candidates and integrate neuromodulation into their multidisciplinary care plans. We propose curricular development across the four FDA-cleared modalities currently available in psychiatric practice: electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). With a focus on psychiatry residency training, the article delineates core learning components for each neuromodulation technique. For each modality, we review the clinical training status, the respective FDA-cleared indications, mechanisms of action, clinical indications and contraindications, adverse effects, informed consent process, dosing considerations, and clinical management guidelines. The approach outlined in this article aims to contribute to the development of a well-rounded generation of psychiatry trainees with the capacity to navigate the growing field of neuromodulation. Whether or not a psychiatrist specializes in delivering neuromodulation therapies themselves, it is incumbent on all psychiatrists to be able to identify patients who should be referred to neuromodulation therapies, and to provide comprehensive patient care before, during and after clinical neuromodulation interventions to optimize outcomes and prevent relapse.
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Affiliation(s)
- Sahit N. Menon
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, United States
| | - Tyler Torrico
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, United States
| | - Bruce Luber
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, United States
| | - Brian Gindoff
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, United States
| | - Lisa Cullins
- Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, United States
| | - William Regenold
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, United States
| | - Sarah H. Lisanby
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, United States
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Belge JB, van Eijndhoven P, Mulders PCR. Mechanism of Action of ECT in Depression. Curr Top Behav Neurosci 2024; 66:279-295. [PMID: 37962811 DOI: 10.1007/7854_2023_450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Electroconvulsive therapy (ECT) remains the most potent antidepressant treatment available for patients with major depressive disorder (MDD). ECT is highly effective, achieving a response rate of 70-80% and a remission rate of 50-60% even in treatment-resistant patients. The underlying mechanisms of ECT are not fully understood, although several hypotheses have been proposed, including the monoamine hypothesis, anticonvulsive hypothesis, neuroplastic effects, and immunomodulatory properties. In this paper, we provide an overview of magnetic resonance imaging evidence that addresses the neuroplastic changes that occur after ECT at the human systems level and elaborate further on ECTs potent immunomodulatory properties. Despite a growing body of evidence that suggests ECT may normalize many of the structural and functional changes in the brain associated with severe depression, there is a lack of convergence between neurobiological changes and the robust clinical effects observed in depression. This may be due to sample sizes used in ECT studies being generally small and differences in data processing and analysis pipelines. Collaborations that acquire large datasets, such as the GEMRIC consortium, can help translate ECT's clinical efficacy into a better understanding of its mechanisms of action.
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Affiliation(s)
- Jean-Baptiste Belge
- Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium.
- Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
| | - Philip van Eijndhoven
- Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands
- Donders Institute for Brain, Cognition and Behavior, Centre for Medical Neuroscience, Nijmegen, The Netherlands
| | - Peter C R Mulders
- Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands
- Donders Institute for Brain, Cognition and Behavior, Centre for Medical Neuroscience, Nijmegen, The Netherlands
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Akhtar SMM, Saleem SZ, Rizvi SHA, Raja S, Asghar MS. Beyond the surface: analyzing etomidate and propofol as anesthetic agents in electroconvulsive therapy-A systematic review and meta-analysis of seizure duration outcomes. Front Neurol 2023; 14:1251882. [PMID: 37915381 PMCID: PMC10616260 DOI: 10.3389/fneur.2023.1251882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 09/13/2023] [Indexed: 11/03/2023] Open
Abstract
Background Electroconvulsive therapy (ECT) is a widely used treatment for severe psychiatric disorders such as schizophrenia, depression, and mania. The procedure involves applying brief electrical stimulation to induce a seizure, and anesthesia is used to ensure sedation and muscle relaxation. Finding the right anesthetic agent with minimal side effects, especially on seizure duration, is crucial for optimal outcomes because seizure duration is an important factor in the effectiveness of ECT, but the anesthetic agents used can affect it. Objective This systematic review and meta-analysis aimed to pool the results of all relevant studies comparing the two induction agents, etomidate and propofol, for motor and electroencephalogram (EEG) seizure duration outcomes. Methods A comprehensive literature search was conducted in the PubMed, Medline, and Cochrane Library databases to identify the relevant articles. The primary outcome measures were motor and EEG seizure durations. Statistical power was ensured by performing heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Standard mean difference and 95% confidence intervals were calculated for continuous outcomes, and a random-effects model was used. Results A total of 16 studies were included in this meta-analysis, comprising 7 randomized control trials (RCTs), 7 crossover trials, and 2 cohorts. The overall motor seizure duration was statistically significantly longer with etomidate than with propofol. The overall result for EEG seizure duration was also longer with the use of etomidate over propofol and was statistically significant. In addition, subgrouping was performed based on the study design for both outcomes, which showed insignificant results in the cohort's subgroup for both outcomes, while the RCTs and crossover subgroups supported the overall results. Heterogeneity was assessed through subgrouping and sensitivity analysis. Conclusion Our meta-analysis found that etomidate is superior to propofol in terms of motor and EEG seizure duration in ECT, implying potentially better efficacy. Hence, etomidate should be considered the preferred induction agent in ECT, but larger studies are needed to further validate our findings.
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Affiliation(s)
- Syed M. M. Akhtar
- Department of Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Syed Z. Saleem
- Department of Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Syed H. A. Rizvi
- Department of Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Sandesh Raja
- Department of Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
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de A Simoes Moreira D, Gauer LE, Teixeira G, Fonseca da Silva AC, Cavalcanti S, Quevedo J. Efficacy and adverse effects of ketamine versus electroconvulsive therapy for major depressive disorder: A systematic review and meta-analysis. J Affect Disord 2023; 330:227-238. [PMID: 36907464 PMCID: PMC10497186 DOI: 10.1016/j.jad.2023.02.152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 02/26/2023] [Accepted: 02/28/2023] [Indexed: 03/14/2023]
Abstract
BACKGROUND ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220). METHODS We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date. SELECTION CRITERIA randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD. RESULTS Eight studies met the inclusion criteria (of 2875 retrieved). Random-effects models comparing ketamine and ECT regarding the following outcomes were conducted: a) reduction of depressive symptoms severity through scales, g = -0.12, p = 0.68; b) response to therapy, RR = 0.89, p = 0.51; c) reported side-effects: dissociative symptoms, RR = 5.41, p = 0.06; nausea, RR = 0.73, p = 0.47; muscle pain, RR = 0.25, p = 0.02; and headache, RR = 0.39, p = 0.08. Influential & subgroup analyses were performed. LIMITATIONS Methodological issues with high risk of bias in some of the source material, reduced number of eligible studies with high in-between heterogeneity and small sample sizes. CONCLUSION Our study showed no evidence to support the superiority of ketamine over ECT for severity of depressive symptoms and response to therapy. Regarding side effects, there was a statistically significant decreased risk of muscle pain in patients treated with ketamine compared to ECT.
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Affiliation(s)
| | | | | | | | - Stefanie Cavalcanti
- Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, USA; Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, USA
| | - João Quevedo
- Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, USA; Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
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Hartnett S, Rex S, Sienaert P. Asystole During Electroconvulsive Therapy: Does Electrode Placement Matter? A Systematic Review. J ECT 2023; 39:3-9. [PMID: 35700970 DOI: 10.1097/yct.0000000000000863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT Asystole presenting at the start of electrical stimulus application during electroconvulsive therapy (ECT) is a relatively common occurrence. It is most likely caused by vagal nerve stimulation, affecting autonomic cardiac tone. This article reviews the effect of the electrode placement (EP) on the incidence and severity of bradycardia and asystole. A systematic literature review was conducted using the Embase and PubMed databases, up to September 2021, searching for studies evaluating the effect of EP on bradycardia and/or asystole during ECT. Nine case reports describing asystole in patients receiving ECT almost exclusively reported the association with bitemporal (BT) EP. One small descriptive study found no significant effect of EP on cardiac pauses. The results from 4 cohort studies, however, suggest that a right unilateral placement bears a higher risk for developing bradycardia and asystole than BT and bifrontal ECT. The available evidence suggests that right unilateral ECT holds a greater risk for the development of bradycardia and asystole than BT and bifrontal EP.
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Affiliation(s)
- Sophie Hartnett
- From the KU Leuven, Department of Neurosciences, Research Group Psychiatry, Neuropsychiatry, Academic Center for ECT and Neuromodulation (AcCENT), University Psychiatric Center KU Leuven, Kortenberg
| | | | - Pascal Sienaert
- From the KU Leuven, Department of Neurosciences, Research Group Psychiatry, Neuropsychiatry, Academic Center for ECT and Neuromodulation (AcCENT), University Psychiatric Center KU Leuven, Kortenberg
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Noda Y, Knyahnytska Y, Zomorrodi R, Downar J, Rajji TK, Daskalakis ZJ, Blumberger DM. Vagally Mediated Heart Rate Variability Is Associated With Executive Function Changes in Patients With Treatment-Resistant Depression Following Magnetic Seizure Therapy. Neuromodulation 2022; 25:1378-1386. [PMID: 32870549 DOI: 10.1111/ner.13262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/03/2020] [Accepted: 07/25/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Magnetic seizure therapy (MST) is a novel investigational brain stimulation modality for patients with treatment-resistant depression (TRD). MST is a potential alternative seizure-based treatment to electroconvulsive therapy (ECT), given that it may offer equivalent antidepressant efficacy, yet with a relative sparing of cognitive functioning. Heart rate variability (HRV) is a marker of central autonomic functioning. We aimed to explore the relationships among baseline HRV, age, clinical outcome, and executive function following MST, in patients with TRD. MATERIALS AND METHODS Eighty-eight TRD patients (55 females; 18-70 years) were enrolled and 48 patients completed a course of MST in an open-label study. Patients received MST treatments two to three times per week, using one of three stimulation frequencies (ie, 100 Hz, 50 Hz, or 25 Hz) at 100% stimulator output. Root mean square of the successive R-R differences (RMSSD), an index of HRV, was computed from a baseline electrocardiogram (ECG) recording. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D24) and the Quick Inventory of Depressive Symptomatology (QIDS16). Executive function was assessed using the Trail Making Test and the Mazes Test from the MATRICS battery. RESULTS Baseline RMSSD was correlated with baseline HAM-D24 (r = -0.340, p = 0.001) and baseline Mazes Test (r = 0.417, p = 0.0007) but not with baseline Trail Making Test. Furthermore, baseline RMSSD was not correlated with changes on the HAM-D24, QIDS16, or total scores on the Trail Making Test. However, there was a significant correlation between baseline RMSSD and improvement on the Mazes Test following MST (r = 0.502, p = 0.0004). CONCLUSIONS Since this is an open-label trial, the influence of the placebo effect cannot be excluded. However, our results suggest that baseline RMSSD may be a state-biomarker of depression and executive function impairment. Additionally, while baseline vagally mediated resting cardiac activity did not predict the outcome of depression, it may mediate executive function improvements following MST.
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Affiliation(s)
- Yoshihiro Noda
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Yuliya Knyahnytska
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Reza Zomorrodi
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Jonathan Downar
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada; MRI-Guided rTMS Clinic, University Health Network, Toronto, ON, Canada
| | - Tarek K Rajji
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Zafiris J Daskalakis
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Daniel M Blumberger
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
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Garg A, Pj P, Shirahatti B. Effect of Modified Bifrontotemporal Electroconvulsive Therapy on Executive Function in Patients With Psychiatric Illness: A Longitudinal Observational Study. J ECT 2022; 38:176-184. [PMID: 35220364 DOI: 10.1097/yct.0000000000000837] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The study was conducted to compare the pre-electroconvulsive therapy (ECT) and post-ECT status of the executive functions of patients and report any deficits found at long-term follow-up. The secondary objective of the study was to compare the performance at executive function tests after ECT with patient characteristics and ECT parameters. METHODOLOGY In a prospective longitudinal observational study, 50 patients in the age group of 18 to 65 years who were receiving modified bifrontotemporal ECT for the first time and admitted in psychiatry ward of a tertiary care hospital from July 2015 to June 2016 were assessed for executive functions using a neuropsychological battery consisting of digit span forward, digit span backward, spatial span forward, spatial span backward, phonemic verbal fluency test, semantic verbal fluency test, Stroop test, and Wisconsin Card Sorting Test, a day before ECT and then followed up at 3 and 6 months. RESULTS Patients' score improved on all the tests of executive function at 3-month follow-up and was significant for some tests. Improvement was sustained for all the tests 6 months after ECT. Number of years of formal education of patients before illness significantly influenced patients' performance on most of the executive function tests after ECT. Younger age of the patient positively influenced patients' performance on digit span forward and backwards and semantic verbal fluency. CONCLUSIONS There are no executive function deficits 3 to 6 months after brief pulse modified ECT with bilateral electrode placement. A higher premorbid education level is associated with better performance on executive functions after ECT.
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Affiliation(s)
- Ankita Garg
- From the Psychiatry Department, Lourdes Institute of Behavioural Sciences, Lourdes Hospital, Kochi, Kerala, India
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L’efficacité de l’eskétamine dans le trouble dépressif majeur résistant : une revue systématique de la littérature. Encephale 2022; 48:455-461. [DOI: 10.1016/j.encep.2021.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 11/29/2021] [Accepted: 12/09/2021] [Indexed: 11/22/2022]
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Acute Mania and Catatonia in a Teenager Successfully Treated with Electroconvulsive Therapy and Diagnosed with Turner Syndrome and Bipolar Disorder. Case Rep Psychiatry 2021; 2021:3371591. [PMID: 34956685 PMCID: PMC8709772 DOI: 10.1155/2021/3371591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 11/30/2021] [Accepted: 12/03/2021] [Indexed: 11/18/2022] Open
Abstract
Background Turner syndrome (TS) is an X-linked chromosomal abnormality with a global prevalence of 1/2000 live-born girls. The physiological symptoms of TS have been thoroughly characterized, but only a few studies have described associated psychiatric symptoms. We report a case of an adolescent girl who presented with acute mania with psychotic features and was successfully treated with electroconvulsive therapy (ECT). She was subsequently diagnosed with bipolar syndrome and TS. Case Presentation. A 17-year-old girl presented to us with manic symptoms, including disorganized speech, auditory hallucinations, and affect lability. Initially, she was treated with antipsychotics and benzodiazepines, whereby the positive affective symptoms declined. However, the psychotic symptoms progressed, and she developed a catatonic state. ECT was started 6 days after admission, with improvement after two treatments. When ECT was tapered after seven sessions, she relapsed, and the treatment was extended to twelve sessions, with successful outcome. Following discharge, she was diagnosed with TS with partial loss on one of the X-chromosomes (46X, del (X)(p21)), which might have contributed to the development of her sudden acute manic episode. Conclusions This case demonstrates for the first time that ECT may be a safe and efficient treatment strategy for acute mania in adolescents with concomitant TS and that severely affected adolescents may require a prolonged series with gradual tapering of ECT. The present case also demonstrates a possible association between TS and bipolar syndrome and that the clinical presentation of a manic episode in a patient with this comorbidity could be more complex and the treatment response slower.
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Karrouri R, Hammani Z, Benjelloun R, Otheman Y. Major depressive disorder: Validated treatments and future challenges. World J Clin Cases 2021; 9:9350-9367. [PMID: 34877271 PMCID: PMC8610877 DOI: 10.12998/wjcc.v9.i31.9350] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/02/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Depression is a prevalent psychiatric disorder that often leads to poor quality of life and impaired functioning. Treatment during the acute phase of a major depressive episode aims to help the patient reach a remission state and eventually return to their baseline level of functioning. Pharmacotherapy, especially selective serotonin reuptake inhibitors antidepressants, remains the most frequent option for treating depression during the acute phase, while other promising pharmacological options are still competing for the attention of practitioners. Depression-focused psychotherapy is the second most common option for helping patients overcome the acute phase, maintain remission, and prevent relapses. Electroconvulsive therapy is the most effective somatic therapy for depression in some specific situations; meanwhile, other methods have limits, and their specific indications are still being studied. Combining medications, psychotherapy, and somatic therapies remains the most effective way to manage resistant forms of depression.
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Affiliation(s)
- Rabie Karrouri
- Department of Psychiatry, Moulay Ismaïl Military Hospital, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30070, Morocco
| | - Zakaria Hammani
- Department of Psychiatry, Moulay Ismaïl Military Hospital, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30070, Morocco
| | - Roukaya Benjelloun
- Department of Psychiatry, Faculty of Medicine, Mohammed VI University of Health Sciences, Casablanca 20000, Morocco
| | - Yassine Otheman
- Department of Psychiatry, Moulay Ismaïl Military Hospital, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30070, Morocco
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Stippl A, Kirkgöze FN, Bajbouj M, Grimm S. Differential Effects of Electroconvulsive Therapy in the Treatment of Major Depressive Disorder. Neuropsychobiology 2021; 79:408-416. [PMID: 32344410 DOI: 10.1159/000505553] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 12/11/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS/METHODS Electroconvulsive therapy (ECT) is still one of the most potent treatments in the acute phase of major depressive disorder (MDD) and particularly applied in patients considered treatment resistant. However, despite the frequent and widespread use of ECT for >70 years, the exact neurobiological mechanisms underlying its efficacy remain unclear. The present review aims to describe differential antidepressant and cognitive effects of ECT as well as effects on markers of neural activity and connectivity, neurochemistry, and inflammation that might underlie the treatment response and remission. RESULTS Region- specific changes in brain function and volume along with changes in concentrations of neurotransmitters and neuroinflammatory cytokines might serve as potential biomarkers for ECT outcomes. CONCLUSIONS However, as current data is not consistent, future longitudinal investigations should combine modalities such as MRI, MR spectroscopy, and peripheral physiological measures to gain a deeper insight into interconnected time- and modality-specific changes in response to ECT.
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Affiliation(s)
- Anna Stippl
- Department of Psychiatry and Psychotherapy, Charité, University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Fatma Nur Kirkgöze
- Department of Psychiatry and Psychotherapy, Charité, University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Malek Bajbouj
- Department of Psychiatry and Psychotherapy, Charité, University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Simone Grimm
- Department of Psychiatry and Psychotherapy, Charité, University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany, .,MSB Medical School Berlin, Berlin, Germany, .,Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Psychiatric Hospital, Zurich, Switzerland,
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14
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Carstens L, Hartling C, Aust S, Domke AK, Stippl A, Spies J, Brakemeier EL, Bajbouj M, Grimm S. EffECTively Treating Depression: A Pilot Study Examining Manualized Group CBT as Follow-Up Treatment After ECT. Front Psychol 2021; 12:723977. [PMID: 34539527 PMCID: PMC8446269 DOI: 10.3389/fpsyg.2021.723977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 07/31/2021] [Indexed: 11/27/2022] Open
Abstract
Background: There is an urgent need for effective follow-up treatments after acute electroconvulsive therapy (ECT) in depressed patients. Preliminary evidence suggests psychotherapeutic interventions to be a feasible and efficacious follow-up treatment. However, there is a need for research on the long-term usefulness of such psychotherapeutic offers in a naturalistic setting that is more representative of routine clinical practice. Therefore, the aim of the current pilot study was to investigate the effects of a half-open continuous group cognitive behavioral therapy (CBT) with cognitive behavioral analysis system of psychotherapy elements as a follow-up treatment for all ECT patients, regardless of response status after ECT, on reducing depressive symptoms and promoting psychosocial functioning. Method: Group CBT was designed to support patients during the often-difficult transition from inpatient to outpatient treatment. In a non-controlled pilot trial, patients were offered 15weekly sessions of manualized group CBT (called EffECTiv 2.0). The Montgomery-Åsberg Depression Rating Scale was assessed as primary outcome; the Beck Depression Inventory, WHO Quality of Life Questionnaire–BREF, and the Cognitive Emotion Regulation Questionnaire were assessed as secondary outcomes. Measurements took place before individual group start, after individual group end, and 6months after individual group end. Results: During group CBT, Post-ECT symptom reduction was not only maintained but there was a tendency toward a further decrease in depression severity. This reduction could be sustained 6months after end of the group, regardless of response status after ECT treatment. Aspects of quality of life and emotion regulation strategies improved during group CBT, and these improvements were maintained 6months after the end of the group. Conclusion: Even though the interpretability of the results is limited by the small sample and the non-controlled design, they indicate that manualized group CBT with cognitive behavioral analysis system of psychotherapy elements might pose a recommendable follow-up treatment option after acute ECT for depressed patients, regardless of response status after ECT. This approach might not only help to further reduce depressive symptoms and prevent relapse, but also promote long-term psychosocial functioning by improving emotion regulation strategies and psychological quality of life and thus could be considered as a valuable addition to clinical routine after future validation.
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Affiliation(s)
- Luisa Carstens
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany
| | - Corinna Hartling
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany
| | - Sabine Aust
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany
| | - Ann-Kathrin Domke
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany
| | - Anna Stippl
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany
| | - Jan Spies
- Department for Military Mental Health, German Armed Forces Military Hospital Berlin, Berlin, Germany
| | - Eva-Lotta Brakemeier
- Department of Psychology, Universität Greifswald, Franz-Mehring-Straße, Greifswald, Germany
| | - Malek Bajbouj
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany
| | - Simone Grimm
- Berlin Institute of Health, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin, Germany.,Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.,Department of Psychology, MSB Medical School Berlin, Berlin, Germany
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15
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Rajpurohit V, Chaudhary K, Kishan R, Kumari K, Sethi P, Sharma A. Bi-Spectral Index-Guided Comparison of Propofol versus Etomidate for Induction in Electroconvulsive Therapy. Anesth Essays Res 2021; 14:504-509. [PMID: 34092866 PMCID: PMC8159030 DOI: 10.4103/aer.aer_92_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 10/21/2020] [Accepted: 10/24/2020] [Indexed: 01/26/2023] Open
Abstract
Background: Previous studies have compared varying doses of propofol and etomidate for electroconvulsive therapy (ECT) without monitoring the depth of anesthesia. Seizure duration may vary with the depth of anesthesia. Aim: This study aimed to compare the effects of bi-spectral index (BIS)-guided induction with propofol and etomidate on various parameters of ECT. Settings and Design: This was a prospective, randomized, double-blind study. Materials and Methods: Sixty patients undergoing ECT were randomly allocated to two groups. Group P received intravenous propofol 1–2 mg.kg −1 and Group E received etomidate 0.1–0.3 mg.kg −1 to attain a BIS of 40–60. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and BIS were recorded at various time points intraoperatively till 30 min following ECT. Seizure duration, recovery time, and adverse effects were also recorded. Statistical Analysis: Quantitative data were compared using unpaired t-test. Chi-square test or Fisher's exact test was used to compare categorical data. P < 0.05 was considered statistically significant. Results: The mean induction time and seizure duration were shorter (P < 0.001), and recovery time to obey commands was longer in Group P as compared to that of Group E (P = 0.031). HR, SBP, and DBP for 10 min after ECT had elevated more in Group E than that in Group P (P < 0.05). The incidence of myoclonus was higher in Group P compared to that of Group E (P = 0.012). Conclusion: During ECT, BIS-guided induction with propofol provides more stable hemodynamics than etomidate, but reduces induction time, seizure duration, and recovery time more as compared to that of etomidate.
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Affiliation(s)
- Vikas Rajpurohit
- Department of Anesthesiology, S N Medical College, Jodhpur, Rajasthan, India
| | - Kriti Chaudhary
- Department of Anesthesiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Rama Kishan
- Department of Orthopaedics, S N Medical College, Jodhpur, Rajasthan, India
| | - Kamlesh Kumari
- Department of Anesthesiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Priyanka Sethi
- Department of Anesthesiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Ankur Sharma
- Department of Anesthesiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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16
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Carstens L, Hartling C, Stippl A, Domke AK, Herrera-Mendelez AL, Aust S, Gärtner M, Bajbouj M, Grimm S. A symptom-based approach in predicting ECT outcome in depressed patients employing MADRS single items. Eur Arch Psychiatry Clin Neurosci 2021; 271:1275-1284. [PMID: 34269881 PMCID: PMC8429160 DOI: 10.1007/s00406-021-01301-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 07/04/2021] [Indexed: 11/04/2022]
Abstract
Establishing symptom-based predictors of electroconvulsive therapy (ECT) outcome seems promising, however, findings concerning the predictive value of distinct depressive symptoms or subtypes are limited; previous factor-analytic approaches based on the Montgomery-Åsberg Depression Rating Scale (MADRS) remained inconclusive, as proposed factors varied across samples. In this naturalistic study, we refrained from these previous factor-analytic approaches and examined the predictive value of MADRS single items and their change during the course of ECT concerning ECT outcome. We used logistic and linear regression models to analyze MADRS data routinely assessed at three time points in 96 depressed psychiatric inpatients over the course of ECT. Mean age was 53 years (SD 14.79), gender ratio was 58:38 (F:M), baseline MADRS score was M = 30.20 (SD 5.42). MADRS single items were strong predictors of ECT response, remission and overall symptom reduction, especially items 1 (apparent sadness), 2 (reported sadness) and 8 (inability to feel), assessing affective symptoms. Strongest effects were found for regression models including item 2 (reported sadness) with up to 80% correct prediction of ECT outcome. ROC analyses were performed to estimate the optimal cut-point for treatment response. MADRS single items during the course of ECT might pose simple, reliable, time- and cost-effective predictors of ECT outcome. More severe affective symptoms of depression at baseline and a stronger reduction of these affective symptoms during the course of ECT seem to be positively associated with ECT outcome. Precise cut-off values for clinical use were proposed. Generally, these findings underline the benefits of a symptom-based approach in depression research and treatment in addition to depression sum-scores and generalized diagnoses.
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Affiliation(s)
- Luisa Carstens
- Department of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
| | - Corinna Hartling
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Anna Stippl
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Ann-Kathrin Domke
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Ana Lucia Herrera-Mendelez
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Sabine Aust
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Matti Gärtner
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany ,grid.466457.20000 0004 1794 7698Department of Psychology, MSB Medical School Berlin, Rüdesheimer Str. 50, 14197 Berlin, Germany
| | - Malek Bajbouj
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Simone Grimm
- grid.484013.aDepartment of Psychiatry, Centre for Affective Neuroscience (CAN), Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Campus Benjamin, Franklin, Hindenburgdamm 30, 12203 Berlin, Germany ,grid.7400.30000 0004 1937 0650Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032 Zurich, Switzerland ,grid.466457.20000 0004 1794 7698Department of Psychology, MSB Medical School Berlin, Rüdesheimer Str. 50, 14197 Berlin, Germany
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17
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Gärtner M, Ghisu E, Herrera-Melendez AL, Koslowski M, Aust S, Asbach P, Otte C, Regen F, Heuser I, Borgwardt K, Grimm S, Bajbouj M. Using routine MRI data of depressed patients to predict individual responses to electroconvulsive therapy. Exp Neurol 2020; 335:113505. [PMID: 33068570 DOI: 10.1016/j.expneurol.2020.113505] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/07/2020] [Accepted: 10/07/2020] [Indexed: 12/30/2022]
Abstract
Electroconvulsive therapy (ECT) is one of the most effective treatments in cases of severe and treatment resistant major depression. 60-80% of patients respond to ECT, but the procedure is demanding and robust prediction of ECT responses would be of great clinical value. Predictions based on neuroimaging data have recently come into focus, but still face methodological and practical limitations that are hampering the translation into clinical practice. In this retrospective study, we investigated the feasibility of ECT response prediction using structural magnetic resonance imaging (sMRI) data that was collected during ECT routine examinations. We applied machine learning techniques to predict individual treatment outcomes in a cohort of N = 71 ECT patients, N = 39 of which responded to the treatment. SMRI-based classification of ECT responders and non-responders reached an accuracy of 69% (sensitivity: 67%; specificity: 72%). Classification on additionally investigated clinical variables had no predictive power. Since dichotomisation of patients into ECT responders and non-responders is debatable due to many patients only showing a partial response, we additionally performed a post-hoc regression-based prediction analysis on continuous symptom improvements. This analysis yielded a significant relationship between true and predicted treatment outcomes and might be a promising alternative to dichotomization of patients. Based on our results, we argue that the prediction of individual ECT responses based on routine sMRI holds promise to overcome important limitations that are currently hampering the translation of such treatment biomarkers into everyday clinical practice. Finally, we discuss how the results of such predictive data analysis could best support the clinician's decision on whether a patient should be treated with ECT.
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Affiliation(s)
- Matti Gärtner
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; MSB - Medical School Berlin, Rüdesheimer Str. 50, 14197 Berlin.
| | - Elisabetta Ghisu
- Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, Switzerland
| | - Ana Lucia Herrera-Melendez
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Michael Koslowski
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany
| | - Sabine Aust
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Patrick Asbach
- Charité - Universitätsmedizin Berlin, Department of Radiology, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Christian Otte
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Francesca Regen
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Isabella Heuser
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Karsten Borgwardt
- Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, 4058, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, Switzerland
| | - Simone Grimm
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; MSB - Medical School Berlin, Rüdesheimer Str. 50, 14197 Berlin
| | - Malek Bajbouj
- Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
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18
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Kotsaki K, Diamantis A, Magiorkinis E. Ugo Cerletti (1877-1963): An Early Italian Father of Electroshock and a Pioneer in Many Other Ways. Neuroscientist 2020; 27:454-462. [PMID: 33023392 DOI: 10.1177/1073858420958381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This article provides a biographical review of the life and the professional achievements of the Italian doctor Ugo Cerletti and an introduction on electroshock. Throughout his medical career, he travelled and studied in many countries all over the world. Building upon his systematic and comprehensive analysis of mental diseases, Cerletti introduced electroshock, which, at his time, was a novel therapeutic method. The main beneficial feature of electroshock was that it ameliorated refractory mental illnesses such as depression, mania, and schizophrenia. Additionally, Cerletti filmed the first scientific movie on electroshock. Furthermore, Cerletti left great lessons in the area of dementia, by proving the interaction between spirochaetes and progressive paralysis and exploring the causes of inflammation in the syphilitic brain. Cerletti was the first to announce the theory of acroagonines. Cerletti also made early discoveries on perivascular corpuscles, a discovery of such importance that the perivascular corpuscles are named corpuscles of Cerletti. Outside of the medical realm, Cerletti invented a new type of gun, and produced an early medical documentary. Cerletti received many national and international distinctions and awards. He died in 1963 at the age of 86.
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Affiliation(s)
- Konstantina Kotsaki
- Office for the Study of History of Hellenic Naval Medicine, Naval Hospital of Athens, Athens, Attiki, Greece
| | - Aristidis Diamantis
- Office for the Study of History of Hellenic Naval Medicine, Naval Hospital of Athens, Athens, Attiki, Greece
| | - Emmanouil Magiorkinis
- Office for the Study of History of Hellenic Naval Medicine, Naval Hospital of Athens, Athens, Attiki, Greece.,Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Athens, Attiki, Greece.,Department of Laboratory Haematology, General Hospital for Chest Diseases "Sotiria," Athens, Attiki, Greece
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19
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Goldfarb S, Fainstein N, Ben-Hur T. Electroconvulsive stimulation attenuates chronic neuroinflammation. JCI Insight 2020; 5:137028. [PMID: 32780728 PMCID: PMC7526446 DOI: 10.1172/jci.insight.137028] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 07/29/2020] [Indexed: 12/11/2022] Open
Abstract
Electroconvulsive therapy is highly effective in resistant depression by unknown mechanisms. Microglial toxicity was suggested to mediate depression and plays key roles in neuroinflammatory and degenerative diseases, where there is critical shortage in therapies. We examined the effects of electroconvulsive seizures (ECS) on chronic neuroinflammation and microglial neurotoxicity. Electric brain stimulation inducing full tonic-clonic seizures during chronic relapsing-progressive experimental autoimmune encephalomyelitis (EAE) reduced spinal immune cell infiltration, reduced myelin and axonal loss, and prevented clinical deterioration. Using the transfer EAE model, we examined the effect of ECS on systemic immune response in donor mice versus ECS effect on CNS innate immune activity in recipient mice. ECS did not affect encephalitogenicity of systemic T cells, but it targeted the CNS directly to inhibit T cell-induced neuroinflammation. In vivo and ex vivo assays indicated that ECS suppressed microglial neurotoxicity by reducing inducible NOS expression, nitric oxide, and reactive oxygen species (ROS) production, and by reducing CNS oxidative stress. Microglia from ECS-treated EAE mice expressed less T cell stimulatory and chemoattractant factors. Our findings indicate that electroconvulsive therapy targets the CNS innate immune system to reduce neuroinflammation by attenuating microglial neurotoxicity. These findings signify a potentially novel therapeutic approach for chronic neuroinflammatory, neuropsychiatric, and neurodegenerative diseases.
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20
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Basso L, Bönke L, Aust S, Gärtner M, Heuser-Collier I, Otte C, Wingenfeld K, Bajbouj M, Grimm S. Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients. J Psychiatr Res 2020; 123:1-8. [PMID: 31981856 DOI: 10.1016/j.jpsychires.2020.01.002] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 01/13/2020] [Accepted: 01/13/2020] [Indexed: 01/16/2023]
Abstract
BACKGROUND While electroconvulsive therapy (ECT) is considered the gold standard for acute treatment of patients with otherwise treatment-resistant depression, ketamine has recently emerged as a fast-acting treatment alternative for these patients. Efficacy and onset of action are currently among the main factors that influence clinical decision making, however, the effect of these treatments on cognitive functions should also be a crucial point, given that cognitive impairment in depression is strongly related to disease burden and functional recovery. ECT is known to induce transient cognitive impairment, while little is known about ketamine's impact on cognition. This study therefore aims to compare ECT and serial ketamine administration not only with regard to their antidepressant efficacy but also to acute neurocognitive effects. METHODS Fifty patients suffering from depression were treated with either serial ketamine infusions or ECT. Depression severity and cognitive functions were assessed before, during, and after treatment. RESULTS ECT and ketamine administration were equally effective, however, the antidepressant effects of ketamine occurred faster. Ketamine improved neurocognitive functioning, especially attention and executive functions, whereas ECT was related to a small overall decrease in cognitive performance. CONCLUSIONS Due to its pro-cognitive effects and faster antidepressant effect, serial ketamine administration might be a more favorable short-term treatment option than ECT. LIMITATIONS As this research employed a naturalistic study design, patients were not systematically randomized, there was no control group and patients received concurrent and partially changing medications during treatment. CLINICAL TRIALS REGISTRATION Functional and Metabolic Changes in the Course of Antidepressive Treatment, https://clinicaltrials.gov/ct2/show/NCT02099630, NCT02099630.
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Affiliation(s)
- Laura Basso
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland
| | - Luisa Bönke
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
| | - Sabine Aust
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Matti Gärtner
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Isabella Heuser-Collier
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Christian Otte
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Katja Wingenfeld
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Malek Bajbouj
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Simone Grimm
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032, Zurich, Switzerland; Department of Psychology, MSB Medical School Berlin, Calandrellistr. 1-9, 12247, Berlin, Germany
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21
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Poon CH, Chan YS, Fung ML, Lim LW. Memory and neuromodulation: A perspective of DNA methylation. Neurosci Biobehav Rev 2019; 111:57-68. [PMID: 31846654 DOI: 10.1016/j.neubiorev.2019.12.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 11/05/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023]
Abstract
Neuromodulation techniques have shown promising efficacy on memory function and understanding the epigenetic mechanisms contributing to these processes would shed light on the molecular outcomes essential for cognition. In this review, we highlight some epigenetic mechanisms underlying neuromodulation and regulatory effects of neuronal activity-induced DNA methylation on genes that are highly involved in memory formation. Next, we examine the evidence to support DNA methyltransferase 3a, methyl-CpG binding protein 2, and DNA demethylase as possible memory modulation targets. Finally, we report the recent developments in the field of neuromodulation and explore the potential of these techniques for future neuroepigenetic research.
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Affiliation(s)
- Chi Him Poon
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ying-Shing Chan
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Man Lung Fung
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Lee Wei Lim
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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Réus GZ, de Moura AB, Borba LA, Abelaira HM, Quevedo J. Strategies for Treatment-Resistant Depression: Lessons Learned from Animal Models. MOLECULAR NEUROPSYCHIATRY 2019; 5:178-189. [PMID: 31768371 PMCID: PMC6873047 DOI: 10.1159/000500324] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 04/11/2019] [Indexed: 12/18/2022]
Abstract
Around 300 million individuals are affected by major depressive disorder (MDD) in the world. Despite this high number of affected individuals, more than 50% of patients do not respond to antidepressants approved to treat MDD. Patients with MDD that do not respond to 2 or more first-line antidepressant treatments are considered to have treatment-resistant depression (TRD). Animal models of depression are important tools to better understand the pathophysiology of MDD as well as to help in the development of novel and fast antidepressants for TRD patients. This review will emphasize some discovery strategies for TRD from studies on animal models, including, antagonists of N-methyl-D-aspartate (NMDA) receptor (ketamine and memantine), electroconvulsive therapy (ECT), lithium, minocycline, quetiapine, and deep brain stimulation. Animal models of depression are not sufficient to represent all the traits of TRD, but they greatly aid in understanding the mechanism by which therapies that work for TRD exert antidepressant effects. Interestingly, these innovative therapies have mechanisms of action different from those of classic antidepressants. These effects are mainly related to the regulation of neurotransmitter activity, including general glutamate and increased connectivity, synaptic capacity, and neuroplasticity.
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Affiliation(s)
- Gislaine Zilli Réus
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
| | - Airam Barbosa de Moura
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
| | - Laura Araújo Borba
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
| | - Helena Mendes Abelaira
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
| | - João Quevedo
- Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, Brazil
- Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
- Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
- Neuroscience Graduate Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA
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23
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Increased oxidation of RNA despite reduced mitochondrial respiration after chronic electroconvulsive stimulation of rat brain tissue. Neurosci Lett 2019; 690:1-5. [DOI: 10.1016/j.neulet.2018.09.061] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 09/09/2018] [Accepted: 09/28/2018] [Indexed: 12/11/2022]
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A Blind Module Identification Approach for Predicting Effective Connectivity Within Brain Dynamical Subnetworks. Brain Topogr 2018; 32:28-65. [PMID: 30076488 DOI: 10.1007/s10548-018-0666-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 07/28/2018] [Indexed: 10/28/2022]
Abstract
Model-based network discovery measures, such as the brain effective connectivity, require fitting of generative process models to measurements obtained from key areas across the network. For distributed dynamic phenomena, such as generalized seizures and slow-wave sleep, studying effective connectivity from real-time recordings is significantly complicated since (i) outputs from only a subnetwork can be practically measured, and (ii) exogenous subnetwork inputs are unobservable. Model fitting, therefore, constitutes a challenging blind module identification or model inversion problem for finding both the parameters and the many unknown inputs of the subnetwork. We herein propose a novel estimation framework for identifying nonlinear dynamic subnetworks in the case of slowly-varying, otherwise unknown local inputs. Starting with approximate predictions obtained using Cubature Kalman filtering, residuals of local output predictions are utilized to improve upon local input estimates. The algorithm performance is tested on both simulated and clinical EEG of induced seizures under electroconvulsive therapy (ECT). For the simulated network, the algorithm significantly boosted the estimation accuracy for inputs and connections from noisy EEG. For the clinical data, the algorithm predicted increased subnetwork inputs during the pre-stimulus anesthesia condition. Importantly, it predicted an increased frontocentral connectivity during the generalized seizure that is commensurate with electrode placement and that corroborates the clinical hypothesis of increased frontal focality of therapeutic ECT seizures. The proposed framework can be extended to account for several input configurations and can in principle be applied to study effective connectivity within brain subnetworks defined at the microscale (cortical lamina interaction) or at the macroscale (sensory integration).
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25
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Young KD, Zotev V, Phillips R, Misaki M, Drevets WC, Bodurka J. Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review. Psychiatry Clin Neurosci 2018; 72:466-481. [PMID: 29687527 PMCID: PMC6035103 DOI: 10.1111/pcn.12665] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/19/2018] [Indexed: 12/13/2022]
Abstract
Advances in imaging technologies have allowed for the analysis of functional magnetic resonance imaging data in real-time (rtfMRI), leading to the development of neurofeedback (nf) training. This rtfMRI-nf training utilizes functional magnetic resonance imaging (fMRI) tomographic localization capacity to allow a person to see and regulate the localized hemodynamic signal from his or her own brain. In this review, we summarize the results of several studies that have developed and applied neurofeedback training to healthy and depressed individuals with the amygdala as the neurofeedback target and the goal to increase the hemodynamic response during positive autobiographical memory recall. We review these studies and highlight some of the challenges and advances in developing an rtfMRI-nf paradigm for broader use in psychiatric populations. The work described focuses on our line of research aiming to develop the rtfMRI-nf into an intervention, and includes a discussion of the selection of a region of interest for feedback, selecting a control condition, behavioral and cognitive effects of training, and predicting which participants are most likely to respond well to training. While the results of these studies are encouraging and suggest the clinical potential of amygdala rtfMRI-nf in alleviating symptoms of major depressive disorder, larger studies are warranted to confirm its efficacy.
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Affiliation(s)
- Kymberly D. Young
- Laureate Institute for Brain Research, Tulsa, OK
- University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Vadim Zotev
- Laureate Institute for Brain Research, Tulsa, OK
| | | | | | - Wayne C. Drevets
- Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ
| | - Jerzy Bodurka
- Laureate Institute for Brain Research, Tulsa, OK
- Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK
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26
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Transient aphasia after right-unilateral ultrabrief electroconvulsive therapy: A case report. Brain Stimul 2018; 11:1203-1204. [PMID: 29945792 DOI: 10.1016/j.brs.2018.06.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 06/06/2018] [Accepted: 06/16/2018] [Indexed: 11/24/2022] Open
Abstract
A brief period of aphasia is an extremely rare and likely underreported adverse effect of electroconvulsive therapy. Clinical studies that have described this phenomenon are scarce and its prevalence is unknown. We present a unique case of a 35-year old woman, who underwent an outpatient ECT session at our department, followed by a short span of aphasic symptoms, the extent of which were monitored clinically and via the czech version of the Minnesota aphasia screening test.
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27
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Radman T, Lisanby SH. New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST). Int Rev Psychiatry 2017; 29:63-78. [PMID: 28430533 DOI: 10.1080/09540261.2017.1304898] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.
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Affiliation(s)
- Thomas Radman
- a National Institute of Mental Health , Bethesda , MD , USA
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28
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Ryan KM, Glaviano A, O'Donovan SM, Kolshus E, Dunne R, Kavanagh A, Jelovac A, Noone M, Tucker GM, Dunn MJ, McLoughlin DM. Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study. Transl Psychiatry 2017; 7:e1073. [PMID: 28350398 PMCID: PMC5404616 DOI: 10.1038/tp.2017.51] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/15/2017] [Accepted: 02/01/2017] [Indexed: 12/12/2022] Open
Abstract
Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.
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Affiliation(s)
- K M Ryan
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland,Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland
| | - A Glaviano
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
| | - S M O'Donovan
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
| | - E Kolshus
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland,Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland
| | - R Dunne
- Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland
| | - A Kavanagh
- Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland
| | - A Jelovac
- Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland
| | - M Noone
- Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland
| | - G M Tucker
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
| | - M J Dunn
- Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - D M McLoughlin
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland,Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland,Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, James's Street, Dublin 8, Ireland. E-mail:
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29
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Bilateral ECT induces bilateral increases in regional cortical thickness. Transl Psychiatry 2016; 6:e874. [PMID: 27552587 PMCID: PMC5022085 DOI: 10.1038/tp.2016.139] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Revised: 05/29/2016] [Accepted: 06/09/2016] [Indexed: 02/07/2023] Open
Abstract
Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.
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30
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Benson-Martin JJ, Stein DJ, Baldwin DS, Domschke K. Genetic mechanisms of electroconvulsive therapy response in depression. Hum Psychopharmacol 2016; 31:247-51. [PMID: 27062668 DOI: 10.1002/hup.2531] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2015] [Accepted: 02/20/2016] [Indexed: 01/28/2023]
Abstract
Electroconvulsive therapy (ECT) is known to be one of the most effective treatments for managing depression and other severe mental illnesses. Nevertheless, the exact mechanisms underlying response to ECT remain uncertain. This mini-review presents clinical findings regarding the role of genetic factors in the aetiology of the ECT response. Studies on the role of variation in the catechol-O-methyltransferase (COMT) gene; other dopamine-, serotonin-, and G-protein-related genes; brain-derived neurotrophic factor (BDNF); apolipoprotein E (APOE); angiotensin I-converting enzyme (ACE) and vascular endothelial growth factor (VEGF) genes in mediating response to ECT are summarized. The existing data support the notion that some genetic factors-particularly the functional COMT val158met polymorphism-may play a role in the magnitude of clinical response to ECT, and thus could serve as potential biomarkers for future personalized treatment approaches. However, much of the work to date is preliminary, and large-scale confirmatory studies are still needed. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Janine J Benson-Martin
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
| | - Dan J Stein
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
| | - David S Baldwin
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.,Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Katharina Domschke
- Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
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31
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Sartorius A, Demirakca T, Böhringer A, Clemm von Hohenberg C, Aksay SS, Bumb JM, Kranaster L, Ende G. Electroconvulsive therapy increases temporal gray matter volume and cortical thickness. Eur Neuropsychopharmacol 2016; 26:506-17. [PMID: 26792445 DOI: 10.1016/j.euroneuro.2015.12.036] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 10/14/2015] [Accepted: 12/20/2015] [Indexed: 02/06/2023]
Abstract
Electroconvulsive therapy (ECT) is a treatment of choice for severe and therapy resistant forms of major depressive episodes (MDE). Temporal brain volume alterations in MDE have been described for more than two decades. In our prospective study we aimed to investigate individual pre-post ECT treatment whole brain gray matter (GM) volume changes (quantified with voxel-based morphometry) in a sample of 18 patients with MDE. In addition, we studied the effect of ECT on voxel-based cortical thickness in cortical brain regions. The most prominent longitudinal GM increases (significant at a whole brain corrected level) occurred in temporal lobe regions. Within specific region of interest analyses we detected highly significant increases of GM in the hippocampus and the amygdala and to a lesser extent in the habenula (left p=0.003, right p=0.032). A voxel based cortical thickness analysis revealed an increase in cortical temporal regions (basically temporal pole and insula) further corroborating our cortical voxel-based morphometry results. Neither GM decreases or white matter increases nor correlations of GM changes with basic psychopathological parameters were detected. We corroborate earlier findings of hippocampal and amygdala GM volume increase following an acute ECT series in patients with MDE. Temporal GM volume increase was significant on a whole brain level and further corroborated by a cortical thickness analysis. Our data widely exclude white matter loss as an indirect cause of GM growth. Our data add further evidence to the hypothesis that ECT enables plasticity falsifying older ideas of ECT induced "brain damaging".
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Affiliation(s)
- Alexander Sartorius
- Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
| | - Traute Demirakca
- Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | - Andreas Böhringer
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | - Christian Clemm von Hohenberg
- Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | - Suna Su Aksay
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | - Jan Malte Bumb
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | - Laura Kranaster
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | - Gabriele Ende
- Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
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32
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Trevithick L, McAllister-Williams RH, Blamire A, Branton T, Clark R, Downey D, Dunn G, Easton A, Elliott R, Ellwell C, Hayden K, Holland F, Karim S, Lowe J, Loo C, Nair R, Oakley T, Prakash A, Sharma PK, Williams SR, Anderson IM. Study protocol for the randomised controlled trial: Ketamine augmentation of ECT to improve outcomes in depression (Ketamine-ECT study). BMC Psychiatry 2015; 15:257. [PMID: 26489663 PMCID: PMC4618126 DOI: 10.1186/s12888-015-0641-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 10/08/2015] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND There is a robust empirical evidence base supporting the acute efficacy of electroconvulsive therapy (ECT) for severe and treatment resistant depression. However, a major limitation, probably contributing to its declining use, is that ECT is associated with impairment in cognition, notably in anterograde and retrograde memory and executive function. Preclinical and preliminary human data suggests that ketamine, used either as the sole anaesthetic agent or in addition to other anaesthetics, may reduce or prevent cognitive impairment following ECT. A putative hypothesis is that ketamine, through antagonising glutamate receptors, protects from excess excitatory neurotransmitter stimulation during ECT. The primary aim of the ketamine-ECT study is to investigate whether adjunctive ketamine can attenuate the cognitive impairment caused by ECT. Its secondary aim is to examine if ketamine increases the speed of clinical improvement with ECT. METHODS/DESIGN The ketamine ECT study is a multi-site randomised, placebo-controlled, double blind trial. It was originally planned to recruit 160 moderately to severely depressed patients who had been clinically prescribed ECT. This recruitment target was subsequently revised to 100 patients due to recruitment difficulties. Patients will be randomly allocated on a 1:1 basis to receive either adjunctive ketamine or saline in addition to standard anaesthesia for ECT. The primary neuropsychological outcome measure is anterograde verbal memory (Hopkins Verbal Learning Test-Revised delayed recall task) after 4 ECT treatments. Secondary cognitive outcomes include verbal fluency, autobiographical memory, visuospatial memory and digit span. Efficacy is assessed using observer and self-report efficacy measures of depressive symptomatology. The effects of ECT and ketamine on cortical activity during cognitive tasks will be studied in a sub-sample using functional near-infrared spectroscopy (fNIRS). DISCUSSION The ketamine-ECT study aims to establish whether or not adjunctive ketamine used together with standard anaesthesia for ECT will significantly reduce the adverse cognitive effects observed after ECT. Potential efficacy benefits of increased speed of symptom improvement and a reduction in the number of ECT treatments required will also be assessed, as will safety and tolerability of adjunctive ketamine. This study will provide important evidence as to whether adjunctive ketamine is routinely indicated for ECT given for depression in routine NHS clinical practice. TRIAL REGISTRATION Current Controlled Trials: ISRCTN14689382 (assigned 30/07/2012); EudraCT Number: 2011-005476-41.
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Affiliation(s)
- Liam Trevithick
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
- Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK.
| | - R Hamish McAllister-Williams
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
- Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK.
| | - Andrew Blamire
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
| | - Tim Branton
- Leeds and York Partnership NHS Foundation Trust, Leeds, UK.
| | - Ross Clark
- Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
| | - Darragh Downey
- Neuroscience and Psychiatry Unit, The University of Manchester and Manchester Academic Health Science Centre, Room G809, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
| | - Graham Dunn
- Biostatistics Group, The University of Manchester, Manchester, UK.
| | | | - Rebecca Elliott
- Neuroscience and Psychiatry Unit, The University of Manchester and Manchester Academic Health Science Centre, Room G809, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
| | - Clare Ellwell
- Biomedical Optics Research Laboratory, University College London, London, UK.
| | | | - Fiona Holland
- Biostatistics Group, The University of Manchester, Manchester, UK.
| | - Salman Karim
- Lancashire Care NHS Foundation Trust/ The University of Manchester, Preston, UK.
| | - Jo Lowe
- Neuroscience and Psychiatry Unit, The University of Manchester and Manchester Academic Health Science Centre, Room G809, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
| | - Colleen Loo
- School of Psychiatry, University of New South Wales, Sydney, Australia.
| | - Rajesh Nair
- Tees, Esk and Wear Valley NTW NHS Foundation Trust, Darlington, UK.
| | - Timothy Oakley
- Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK.
| | | | | | - Stephen R Williams
- Imaging Science and Biomedical Imaging Institute, The University of Manchester, Manchester, UK.
| | - Ian M Anderson
- Neuroscience and Psychiatry Unit, The University of Manchester and Manchester Academic Health Science Centre, Room G809, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
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33
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Yuan H, Young KD, Phillips R, Zotev V, Misaki M, Bodurka J. Resting-state functional connectivity modulation and sustained changes after real-time functional magnetic resonance imaging neurofeedback training in depression. Brain Connect 2015; 4:690-701. [PMID: 25329241 DOI: 10.1089/brain.2014.0262] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in rehabilitating emotion regulation in depression.
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Affiliation(s)
- Han Yuan
- 1 Laureate Institute for Brain Research , Tulsa, Oklahoma
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Magnetic Seizure Therapy for Unipolar and Bipolar Depression: A Systematic Review. Neural Plast 2015; 2015:521398. [PMID: 26075100 PMCID: PMC4444586 DOI: 10.1155/2015/521398] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Accepted: 12/15/2014] [Indexed: 01/14/2023] Open
Abstract
UNLABELLED Objective. Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. MST might prove to be a valuable tool in the treatment of mood disorders, such as major depressive disorder (MDD) and bipolar disorder. Our aim is to review current literature on MST. Methods. OVID and MEDLINE databases were used to systematically search for clinical studies on MST. The terms "magnetic seizure therapy," "depression," and "bipolar" were employed. Results. Out of 74 studies, 8 met eligibility criteria. There was considerable variability in the methods employed and samples sizes were small, limiting the generalization of the results. All studies focused on depressive episodes, but few included patients with bipolar disorder. The studies found reported significant antidepressant effects, with remission rates ranging from 30% to 40%. No significant cognitive side effects related to MST were found, with a better cognitive profile when compared to ECT. CONCLUSION MST was effective in reducing depressive symptoms in mood disorders, with generally less side effects than ECT. No study focused on comparing MST to ECT on bipolar depression specifically.
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Bumb JM, Aksay SS, Janke C, Kranaster L, Geisel O, Gass P, Hellweg R, Sartorius A. Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients. Eur Arch Psychiatry Clin Neurosci 2015; 265:227-32. [PMID: 25231834 DOI: 10.1007/s00406-014-0543-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 09/10/2014] [Indexed: 12/11/2022]
Abstract
Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.
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Affiliation(s)
- Jan Malte Bumb
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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Burgese DF, Bassitt DP. Variation of plasma cortisol levels in patients with depression after treatment with bilateral electroconvulsive therapy. TRENDS IN PSYCHIATRY AND PSYCHOTHERAPY 2015; 37:27-36. [DOI: 10.1590/2237-6089-2014-0031] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 11/19/2014] [Indexed: 11/21/2022]
Abstract
Introduction: More than 60 years after the introduction of modern psychopharmacology, electroconvulsive therapy (ECT) continues to be an essential therapeutic modality in the treatment of mental disorders, but its mechanism of action remains unclear. Hormones play an essential role in the development and expression of a series of behavioral changes. One aspect of the influence of hormones on behavior is their potential contribution to the pathophysiology of psychiatric disorders and the mechanism of action of psychotropic drugs and ECT.Objective: We measured blood levels of the hormone cortisol in patients with unipolar depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and compared results with levels found in healthy adults.Method: Blood cortisol levels were measured before the beginning of treatment with ECT, at the seventh session, and at the last session, at treatment completion. Depression symptoms were assessed using the Beck Depression Inventory (BDI).Results: Cortisol levels remained stable in both men and women between the seventh and the last sessions of ECT; values ranged from 0.686±9.6330 g/dL for women, and there was a mean decrease of 5.825±6.0780 g/dL (p = 0.024). Mean number of ECT sessions was 12. After the seventh and the last ECT sessions, patients with depression and individuals in the control group had similar cortisol levels, whereas BDI scores remained different.Conclusion: Cortisol levels decreased during ECT treatment. ECT seems to act as a regulator of the hypothalamic-pituitaryadrenal axis.
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Wei Q, Tian Y, Yu Y, Zhang F, Hu X, Dong Y, Chen Y, Hu P, Hu X, Wang K. Modulation of interhemispheric functional coordination in electroconvulsive therapy for depression. Transl Psychiatry 2014; 4:e453. [PMID: 25268257 PMCID: PMC4202999 DOI: 10.1038/tp.2014.101] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 08/19/2014] [Accepted: 08/22/2014] [Indexed: 12/15/2022] Open
Abstract
Considerable evidence suggests that depression is related to interhemispheric functional coordination deficits. For depression, electroconvulsive therapy (ECT) is the most rapid and effective therapy, but its underlying mechanism remains unknown. The aim of this study was to explore the impact of ECT on the interhemispheric functional coordination in depression patients. We used resting-state functional magnetic resonance imaging to observe the change of interhemispheric functional coordination with the method of voxel-mirrored homotopic connectivity (VMHC) in 11 depressed patients before and after ECT, compared with 15 healthy controls. The results showed that, compared with depression patients before ECT, VMHC was significantly increased in superior frontal gyri (BA 8), middle frontal gyri (two clusters: BA 8/9 and BA 10) and angular gyri (BA 39) in depression patients after ECT. Compared with healthy controls, VMHC in those areas was significantly lower in the middle frontal gyri (BA 8/9) and angular gyri (BA 39) in depression patients before ECT, but no significant difference was observed in the superior frontal gyri (BA 8) and middle frontal gyri (BA 10). There was no significant correlation between the changes of Hamilton Depression Rating Scale scores and changed VMHC values in those four areas in depression patients. The results suggest that ECT selectively modulated interhemispheric functional coordination in depression patients. Such may play an important mechanistic role in the treatment of depression, and may afford a useful avenue for optimizing treatment.
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Affiliation(s)
- Q Wei
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Y Tian
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Y Yu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - F Zhang
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - X Hu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Y Dong
- Anhui Mental Health Center, Hefei, China
| | - Y Chen
- Anhui Mental Health Center, Hefei, China
| | - P Hu
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - X Hu
- Anhui Mental Health Center, Hefei, China
| | - K Wang
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. Int J Neuropsychopharmacol 2014; 17:1487-500. [PMID: 24606669 DOI: 10.1017/s1461145714000248] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The enzymatic activity of histone deacetylases (HDACs) leads to a histone deacetylation-mediated condensed chromatic structure, resulting in transcriptional repression, which has been implicated in the modifications of neural circuits and behaviors. Repeated treatment with electroconvulsive seizure (ECS) induces changes in histone acetylation, expression of various genes, and intrabrain cellular changes, including neurogenesis. In this study, we examined the effects of repeated ECS on the expression of class I HDACs and related changes in histone modifications and gene expression in the rat frontal cortex. Ten days of repeated ECS treatments (E10X) up-regulated HDAC2 expression at the mRNA and protein levels in the rat frontal cortex compared with sham-treated controls; this was evident in the nuclei of neuronal cells in the prefrontal, cingulate, orbital, and insular cortices. Among the known HDAC2 target genes, mRNA expression of N-methyl-d-aspartate (NMDA) receptor signaling-related genes, including early growth response-1 (Egr1), c-Fos, glutamate receptor, ionotropic, N-methyl d-aspartate 2A (Nr2a), Nr2b, neuritin1 (Nrn1), and calcium/calmodulin-dependent protein kinase II alpha (Camk2α), were decreased, and the histone acetylation of H3 and/or H4 proteins was also reduced by E10X. Chromatin immunoprecipitation analysis revealed that HDAC2 occupancy in the promoters of down-regulated genes was increased significantly. Moreover, administration of sodium butyrate, a HDAC inhibitor, during the course of E10X ameliorated the ECS-induced down-regulation of genes in the rat frontal cortex. These findings suggest that induction of HDAC2 by repeated ECS treatment could play an important role in the down-regulation of NMDA receptor signaling-related genes in the rat frontal cortex through histone modification.
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Rohan ML, Yamamoto RT, Ravichandran CT, Cayetano KR, Morales OG, Olson DP, Vitaliano G, Paul SM, Cohen BM. Rapid mood-elevating effects of low field magnetic stimulation in depression. Biol Psychiatry 2014; 76:186-93. [PMID: 24331545 DOI: 10.1016/j.biopsych.2013.10.024] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Revised: 09/18/2013] [Accepted: 10/12/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND We previously reported rapid mood elevation following an experimental magnetic resonance imaging procedure in depressed patients with bipolar disorder (BPD). This prompted the design, construction, and testing of a portable electromagnetic device that reproduces only the rapidly oscillating (1 kHz, <1 V/m) electromagnetic field of the experimental procedure, called low field magnetic stimulation (LFMS). METHODS We used a randomized, double blind, sham controlled treatment protocol to study the effects of LFMS in a large group of stably medicated, depressed patients with either BPD (n = 41) or major depressive disorder (n = 22). Subjects received a single, 20-minute treatment. Change in mood was assessed immediately afterward using a visual analog scale (VAS), the 17-item Hamilton Depression Rating Scale (HDRS-17), and the Positive and Negative Affect Schedule scales. RESULTS Substantial improvement (>10% of baseline) in mood was observed following LFMS treatment relative to sham treatment for both diagnostic subgroups for our primary outcomes, the VAS and the HDRS-17. These differences were not statistically significant in primary analyses stratifying by diagnosis but were significant in secondary analyses combining data across the two diagnostic groups (p = .01 VAS, p = .02 HDRS-17). Rapid improvement in mood was also observed using the Positive and Negative Affect Schedule scales as secondary measures (positive affect scale p = .02 BPD, p = .002 combined group). A finite element method calculation indicates a broad penetration of the LFMS electric field throughout the cerebral cortex. CONCLUSIONS Low field magnetic stimulation may produce rapid changes in mood using a previously unexplored range of electromagnetic fields.
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Affiliation(s)
- Michael L Rohan
- McLean Hospital and the Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts.
| | - Rinah T Yamamoto
- McLean Hospital and the Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts
| | - Caitlin T Ravichandran
- Departments of Neuroscience (Mind and Brain Institute), Psychiatry, and Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York
| | - Kenroy R Cayetano
- McLean Hospital and the Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts
| | - Oscar G Morales
- Departments of Neuroscience (Mind and Brain Institute), Psychiatry, and Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York
| | - David P Olson
- McLean Hospital and the Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts
| | - Gordana Vitaliano
- Departments of Neuroscience (Mind and Brain Institute), Psychiatry, and Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York
| | - Steven M Paul
- Departments of Neuroscience (Mind and Brain Institute), Psychiatry, and Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York
| | - Bruce M Cohen
- Departments of Neuroscience (Mind and Brain Institute), Psychiatry, and Pharmacology, Weill Cornell Medical College of Cornell University, New York, New York
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Levinstein MR, Samuels BA. Mechanisms underlying the antidepressant response and treatment resistance. Front Behav Neurosci 2014; 8:208. [PMID: 25018708 PMCID: PMC4073308 DOI: 10.3389/fnbeh.2014.00208] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 05/22/2014] [Indexed: 12/28/2022] Open
Abstract
Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.
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Affiliation(s)
- Marjorie R Levinstein
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, Research Foundation for Mental Hygiene, Inc. New York, NY, USA
| | - Benjamin A Samuels
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, Research Foundation for Mental Hygiene, Inc. New York, NY, USA
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Abstract
OBJECTIVES The Mental Health Act (MHA) 2001 provides the legislative structure in Ireland for the involuntary admission and treatment, including with ECT, of patients suffering from mental disorders. A recent Seanad Bill proposed removing the option of administering ECT to involuntary patients who do not provide informed consent. This controversial issue has stimulated extensive media and stakeholder debate. In this study we explored the attitudes of consultant psychiatrists towards prescribing ECT for involuntary patients. METHODS We compiled a current list of consultant psychiatrists attached to approved centres nationwide. We sent a study specific questionnaire to consultants of all adult psychiatry specialties. RESULTS From the 249 individualised anonymous questionnaires posted, 164 (66%) were returned and analysed. When clinically indicated for involuntary patients willing to consent to ECT treatment, 159 (97%) consultants stated that they would and three (2%) would not prescribe ECT. For involuntary patients who lack capacity and are unable to consent, 157 (96%) consultant psychiatrists stated that they would and six (4%) that they would not prescribe ECT. For involuntary patients who have capacity to consent but are unwilling to do so, 52 (32%) consultant psychiatrists stated they would and 104 (63%) would not prescribe ECT. CONCLUSIONS The overwhelming majority of consultant psychiatrists would prescribe ECT for involuntary patients who are unable to consent to this treatment. Divergent attitudes emerged for treating patients who are unwilling to consent, with most consultant psychiatrists stating they would not prescribe ECT for this patient group.
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Peng L, Min S, Wei K, Ziemann‐Gimmel P. Different regimens of intravenous sedatives or hypnotics for electroconvulsive therapy (ECT) in adult patients with depression. Cochrane Database Syst Rev 2014; 2014:CD009763. [PMID: 24723301 PMCID: PMC6464335 DOI: 10.1002/14651858.cd009763.pub2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Depression is a common mental disorder. It affects millions of people worldwide and is considered by the World Health Organization (WHO) to be one of the leading causes of disability. Electroconvulsive therapy (ECT) is a well-established treatment for severe depression. Intravenous anaesthetic medication is used to minimize subjective unpleasantness and adverse side effects of the induced tonic-clonic seizure. The influence of different anaesthetic medications on the successful reduction of depressive symptoms and adverse effects is unclear. OBJECTIVES This review evaluated the effects of different regimens of intravenous sedatives and hypnotics on anti-depression efficacy, recovery and seizure duration in depressed adults undergoing ECT. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from 1966 to 31 December 2012). We handsearched related journals and applied no language restrictions. SELECTION CRITERIA We included randomized controlled trials (RCTs) and cross-over trials evaluating the effects of different intravenous sedatives and hypnotics for ECT. We excluded studies and trials using placebo or inhalational anaesthetics and studies that used no anaesthetic. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. When possible, data were pooled and risk ratios (RRs) and mean differences (MDs), each with 95% confidence intervals (CIs), were computed using the Cochrane Review Manager statistical package (RevMan). MAIN RESULTS We included in the review 18 RCTs (599 participants; published between 1994 and 2012). Most of the included trials were at high risk of bias.We analysed the results of studies comparing six different intravenous anaesthetics.Only a few studies comparing propofol with methohexital (four studies) and with thiopental (three studies) could be pooled.No difference was noted in the reduction of depression scores observed in participants treated with propofol compared with methohexital (low-quality evidence). These four studies were not designed to detect differences in depression scores.The duration of electroencephalograph (EEG) and of motor seizures was shorter in the propofol group compared with the methohexital group (low-quality evidence). No difference was seen in EEG seizure duration when propofol was compared with thiopental (low-quality evidence).Time to recovery (following commands) was longer among participants after anaesthesia with thiopental compared with propofol (low-quality evidence).For the remaining comparisons of anaesthetics, only single studies or insufficient data were available. Adverse events were inadequately reported in eligible trials, and none of the included trials reported anaesthesia-related mortality. AUTHORS' CONCLUSIONS Most of the included studies were at high risk of bias, and the quality of evidence was generally low. The studies were not designed to detect clinically relevant differences in depression scores. Anaesthetic agents should be chosen on the basis of adverse effect profile, emergence and how these medications affect seizure duration. If it is difficult to elicit an adequately long seizure, methohexital may be superior to propofol (low-quality evidence). If a patient is slow to recover from anaesthesia, propofol may allow a faster time to follow commands than thiopental (low-quality evidence). A factor of clinical concern that was not addressed by any study was adrenal suppression from etomidate. Optimal dosages of intravenous sedatives or hypnotics have not yet been determined.Larger well-designed randomized studies are needed to determine which intravenous anaesthetic medication leads to the greatest improvement in depression scores with minimal adverse effects.
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Affiliation(s)
- Lihua Peng
- The First Affiliated Hospital, Chongqing Medical UniversityThe Department of Anaesthesia and Pain MedicineNo 1 Youyi Road, Yuan‐jia‐gangYu‐zhong DistrictChongqingChina40016
| | - Su Min
- The First Affiliated Hospital, Chongqing Medical UniversityThe Department of Anaesthesia and Pain MedicineNo 1 Youyi Road, Yuan‐jia‐gangYu‐zhong DistrictChongqingChina40016
| | - Ke Wei
- The First Affiliated Hospital, Chongqing Medical UniversityDepartment of Anaesthesia and Pain Medicine1# Youyi Road, Yuanjiangang CommunityYuzhong DistrictChongqingChina400016
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Young KD, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder. PLoS One 2014; 9:e88785. [PMID: 24523939 PMCID: PMC3921228 DOI: 10.1371/journal.pone.0088785] [Citation(s) in RCA: 168] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 01/12/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD), and normalize with remission. Real-time functional MRI neurofeedback (rtfMRI-nf) offers a non-invasive method to modulate this regional activity. We examined whether depressed participants can use rtfMRI-nf to enhance amygdala responses to positive autobiographical memories, and whether this ability alters symptom severity. METHODS Unmedicated MDD subjects were assigned to receive rtfMRI-nf from either left amygdala (LA; experimental group, n = 14) or the horizontal segment of the intraparietal sulcus (HIPS; control group, n = 7) and instructed to contemplate happy autobiographical memories (AMs) to raise the level of a bar representing the hemodynamic signal from the target region to a target level. This 40s Happy condition alternated with 40s blocks of rest and counting backwards. A final Transfer run without neurofeedback information was included. RESULTS Participants in the experimental group upregulated their amygdala responses during positive AM recall. Significant pre-post scan decreases in anxiety ratings and increases in happiness ratings were evident in the experimental versus control group. A whole brain analysis showed that during the transfer run, participants in the experimental group had increased activity compared to the control group in left superior temporal gyrus and temporal polar cortex, and right thalamus. CONCLUSIONS Using rtfMRI-nf from the left amygdala during recall of positive AMs, depressed subjects were able to self-regulate their amygdala response, resulting in improved mood. Results from this proof-of-concept study suggest that rtfMRI-nf training with positive AM recall holds potential as a novel therapeutic approach in the treatment of depression.
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Affiliation(s)
- Kymberly D. Young
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
| | - Vadim Zotev
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
| | - Raquel Phillips
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
| | - Masaya Misaki
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
| | - Han Yuan
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
| | - Wayne C. Drevets
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
- Janssen Pharmaceuticals, LCC, of Johnson & Johnson, Inc., Titusville, New Jersey, United States of America
| | - Jerzy Bodurka
- Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America
- Center for Biomedical Engineering, The University of Oklahoma, Norman, Oklahoma, United States of America
- College of Engineering, The University of Oklahoma, Norman, Oklahoma, United States of America
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Nordgren M, Karlsson T, Svensson M, Koczy J, Josephson A, Olson L, Tingström A, Brené S. Orchestrated regulation of Nogo receptors, LOTUS, AMPA receptors and BDNF in an ECT model suggests opening and closure of a window of synaptic plasticity. PLoS One 2013; 8:e78778. [PMID: 24244357 PMCID: PMC3828303 DOI: 10.1371/journal.pone.0078778] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 09/18/2013] [Indexed: 01/16/2023] Open
Abstract
Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements.
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Affiliation(s)
- Max Nordgren
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Tobias Karlsson
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Maria Svensson
- Psychiatric Neuromodulation Unit, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden
| | - Josefin Koczy
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Anna Josephson
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Lars Olson
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Anders Tingström
- Psychiatric Neuromodulation Unit, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden
| | - Stefan Brené
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- * E-mail:
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Merkl A, Schneider GH, Schönecker T, Aust S, Kühl KP, Kupsch A, Kühn AA, Bajbouj M. Antidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression. Exp Neurol 2013; 249:160-8. [DOI: 10.1016/j.expneurol.2013.08.017] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2013] [Revised: 08/22/2013] [Accepted: 08/27/2013] [Indexed: 01/19/2023]
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Dopamine D₃ receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression. Int J Neuropsychopharmacol 2013; 16:1443-59. [PMID: 22093107 DOI: 10.1017/s1461145711001659] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Dysfunction of dopamine D₃ receptors, particularly in the mesocorticolimbic system, has been linked to the pathogenesis of major depression. Preclinical data show enhanced D₃ receptor binding in the striatum upon antidepressant medication and electroconvulsive therapy (ECT). Thus, the potential impact of dopamine D₃ receptor gene (DRD3) variation on ECT outcome in treatment-resistant major depression was evaluated by applying a combined molecular and imaging genetic approach. Altogether, 10 representative variants covering 95.4% of DRD3 gene variation were investigated for association with response to ECT in a sample of 104 (71 female, 33 male) Caucasian patients with pharmacorefractory major depression. Additionally, ventral striatum responsiveness to happy faces was assessed in two independent samples of depressed patients (total N=54) by means of functional magnetic resonance imaging at 3 T. Significant association of DRD3 rs3732790, rs3773679 and rs9817063 variants with response (uncorrected p=0.02-0.03) and remission (uncorrected p=0.01) after ECT was discerned. Logistic regression analyses revealed association of rs3732790 (uncorrected p=0.009; corrected p=0.045) and rs3773679 (uncorrected p=0.009; corrected p=0.045) with remission when applying a recessive model of inheritance. The rs3732790T allele conferring a more favourable treatment response was furthermore found to be associated with stronger striatal responsiveness to happy facial expressions (sample 1: cluster-corrected p=0.002; sample 2: p=0.023). In summary, the present study suggests some impact of DRD3 gene variation on ECT response, potentially mediated by alteration of striatal engagement during the processing of emotionally rewarding stimuli.
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The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 2012; 37:2331-71. [PMID: 23261405 DOI: 10.1016/j.neubiorev.2012.12.007] [Citation(s) in RCA: 342] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Revised: 11/26/2012] [Accepted: 12/10/2012] [Indexed: 12/18/2022]
Abstract
We present a comprehensive overview of the neurobiology of unipolar major depression and antidepressant drug action, integrating data from affective neuroscience, neuro- and psychopharmacology, neuroendocrinology, neuroanatomy, and molecular biology. We suggest that the problem of depression comprises three sub-problems: first episodes in people with low vulnerability ('simple' depressions), which are strongly stress-dependent; an increase in vulnerability and autonomy from stress that develops over episodes of depression (kindling); and factors that confer vulnerability to a first episode (a depressive diathesis). We describe key processes in the onset of a 'simple' depression and show that kindling and depressive diatheses reproduce many of the neurobiological features of depression. We also review the neurobiological mechanisms of antidepressant drug action, and show that resistance to antidepressant treatment is associated with genetic and other factors that are largely similar to those implicated in vulnerability to depression. We discuss the implications of these conclusions for the understanding and treatment of depression, and make some strategic recommendations for future research.
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Peterchev AV, Wagner TA, Miranda PC, Nitsche MA, Paulus W, Lisanby SH, Pascual-Leone A, Bikson M. Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices. Brain Stimul 2012; 5:435-53. [PMID: 22305345 PMCID: PMC3346863 DOI: 10.1016/j.brs.2011.10.001] [Citation(s) in RCA: 255] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Accepted: 10/05/2011] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. METHODS This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. RESULTS The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. CONCLUSIONS We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated.
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Affiliation(s)
- Angel V Peterchev
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina 27710, USA.
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Linden DEJ, Habes I, Johnston SJ, Linden S, Tatineni R, Subramanian L, Sorger B, Healy D, Goebel R. Real-time self-regulation of emotion networks in patients with depression. PLoS One 2012; 7:e38115. [PMID: 22675513 PMCID: PMC3366978 DOI: 10.1371/journal.pone.0038115] [Citation(s) in RCA: 251] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Accepted: 04/30/2012] [Indexed: 12/28/2022] Open
Abstract
Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression.
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Affiliation(s)
- David E J Linden
- Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, United Kingdom.
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Plakiotis C, George K, O'Connor DW. Has electroconvulsive therapy use remained stable over time? A decade of electroconvulsive therapy service provision in Victoria, Australia. Aust N Z J Psychiatry 2012; 46:522-31. [PMID: 22375067 DOI: 10.1177/0004867412440190] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Despite the long history of electroconvulsive therapy (ECT) as a psychiatric treatment modality in Australia, existing literature regarding ECT use and practices in Australia is limited. In this unique study, we report ECT provision in Victoria to adults aged 25 years and over from 1998 to 2007, based on complete data from all public and private treatment settings within the State; compare our results to previous literature in the field; and offer possible explanations for these findings as a basis for future research. METHOD Analysis of statutory ECT service provision data collected by the Office of the Chief Psychiatrist of Victoria. RESULTS ECT use declined overall from 2001 onward, followed by a small increase in use in 2007. Eighty per cent of patients received ECT for depression and 14% for psychosis. Sixty-two per cent of ECT recipients were women. Although patients aged 65 years and over were small in number, age adjustment of data was indicative of a higher utilisation rate in this group. With increasing age, the percentage of ECT recipients treated for depression increased, whereas the percentage treated for psychosis decreased. Sixty per cent of patients were treated in the public sector. Public-private sector ECT use did not differ greatly for depression, but more patients were treated in the public sector for psychosis. The majority of patients with depression received treatment voluntarily, but the converse was true for patients with psychosis. Unilateral electrode placement predominated. CONCLUSIONS While utilisation rates gradually declined over the decade studied, patients continued receiving ECT in significant numbers, suggesting its role in treating severe mental illness is far from superceded. The present, population-level research cannot explain the causative factors underlying the patterns observed, but raises interesting questions for further investigation. Ongoing collection of statutory ECT data in a manner making it amenable to research applications is recommended.
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Affiliation(s)
- Chris Plakiotis
- School of Psychology and Psychiatry, Monash University, Victoria, Australia.
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