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Lolansen C, Howard CJ, Mitra S, Badham SP. The role of individual differences and attitude in willingness to participate in TMS studies. Behav Res Methods 2025; 57:110. [PMID: 40063211 PMCID: PMC11893711 DOI: 10.3758/s13428-025-02623-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/14/2025]
Abstract
Finding neurophysiological research participants can be challenging, especially when the technology used in the research study is less known, such as transcranial magnetic stimulation (TMS). Despite this well-known phenomenon, there is limited literature investigating the factors involved in willingness to participate and perceived barriers from the potential participants' perspective. This paper explored the relationship between individual differences, attitudes toward TMS, and willingness to participate in TMS research alongside perceived barriers to participation and concerns when considering participating. The findings suggest that participants who had more positive attitudes towards TMS were more willing to participate. Participants frequently reported being concerned about safety, including risks and side effects. For barriers in terms of safety parameters, the number of participants who were eligible based on their TMS safety screening questionnaire was low, particularly for older adults. These findings are discussed in the context of the literature, and practical guidelines are provided for researchers looking to plan TMS recruitment.
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Affiliation(s)
- C Lolansen
- School of Psychology, University of Nottingham, University Park Campus, East Dr, Nottingham, NG7 2RD, UK.
| | - C J Howard
- Department of Psychology, Nottingham Trent University, Nottingham, NG1 4BU, UK
| | - S Mitra
- Department of Psychology, Nottingham Trent University, Nottingham, NG1 4BU, UK
| | - S P Badham
- Department of Psychology, Nottingham Trent University, Nottingham, NG1 4BU, UK
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Trapp NT, Purgianto A, Taylor JJ, Singh MK, Oberman LM, Mickey BJ, Youssef NA, Solzbacher D, Zebley B, Cabrera LY, Conroy S, Cristancho M, Richards JR, Flood MJ, Barbour T, Blumberger DM, Taylor SF, Feifel D, Reti IM, McClintock SM, Lisanby SH, Husain MM. Consensus review and considerations on TMS to treat depression: A comprehensive update endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol 2025; 170:206-233. [PMID: 39756350 PMCID: PMC11825283 DOI: 10.1016/j.clinph.2024.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 11/13/2024] [Accepted: 12/01/2024] [Indexed: 01/07/2025]
Abstract
This article updates the prior 2018 consensus statement by the National Network of Depression Centers (NNDC) on the use of transcranial magnetic stimulation (TMS) in the treatment of depression, incorporating recent research and clinical developments. Publications on TMS and depression between September 2016 and April 2024 were identified using methods informed by PRISMA guidelines. The NNDC Neuromodulation Work Group met monthly between October 2022 and April 2024 to define important clinical topics and review pertinent literature. A modified Delphi method was used to achieve consensus. 2,396 abstracts and manuscripts met inclusion criteria for review. The work group generated consensus statements which include an updated narrative review of TMS safety, efficacy, and clinical features of use for depression. Considerations related to training, roles/responsibilities of providers, and documentation are also discussed. TMS continues to demonstrate broad evidence for safety and efficacy in treating depression. Newer forms of TMS are faster and potentially more effective than conventional repetitive TMS. Further exploration of targeting methods, use in special populations, and accelerated protocols is encouraged. This article provides an updated overview of topics relevant to the administration of TMS for depression and summarizes expert, consensus opinion on the practice of TMS in the United States.
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Affiliation(s)
- Nicholas T Trapp
- Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
| | - Anthony Purgianto
- Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Joseph J Taylor
- Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Manpreet K Singh
- Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA, USA
| | - Lindsay M Oberman
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA
| | - Brian J Mickey
- Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, USA
| | - Nagy A Youssef
- Pine Rest Christian Mental Health Services, Grand Rapids, MI, USA; Division of Psychiatry and Behavioral Medicine, Michigan State University, Grand Rapids, MI, USA
| | - Daniela Solzbacher
- Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, USA
| | - Benjamin Zebley
- Department of Psychiatry, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY, USA
| | - Laura Y Cabrera
- Department of Engineering Science and Mechanics, Center for Neural Engineering, Pennsylvania State University, University Park, PA, USA
| | - Susan Conroy
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mario Cristancho
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
| | - Jackson R Richards
- Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | | | - Tracy Barbour
- Division of Neuropsychiatry and Neuromodulation, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniel M Blumberger
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
| | - Stephan F Taylor
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
| | - David Feifel
- Kadima Neuropsychiatry Institute, La Jolla, CA, USA; University of California-San Diego, San Diego, CA, USA
| | - Irving M Reti
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Shawn M McClintock
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas,TX, USA
| | - Sarah H Lisanby
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA; Division of Translational Research, National Institute of Mental Health, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
| | - Mustafa M Husain
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas,TX, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
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Chang CH, Liu WC, Chou PH. Near-infrared spectroscopy-guided personalized repetitive transcranial magnetic stimulation for bipolar depression: a case report. Front Psychiatry 2025; 15:1514153. [PMID: 39902251 PMCID: PMC11788398 DOI: 10.3389/fpsyt.2024.1514153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 12/27/2024] [Indexed: 02/05/2025] Open
Abstract
Introduction Transcranial magnetic stimulation (TMS) is a common treatment for depression, particularly in patients unresponsive to conventional therapies. High-frequency (10 Hz), low-frequency (1 Hz), or bilateral (left, high-frequency; right, low-frequency) stimulation of the dorsolateral prefrontal cortex (DLPFC) has been demonstrated to be effective in studies based on prefrontal asymmetry theory, which suggests that depression is associated with reduced left frontal function and increased right frontal function. However, few reliable predictors or biomarkers are available for personalizing treatment protocols on the basis of a patient's brain function. Near-infrared spectroscopy (NIRS), a noninvasive neuroimaging tool that assesses functional changes in the brain during cognitive tasks, can measure a patient's bilateral frontal lobe function in real time. Thus, this tool can aid the development of personalized TMS protocols for patients with depression. Methods A 19-year-old woman presented to our psychiatric clinic with bipolar depression. NIRS was performed to select an appropriate TMS protocol for the patient. A verbal fluency test revealed bilateral low frontal lobe function. Thus, we selected a TMS protocol involving 10 sessions of bilateral high-frequency stimulation over 4 days, with each session delivering 3000 pulses on each side of the DLPFC. Results Before treatment, the patient's scores on the Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Young Mania Rating Scale were 40, 57, 40, and 6, respectively. After treatment, her depressive symptoms substantially improved, with HAMD, BDI, and BAI scores decreasing to 17, 21, and 14, respectively. Although the treatment led to side effects such as dizziness and headache, these effects resolved after the treatment. At the 6-month follow-up, the patient's condition was still stable, with HAMD, BDI, and BAI scores of 10, 13, and 7, respectively. Conclusion Our case suggests that NIRS can guide the selection of appropriate TMS protocols for patients with bipolar depression. Although our findings are promising, further randomized controlled trials are needed to validate the efficacy and safety of and determine the optimal parameters for this approach.
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Affiliation(s)
- Chun-Hung Chang
- An Nan Hospital, China Medical University, Tainan, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
| | - Wen-Chun Liu
- Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan
| | - Po-Han Chou
- Department of Brain Reserch, Brain Mental Health Clinic, Zubei, Taiwan
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Manocchio F, Enepekides J, Nestor S, Giacobbe P, Rabin JS, Burke MJ, Lanctôt KL, Goubran M, Meng Y, Lipsman N, Hamani C, Davidson B. Neuromodulation as a therapeutic approach for post-traumatic stress disorder: the evidence to date. Expert Rev Neurother 2025; 25:101-120. [PMID: 39704493 DOI: 10.1080/14737175.2024.2442658] [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: 09/09/2024] [Revised: 10/31/2024] [Accepted: 12/05/2024] [Indexed: 12/21/2024]
Abstract
INTRODUCTION Post-traumatic stress disorder (PTSD) can have debilitating effects on quality of life, and conventional treatments show mixed results. Neuromodulation is emerging as a promising approach for treating PTSD. This review examines current neuromodulatory treatments for PTSD, and highlights methodologies, clinical outcomes, and gaps in the literature to help guide future research. AREAS COVERED A PubMed search identified 252 studies on PTSD and neuromodulation, of which 61 were selected for full review. These included 37 studies on repetitive transcranial magnetic stimulation (rTMS), 10 on transcranial direct current stimulation (tDCS),4 on deep brain stimulation (DBS) and 2 on focused ultrasound (FUS). EXPERT OPINION The present review supports the potential of neuromodulation to reduce PTSD symptoms. rTMS and tDCS targeting the dlPFC appear effective through modulating neural circuits involved in fear processing and conditioning, however, literature varies regarding efficacy of stimulation frequencies and hemispheric targets. DBS targeting the amygdala or subcallosal cingulate white matter tracts improves treatment of refractory PTSD with sustained benefits, while FUS may improve symptoms through targeted modulation of brain structures such as the amygdala, though this technique is in the early stages of exploration. Future research should refine established neuromodulatory approaches and address gaps in emerging modalities to enhance treatment efficacy.
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Affiliation(s)
- Felicia Manocchio
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
| | - Jordan Enepekides
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
| | - Sean Nestor
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Peter Giacobbe
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Jennifer S Rabin
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Matthew J Burke
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Krista L Lanctôt
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Maged Goubran
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Ying Meng
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Nir Lipsman
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Clement Hamani
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Benjamin Davidson
- Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
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Chmiel J, Stępień-Słodkowska M. Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Bulimia Nervosa (BN): A Review and Insight into Potential Mechanisms of Action. J Clin Med 2024; 13:5364. [PMID: 39336850 PMCID: PMC11432543 DOI: 10.3390/jcm13185364] [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: 08/20/2024] [Revised: 09/08/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
INTRODUCTION Bulimia nervosa (BN) is a disorder primarily affecting adolescent females, characterized by episodes of binge eating followed by inappropriate compensatory behaviors aimed at preventing weight gain, including self-induced vomiting and the misuse of diuretics, laxatives, and insulin. The precise etiology of BN remains unknown, with factors such as genetics, biological influences, emotional disturbances, societal pressures, and other challenges contributing to its prevalence. First-line treatment typically includes pharmacotherapy, which has shown moderate effectiveness. Neuroimaging evidence suggests that altered brain activity may contribute to the development of BN, making interventions that directly target the brain extremely valuable. One such intervention is repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique that has been garnering interest in the medical community for many years. METHODS This review explores the use of rTMS in the treatment of BN. Searches were conducted in the PubMed/Medline, ResearchGate, and Cochrane databases. RESULTS Twelve relevant studies were identified. Analysis of the results from these studies reveals promising findings, particularly regarding key parameters in the pathophysiology of BN. Several studies assessed the impact of rTMS on binge episodes. While some studies did not find significant reductions, most reported decreases in binge eating and purging behaviors, with some cases showing complete remission. Reductions in symptoms of depression and food cravings were also demonstrated. However, results regarding cognitive improvement were mixed. The discussion focused heavily on potential mechanisms of action, including neuromodulation of brain networks, induction of neuroplasticity, impact on serotonergic dysfunction, anti-inflammatory action, and HPA axis modulation. rTMS was found to be a safe intervention with no serious side effects. CONCLUSIONS rTMS in the treatment of BN appears to be a promising intervention that alleviates some symptoms characteristic of the pathophysiology of this disorder. An additional effect is a significant reduction in depressive symptoms. However, despite these findings, further research is required to confirm its effectiveness and elucidate the mechanisms of action. It is also recommended to further investigate the potential mechanisms of action described in this review.
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Affiliation(s)
- James Chmiel
- Faculty of Physical Culture and Health, Institute of Physical Culture Sciences, University of Szczecin, Al. Piastów 40B blok 6, 71-065 Szczecin, Poland
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Davani AJ, Richardson AJ, Vodovozov W, Sanghani SN. Neuromodulation in Psychiatry. ADVANCES IN PSYCHIATRY AND BEHAVIORAL HEALTH 2024; 4:177-198. [DOI: 10.1016/j.ypsc.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Zorns S, Sierzputowski C, Ash S, Skowron M, Minervini A, LaVarco A, Pardillo M, Keenan JP. Attraction is altered via modulation of the medial prefrontal cortex without explicit knowledge. Front Hum Neurosci 2024; 18:1333733. [PMID: 39206424 PMCID: PMC11349520 DOI: 10.3389/fnhum.2024.1333733] [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: 11/05/2023] [Accepted: 06/04/2024] [Indexed: 09/04/2024] Open
Abstract
Previous studies have demonstrated that brain stimulation can alter an individual's physical appearance via dysregulation of the medial prefrontal cortex (MPFC). In this study, we attempted to determine if individuals who receive repetitive transcranial magnetic stimulation (rTMS) delivered to the MPFC were rated as more attractive by others. It has been previously reported that 1 hertz (Hz) (inhibitory) TMS can alter one's facial expressions such that frontal cortex inhibition can increase expressiveness. These alterations, detected by external observation, remain below the level of awareness of the subject itself. In Phase I, subjects (N = 10) received MPFC rTMS and had their photographs taken after each of the five stimulation conditions, in addition to making self-ratings across a number of variables, including attractiveness. In Phase II, participants (N = 430) rated five pictures of each of the Phase 1 individuals on attractiveness. It was found that there were no significant differences in self-assessment following rTMS (Phase I). However, attractiveness ratings differed significantly in Phase II. There was a significant difference found between 10 Hz TMS delivered to the MPFC (p < 0.001), such that individuals were rated as less attractive. Furthermore, 1 Hz TMS to the MPFC increased the number of 'Most Attractive' ratings, while 10Hz TMS decreased the number of 'Most Attractive' ratings (p < 0.001). These results suggest that the MPFC plays a role in attractiveness ratings to others. These data also support research showing that one's appearance can be altered below the level of awareness via rTMS. To our knowledge, this is the first investigation to examine how brain stimulation influences one's attractiveness.
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Affiliation(s)
- Samantha Zorns
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Claudia Sierzputowski
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Sydney Ash
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Molly Skowron
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Anthony Minervini
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Adriana LaVarco
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Matthew Pardillo
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
| | - Julian Paul Keenan
- Cognitive Neuroimaging Laboratory, Montclair State University, Montclair, NJ, United States
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Brown R, Cherian K, Jones K, Wickham R, Gomez R, Sahlem G. Repetitive transcranial magnetic stimulation for post-traumatic stress disorder in adults. Cochrane Database Syst Rev 2024; 8:CD015040. [PMID: 39092744 PMCID: PMC11295260 DOI: 10.1002/14651858.cd015040.pub2] [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] [Indexed: 08/04/2024]
Abstract
BACKGROUND The estimated lifetime prevalence of post-traumatic stress disorder (PTSD) in adults worldwide has been estimated at 3.9%. PTSD appears to contribute to alterations in neuronal network connectivity patterns. Current pharmacological and psychotherapeutic treatments for PTSD are associated with inadequate symptom improvement and high dropout rates. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive therapy involving induction of electrical currents in cortical brain tissue, may be an important treatment option for PTSD to improve remission rates and for people who cannot tolerate existing treatments. OBJECTIVES To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on post-traumatic stress disorder (PTSD) in adults. SEARCH METHODS We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two clinical trials registers. We checked reference lists of relevant articles. The most recent search was January 2023. SELECTION CRITERIA We included randomized controlled trials (RCTs) assessing the efficacy and safety of rTMS versus sham rTMS for PTSD in adults from any treatment setting, including veterans. Eligible trials employed at least five rTMS treatment sessions with both active and sham conditions. We included trials with combination interventions, where a pharmacological agent or psychotherapy was combined with rTMS for both intervention and control groups. We included studies meeting the above criteria regardless of whether they reported any of our outcomes of interest. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the risk of bias in accordance with Cochrane standards. Primary outcomes were PTSD severity immediately after treatment and serious adverse events during active treatment. Secondary outcomes were PTSD remission, PTSD response, PTSD severity at two follow-up time points after treatment, dropouts, and depression and anxiety severity immediately after treatment. MAIN RESULTS We included 13 RCTs in the review (12 published; 1 unpublished dissertation), with 577 participants. Eight studies included stand-alone rTMS treatment, four combined rTMS with an evidence-based psychotherapeutic treatment, and one investigated rTMS as an adjunctive to treatment-as-usual. Five studies were conducted in the USA, and some predominantly included white, male veterans. Active rTMS probably makes little to no difference to PTSD severity immediately following treatment (standardized mean difference (SMD) -0.14, 95% confidence interval (CI) -0.54 to 0.27; 3 studies, 99 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision (sample size insufficient to detect a difference of medium effect size). We deemed one study as having a low risk of bias and the remaining two as having 'some concerns' for risk of bias. A sensitivity analysis of change-from-baseline scores enabled inclusion of a greater number of studies (6 studies, 252 participants). This analysis yielded a similar outcome to our main analysis but also indicated significant heterogeneity in efficacy across studies, including two studies with a high risk of bias. Reported rates of serious adverse events were low, with seven reported (active rTMS: 6; sham rTMS: 1). The evidence is very uncertain about the effect of active rTMS on serious adverse events (odds ratio (OR) 5.26, 95% CI 0.26 to 107.81; 5 studies, 251 participants; very low-certainty evidence [Active rTMS: 23/1000, sham rTMS: 4/1000]). We downgraded the evidence by one level for risk of bias and two levels for imprecision. We rated four of five studies as having a high risk of bias, and the fifth as 'some concerns' for bias. We were unable to assess PTSD remission immediately after treatment as none of the included studies reported this outcome. AUTHORS' CONCLUSIONS Based on moderate-certainty evidence, our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation. However, significant heterogeneity in efficacy was detected when we included a larger number of studies in sensitivity analysis. We observed considerable variety in participant and protocol characteristics across studies included in this review. For example, studies tended to be weighted towards inclusion of either male veterans or female civilians. Studies varied greatly in terms of the proportion of the sample with comorbid depression. Study protocols differed in treatment design and stimulation parameters (e.g. session number/duration, treatment course length, stimulation intensity/frequency, location of stimulation). These differences may affect efficacy, particularly when considering interactions with participant factors. Reported rates of serious adverse events were very low (< 1%) across active and sham conditions. It is uncertain whether rTMS increases the risk of serious adverse event occurrence, as our certainty of evidence was very low. Studies frequently lacked clear definitions for serious adverse events, as well as detail on tracking/assessment of data and information on the safety population. Increased reporting on these elements would likely aid the advancement of both research and clinical recommendations of rTMS for PTSD. Currently, there is insufficient evidence to meta-analyze PTSD remission, PTSD treatment response, and PTSD severity at different periods post-treatment. Further research into these outcomes could inform the clinical use of rTMS. Additionally, the relatively large contribution of data from trials that focused on white male veterans may limit the generalizability of our conclusions. This could be addressed by prioritizing recruitment of more diverse participant samples.
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Affiliation(s)
- Randi Brown
- Clinical Psychology, Palo Alto University, Palo Alto, CA, USA
| | - Kirsten Cherian
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Katherine Jones
- Sheffield Centre for Health and Related Research, University of Sheffield, Sheffield, UK
| | - Robert Wickham
- Department of Psychological Sciences, Northern Arizona University, Flagstaff, AZ, USA
| | - Rowena Gomez
- Clinical Psychology, Palo Alto University, Palo Alto, CA, USA
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Gregory Sahlem
- Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
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Faerman A, Buchanan DM, Williams NR. Transcranial magnetic stimulation as a countermeasure for behavioral and neuropsychological risks of long-duration and deep-space missions. NPJ Microgravity 2024; 10:58. [PMID: 38806522 PMCID: PMC11133369 DOI: 10.1038/s41526-024-00401-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 05/05/2024] [Indexed: 05/30/2024] Open
Affiliation(s)
- Afik Faerman
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
| | - Derrick M Buchanan
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Nolan R Williams
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
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Rezaei M, Bagheri MMS. Clinical effects of anodal tDCS and identifying response markers in post-traumatic stress disorder (PTSD): An open-label study. Behav Brain Res 2024; 458:114751. [PMID: 37931705 DOI: 10.1016/j.bbr.2023.114751] [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: 07/31/2023] [Revised: 11/02/2023] [Accepted: 11/03/2023] [Indexed: 11/08/2023]
Abstract
Transcranial direct current stimulation (tDCS) is a promising treatment for post-traumatic stress disorder (PTSD). However, not all patients respond to this type of treatment. The first aim of present study was to examine efficacy of tDCS for PTSD, depression, anxiety, and anhedonia in patients with PTSD. The second aim of this study was to examine the demographic, clinical, and psychological factors that may predict response to tDCS. In this open-label study, 103 PTSD patients underwent 10 sessions of tDCS (2 mA, 20 min). The anodal and cathodal electrodes were placed over the left dorsolateral prefrontal cortex (DLPFC; F3) and right supra-orbital (FP2) Respectively. Clinical outcome measures included Posttraumatic the Stress Disorder Checklist for DSM-5 (PCL-5), the Beck Depression Inventory (BDI-II), the Beck Anxiety Inventory (BAI), and the Snaith-Hamilton Pleasure Scale (SHAPS). There was an overall significant improvement in symptoms of PTSD, depression, anxiety, and anhedonia from pre- to post-treatment. Results also revealed that non-responders had higher severity at baseline for depression, anxiety, and anhedonia. However, higher severity of depression and anhedonia at baseline predicted response status, with higher severity associated with greater likelihood of non-response. tDCS of the left dLPFC and right supra-orbital appears to have a positive effect in reducing PTSD and related symptoms. These initial results could have an important influence on the adoption of anodal tDCS over the left DLPFC for PTSD, by enabling the early identification of patients who respond to tDCS.
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Affiliation(s)
- Mehdi Rezaei
- Department of Psychology, Faculty of Educational Sciences and Psychology, University of Birjand, Birjand, Iran.
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11
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Xu G, Li G, Yang Q, Li C, Liu C. Explore the durability of repetitive transcranial magnetic stimulation in treating post-traumatic stress disorder: An updated systematic review and meta-analysis. Stress Health 2024; 40:e3292. [PMID: 37452747 DOI: 10.1002/smi.3292] [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: 02/20/2023] [Revised: 06/27/2023] [Accepted: 07/05/2023] [Indexed: 07/18/2023]
Abstract
The objective was to synthesize results from studies that assessed symptom relief after repetitive transcranial magnetic stimulation (rTMS) treatment for post-traumatic stress disorder (PTSD) and investigate the long-term effectiveness of rTMS for treating PTSD. We searched multiple databases for relevant randomized controlled trials of rTMS for PTSD treatment up to 1 January 2023. Two researchers evaluated the studies and focused on the CAPS and PCL as outcome indicators. We used STATA17 SE software for the data analysis. Eight articles involving 309 PTSD patients were analysed in a meta-analysis, which found that rTMS had a significant and large effect on reducing core post-traumatic symptoms [Hedges'g = 1.75, 95% CI (1.18, 2.33)]. Both low and high-frequency rTMS also significantly reduced symptoms, with the latter having a greater effect. rTMS was shown to have a long-term effect on PTSD, with all three subgroup analyses demonstrating significant results. Interestingly, no significant difference in symptom relief was found between the follow-up and completion of treatments [Hedges'g = 0.01, 95% CI (-0.30, 0.33)], suggesting that the treatment effect of rTMS is stable. The meta-analysis provides strong evidence that rTMS is effective in reducing the severity and symptoms of PTSD in patients, and follow-up studies confirm its long-term stability.
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Affiliation(s)
- Guobin Xu
- Clinical College, Southwest Medical University, Luzhou, Sichuan, China
| | - Geng Li
- School of Physical Education, Hunan Normal University, Changsha, Hunan, China
| | - Qizhang Yang
- Clinical College, Southwest Medical University, Luzhou, Sichuan, China
| | - Chao Li
- Clinical College, Southwest Medical University, Luzhou, Sichuan, China
| | - Chengzhen Liu
- School of Humanities and Management Science, Southwest Medical University, Luzhou, Sichuan, China
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12
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Vasileva AV. [Posttraumatic stress disorder clinical guidelines and treatment standards: focus on the symptoms of the psychophysiological arousal]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:58-68. [PMID: 38884431 DOI: 10.17116/jnevro202412405158] [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] [Indexed: 06/18/2024]
Abstract
The article describes the main diagnostic criteria and principles of posttraumatic stress disorder (PTSD) diagnostic with the consideration of risk factors and specific clinical features. The main biomarkers search trends and existing limitations are considered. The role of the psychophysiological arousal symptoms claster is highlighted in the clinical picture of PTSD as well as in connection with the main cluster of re-experiencing symptoms activation and slowing of sanogenesis process. The necessity of PTSD detection in somatic medicine is thoroughly described. The article presents therapeutic algorithms of the latest international and Russian PTSD treatment clinical guidelines based on the individual combination of psychotherapy and psychopharmacotherapy treatment choice. Additionally the accumulated during the last decades national clinical experience of the anxiety disorders treatment, including the symptoms of psychophysiological arousal is highlighted that determined the list of the recommended drugs indicating the evidence level, in the PTSD treatment standards and guidelines. The treatment choices possibilities with the consideration of different PTSD symptoms cluster expression and comorbid states and individual case distress level specific are presented. Main evidence based psychotherapeutic methods are described.
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Affiliation(s)
- A V Vasileva
- Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia
- Mechnikov North-Western State Medical University, St. Petersburg, Russia
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13
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Yuan H, Liu B, Li F, Jin Y, Zheng S, Ma Z, Wu Z, Chen C, Zhang L, Gu Y, Gao X, Yang Q. Effects of intermittent theta-burst transcranial magnetic stimulation on post-traumatic stress disorder symptoms: A randomized controlled trial. Psychiatry Res 2023; 329:115533. [PMID: 37826976 DOI: 10.1016/j.psychres.2023.115533] [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: 05/18/2023] [Revised: 10/04/2023] [Accepted: 10/06/2023] [Indexed: 10/14/2023]
Abstract
Post-traumatic stress disorder (PTSD) is a prevalent and debilitating illness, which can be alleviated by transcranial magnetic stimulation (TMS). Intermittent theta burst stimulation (iTBS), a newer form of repetitive transcranial magnetic stimulation (rTMS), offers the advantage of shorter treatment sessions compared to the standard 10 Hz rTMS treatment. In order to compare the two forms of TMS, we enrolled 75 participants aged between 18 and 55 years who presented with (PCL-C) scale score of at least 50. Participants were randomly assigned to groups in a ratio of 1:1:1, receiving either 10 Hz rTMS, iTBS, or sham-controlled iTBS. Participants in the two treatment groups underwent 15 therapies which consisted of 1800 pulses and targeted the right dorsolateral prefrontal cortex (DLPFC). The main outcomes included changes in scores on the PCL-C and the Post-Traumatic Growth Inventory (PTGI). After intervention, the PCL-C and PTGI scores in iTBS and rTMS groups were significantly different from those in sham-controlled iTBS group. No significant differences in PCL-C and PTGI were found between the two active treatment groups. ITBS, with a shorter treatment duration, can effectively improve the symptoms of PTSD, with no significant difference in effect from that of rTMS. Future studies need to further elucidate the mechanisms, optimize the parameters and investigate the therapeutic potential and efficacy of iTBS in PTSD.
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Affiliation(s)
- Huiling Yuan
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China; Department of Psychiatry, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, China
| | - Bin Liu
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Fengzhan Li
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Yinchuan Jin
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Shi Zheng
- State key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China
| | - Zhujing Ma
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Zhongying Wu
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Chen Chen
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Liang Zhang
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Yanan Gu
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Xing Gao
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China
| | - Qun Yang
- Department of Military Medical Psychology, Air Force Medical University, Xi'an 710032, China.
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14
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Ferreri F, Mouchabac S, Sylvestre V, Millet B, El Hage W, Adrien V, Bourla A. Repetitive Transcranial Magnetic Stimulation (rTMS) in Post-Traumatic Stress Disorder: Study Protocol of a Nationwide Randomized Controlled Clinical Trial of Neuro-Enhanced Psychotherapy "TraumaStim". Brain Sci 2023; 13:1274. [PMID: 37759875 PMCID: PMC10526173 DOI: 10.3390/brainsci13091274] [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: 08/04/2023] [Revised: 08/24/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
The use of high-frequency Transcranial Magnetic Stimulation (HF-rTMS) of the right dorsolateral prefrontal cortex (DLPFC) in treating Post-traumatic Stress Disorder (PTSD) is currently regarded as a level B intervention (probable effectiveness). HF-rTMS has attracted interest as a neuromodulation therapeutic method for PTSD. Prolonged exposure and reactivation therapy are also regarded as first-line treatments for PTSD. Randomized controlled clinical studies examining the effectiveness of several HF-rTMS sessions coupled with psychotherapy have not yet been completed. In total, 102 patients with refractory PTSD will be randomly assigned (1:1) to reactivation therapy, in addition to either active HF-rTMS (20 Hz) or sham HF-rTMS, for 12 sessions in a nationwide, multicenter, double-blind controlled trial. The impact on PTSD symptoms and neurocognitive functioning will be assessed. The primary outcome is the PTSD severity score measured based on the Clinician-Administered PTSD Scale (CAPS-5) at one month. If this additional therapy is successful, it may strengthen the case for regulatory authorities to approve this additional technique of treating PTSD. Additionally, it expands the field of neurostimulation-assisted psychotherapy.
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Affiliation(s)
- Florian Ferreri
- Department of Psychiatry, Hôpital Saint-Antoine, Sorbonne Université, AP-HP, 75012 Paris, France; (F.F.); (S.M.); (V.A.)
- ICRIN—Psychiatry (Infrastructure of Clinical Research in Neurosciences—Psychiatry), Brain Institute (ICM), Sorbonne Université, INSERM, CNRS, 75013 Paris, France;
| | - Stephane Mouchabac
- Department of Psychiatry, Hôpital Saint-Antoine, Sorbonne Université, AP-HP, 75012 Paris, France; (F.F.); (S.M.); (V.A.)
- ICRIN—Psychiatry (Infrastructure of Clinical Research in Neurosciences—Psychiatry), Brain Institute (ICM), Sorbonne Université, INSERM, CNRS, 75013 Paris, France;
| | - Vincent Sylvestre
- Department of Psychiatry, Hôpital Saint-Antoine, Sorbonne Université, AP-HP, 75012 Paris, France; (F.F.); (S.M.); (V.A.)
| | - Bruno Millet
- ICRIN—Psychiatry (Infrastructure of Clinical Research in Neurosciences—Psychiatry), Brain Institute (ICM), Sorbonne Université, INSERM, CNRS, 75013 Paris, France;
- Service de Psychiatrie Adulte de la Pitié-Salpêtrière, Sorbonne Université, AP-HP, 75013 Paris, France
| | - Wissam El Hage
- Centre Régional de Psychotraumatologie CVL, CHRU de Tours, UMR 1253, iBrain, Université de Tours, INSERM, 37000 Tours, France;
| | - Vladimir Adrien
- Department of Psychiatry, Hôpital Saint-Antoine, Sorbonne Université, AP-HP, 75012 Paris, France; (F.F.); (S.M.); (V.A.)
- ICRIN—Psychiatry (Infrastructure of Clinical Research in Neurosciences—Psychiatry), Brain Institute (ICM), Sorbonne Université, INSERM, CNRS, 75013 Paris, France;
| | - Alexis Bourla
- Department of Psychiatry, Hôpital Saint-Antoine, Sorbonne Université, AP-HP, 75012 Paris, France; (F.F.); (S.M.); (V.A.)
- ICRIN—Psychiatry (Infrastructure of Clinical Research in Neurosciences—Psychiatry), Brain Institute (ICM), Sorbonne Université, INSERM, CNRS, 75013 Paris, France;
- Clariane, Medical Strategy and Innovation Department, 75008 Paris, France
- NeuroStim Psychiatry Practice, 75005 Paris, France
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Michel-Flutot P, Lane MA, Lepore AC, Vinit S. Therapeutic Strategies Targeting Respiratory Recovery after Spinal Cord Injury: From Preclinical Development to Clinical Translation. Cells 2023; 12:1519. [PMID: 37296640 PMCID: PMC10252981 DOI: 10.3390/cells12111519] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/15/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023] Open
Abstract
High spinal cord injuries (SCIs) lead to permanent functional deficits, including respiratory dysfunction. Patients living with such conditions often rely on ventilatory assistance to survive, and even those that can be weaned continue to suffer life-threatening impairments. There is currently no treatment for SCI that is capable of providing complete recovery of diaphragm activity and respiratory function. The diaphragm is the main inspiratory muscle, and its activity is controlled by phrenic motoneurons (phMNs) located in the cervical (C3-C5) spinal cord. Preserving and/or restoring phMN activity following a high SCI is essential for achieving voluntary control of breathing. In this review, we will highlight (1) the current knowledge of inflammatory and spontaneous pro-regenerative processes occurring after SCI, (2) key therapeutics developed to date, and (3) how these can be harnessed to drive respiratory recovery following SCIs. These therapeutic approaches are typically first developed and tested in relevant preclinical models, with some of them having been translated into clinical studies. A better understanding of inflammatory and pro-regenerative processes, as well as how they can be therapeutically manipulated, will be the key to achieving optimal functional recovery following SCIs.
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Affiliation(s)
- Pauline Michel-Flutot
- END-ICAP, UVSQ, Inserm, Université Paris-Saclay, 78000 Versailles, France;
- Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA;
| | - Michael A. Lane
- Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA;
| | - Angelo C. Lepore
- Department of Neuroscience, Jefferson Synaptic Biology Center, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA;
| | - Stéphane Vinit
- END-ICAP, UVSQ, Inserm, Université Paris-Saclay, 78000 Versailles, France;
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Shenasa MA, Ellerman-Tayag E, Canet P, Martis B, Mishra J, Ramanathan DS. Theta Burst Stimulation Is Not Inferior to High-Frequency Repetitive Transcranial Magnetic Stimulation in Reducing Symptoms of Posttraumatic Stress Disorder in Veterans With Depression: A Retrospective Case Series. Neuromodulation 2023:S1094-7159(23)00135-6. [PMID: 37015842 DOI: 10.1016/j.neurom.2023.02.082] [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: 10/13/2022] [Revised: 02/07/2023] [Accepted: 02/27/2023] [Indexed: 04/06/2023]
Abstract
OBJECTIVES Two commonly used forms of repetitive transcranial magnetic stimulation (rTMS) were recently shown to be equivalent for the treatment of depression: high-frequency stimulation (10 Hz), a protocol that lasts between 19 and 38 minutes, and intermittent theta burst stimulation (iTBS), a protocol that can be delivered in just three minutes. However, it is unclear whether iTBS treatment offers the same benefits as those of standard 10-Hz rTMS for comorbid symptoms such as those seen in posttraumatic stress disorder (PTSD). MATERIALS AND METHODS In this retrospective case series, we analyzed treatment outcomes in veterans from the Veterans Affairs San Diego Healthcare System who received 10-Hz (n = 47) or iTBS (n = 51)-rTMS treatments for treatment-resistant depression between February 2018 and June 2022. We compared outcomes between these two stimulation protocols in symptoms of depression (using changes in the Patient Health Questionnaire-9 [PHQ-9]) and PTSD (using changes in the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, or Patient Checklist [PCL]-5). RESULTS There was an imbalance of sex between groups (p < 0.05). After controlling for sex, we found no significant difference by stimulation protocol for depression (PHQ-9, F [1,94] = 0.16, p = 0.69, eta-squared = 0.002), confirming the original study previously noted. We also showed no difference by stimulation protocol of changes in PTSD symptoms (PCL-5, F [1,94] = 3.46, p = 0.067, eta-squared = 0.036). The iTBS group showed a decrease from 41.9 ± 4.4 to 25.1 ± 4.9 (a difference of 16.8 points) on the PCL-5 scale whereas the 10-Hz group showed a decrease from 43.6 ± 2.9 to 35.2 ± 3.2 on this scale (a difference of 8.4 points). Follow-up analyses restricting the sample in various ways did not meaningfully change these results (no follow-up analyses showed that there was a significant difference between stimulation protocols). CONCLUSIONS Although limited by small sample size, nonblind, and pseudorandomized assignment, our data suggest that iTBS is similar to 10-Hz stimulation in inducing reductions in PTSD symptoms and depression in military veterans.
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Affiliation(s)
- Mohammad Ali Shenasa
- Mental Health Care Line, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Em Ellerman-Tayag
- Mental Health Care Line, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
| | - Philippe Canet
- Mental Health Care Line, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
| | - Brian Martis
- Mental Health Care Line, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Jyoti Mishra
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Dhakshin S Ramanathan
- Mental Health Care Line, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Center of Excellence for Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
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17
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Chou PH, Wang SC, Wu CS, Ito M. Trauma-related guilt as a mediator between post-traumatic stress disorder and suicidal ideation. Front Psychiatry 2023; 14:1131733. [PMID: 37056401 PMCID: PMC10086326 DOI: 10.3389/fpsyt.2023.1131733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 03/13/2023] [Indexed: 04/15/2023] Open
Abstract
Background As a mental health issue, suicide is a growing global concern, with patients who have post-traumatic stress disorder (PTSD) being at particularly high risk. This study aimed to investigate whether the link between PTSD and suicidal ideation is mediated by trauma-related guilt. Methods Data were obtained from Wave 1, Time 1 (November 2016), and Time 2 (March 2017) of the National Survey for Stress and Health (NSSH) in Japan. The NSSH is an online longitudinal survey conducted on Japan's national population aged 18 years and older. The cumulative response rate of the survey was 66.7% at Time 2. A total of 1,005 patients with PTSD were included for analyses. The severity of PTSD symptoms was assessed with PTSD DSM-5 Checklist, and the trauma-related guilt were assessed using the two subscales (hindsight-bias/responsibility and global guilt scale) of the trauma-related guilt inventory (TRGI). Suicidal ideation was evaluated using the suicidal ideation attributes scale (SIDAS). Pearson's correlation was used to investigate the associations among PTSD symptoms, TRGI scores, and SIDAS scores. Causal mediation analysis was applied to evaluate the causal relationship between PTSD, trauma-related guilt, and suicidal ideation. Results Pearson's correlation did not show patients' age, gender, and household income significantly associated with SIDAS scores. On the other hand, severities of PTSD symptoms (r = 0.361, p < 0.001) and trauma-related guilt (r = 0.235, p < 0.001) were positively associated with SIDAS scores. After adjusting for age, gender, and household income, the mediation analysis revealed that trauma-related guilt significantly mediates the effects of PTSD symptoms on suicidal ideation. Conclusion Our results implied that trauma-related guilt may represent a critical link between PTSD and suicidal ideation, which may be a noteworthy target for therapeutic intervention.
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Affiliation(s)
- Po-Han Chou
- Department of Psychiatry, China Medical University Hsinchu Hospital, China Medical University, Taichung, Taiwan
- Department of Psychiatry, China Medical University Hospital, China Medical University, Taichung, Taiwan
- *Correspondence: Po-Han Chou, ;
| | - Shao-Cheng Wang
- Department of Psychiatry, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
- Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan
- Department of Nurse-Midwifery and Women Health, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Chi-Shin Wu
- National Center for Geriatrics and Welfare Research, National Health Research Institutes, Miaoli, Taiwan
- Department of Psychiatry, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
- Chi-Shin Wu,
| | - Masaya Ito
- National Center for Cognitive-Behavior Therapy and Research, National Center of Neurology and Psychiatry, Hsinchu, Miaoli, Taiwan
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18
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Becker CR, Milad MR. Contemporary Approaches Toward Neuromodulation of Fear Extinction and Its Underlying Neural Circuits. Curr Top Behav Neurosci 2023; 64:353-387. [PMID: 37658219 DOI: 10.1007/7854_2023_442] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/03/2023]
Abstract
Neuroscience and neuroimaging research have now identified brain nodes that are involved in the acquisition, storage, and expression of conditioned fear and its extinction. These brain regions include the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), amygdala, insular cortex, and hippocampus. Psychiatric neuroimaging research shows that functional dysregulation of these brain regions might contribute to the etiology and symptomatology of various psychopathologies, including anxiety disorders and post traumatic stress disorder (PTSD) (Barad et al. Biol Psychiatry 60:322-328, 2006; Greco and Liberzon Neuropsychopharmacology 41:320-334, 2015; Milad et al. Biol Psychiatry 62:1191-1194, 2007a, Biol Psychiatry 62:446-454, b; Maren and Quirk Nat Rev Neurosci 5:844-852, 2004; Milad and Quirk Annu Rev Psychol 63:129, 2012; Phelps et al. Neuron 43:897-905, 2004; Shin and Liberzon Neuropsychopharmacology 35:169-191, 2009). Combined, these findings indicate that targeting the activation of these nodes and modulating their functional interactions might offer an opportunity to further our understanding of how fear and threat responses are formed and regulated in the human brain, which could lead to enhancing the efficacy of current treatments or creating novel treatments for PTSD and other psychiatric disorders (Marin et al. Depress Anxiety 31:269-278, 2014; Milad et al. Behav Res Ther 62:17-23, 2014). Device-based neuromodulation techniques provide a promising means for directly changing or regulating activity in the fear extinction network by targeting functionally connected brain regions via stimulation patterns (Raij et al. Biol Psychiatry 84:129-137, 2018; Marković et al. Front Hum Neurosci 15:138, 2021). In the past ten years, notable advancements in the precision, safety, comfort, accessibility, and control of administration have been made to the established device-based neuromodulation techniques to improve their efficacy. In this chapter we discuss ten years of progress surrounding device-based neuromodulation techniques-Electroconvulsive Therapy (ECT), Transcranial Magnetic Stimulation (TMS), Magnetic Seizure Therapy (MST), Transcranial Focused Ultrasound (TUS), Deep Brain Stimulation (DBS), Vagus Nerve Stimulation (VNS), and Transcranial Electrical Stimulation (tES)-as research and clinical tools for enhancing fear extinction and treating PTSD symptoms. Additionally, we consider the emerging research, current limitations, and possible future directions for these techniques.
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Affiliation(s)
- Claudia R Becker
- Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, USA
| | - Mohammed R Milad
- Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, USA.
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Camacho‐Conde JA, del Rosario Gonzalez‐Bermudez M, Carretero‐Rey M, Khan ZU. Therapeutic potential of brain stimulation techniques in the treatment of mental, psychiatric, and cognitive disorders. CNS Neurosci Ther 2022; 29:8-23. [PMID: 36229994 PMCID: PMC9804057 DOI: 10.1111/cns.13971] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 02/06/2023] Open
Abstract
Treatment for brain diseases has been disappointing because available medications have failed to produce clinical response across all the patients. Many patients either do not respond or show partial and inconsistent effect, and even in patients who respond to the medications have high relapse rates. Brain stimulation has been seen as an alternative and effective remedy. As a result, brain stimulation has become one of the most valuable therapeutic tools for combating against brain diseases. In last decade, studies with the application of brain stimulation techniques not only have grown exponentially but also have expanded to wide range of brain disorders. Brain stimulation involves passing electric currents into the cortical and subcortical area brain cells with the use of noninvasive as well as invasive methods to amend brain functions. Over time, technological advancements have evolved into the development of precise devices; however, at present, most used noninvasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In the current review, we will provide an overview of the potential of noninvasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques focusing on the treatment of mental, psychiatric, and cognitive disorders.
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Affiliation(s)
- Jose Antonio Camacho‐Conde
- Laboratory of Neurobiology, CIMESUniversity of Malaga, Campus Teatinos s/nMalagaSpain,Department of Medicine, Faculty of MedicineUniversity of Malaga, Campus Teatinos s/nMalagaSpain
| | | | - Marta Carretero‐Rey
- Laboratory of Neurobiology, CIMESUniversity of Malaga, Campus Teatinos s/nMalagaSpain,Department of Medicine, Faculty of MedicineUniversity of Malaga, Campus Teatinos s/nMalagaSpain
| | - Zafar U. Khan
- Laboratory of Neurobiology, CIMESUniversity of Malaga, Campus Teatinos s/nMalagaSpain,Department of Medicine, Faculty of MedicineUniversity of Malaga, Campus Teatinos s/nMalagaSpain,CIBERNEDInstitute of Health Carlos IIIMadridSpain
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20
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Rosson S, de Filippis R, Croatto G, Collantoni E, Pallottino S, Guinart D, Brunoni AR, Dell'Osso B, Pigato G, Hyde J, Brandt V, Cortese S, Fiedorowicz JG, Petrides G, Correll CU, Solmi M. Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review. Neurosci Biobehav Rev 2022; 139:104743. [PMID: 35714757 DOI: 10.1016/j.neubiorev.2022.104743] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/07/2022] [Accepted: 06/10/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING None.
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Affiliation(s)
- Stella Rosson
- Department of Mental Health, Azienda ULSS 3 Serenissima, Venice, Italy; Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Department of Neurosciences, University of Padua, Padua, Italy
| | - Renato de Filippis
- Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giovanni Croatto
- Department of Mental Health, Azienda ULSS 3 Serenissima, Venice, Italy; Department of Neurosciences, University of Padua, Padua, Italy
| | | | | | - Daniel Guinart
- Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Neuropsiquiatria i Addiccions (INAD), Hospital del Mar, Institut Hospital del Mard'Investigacions Mèdiques (IMIM), Barcelona, Spain
| | - Andre R Brunoni
- Service of Interdisciplinary Neuromodulation (SIN), Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da USP, Brazil; Departamentos de Clínica Médica e Psiquiatria, Faculdade de Medicina da USP, Instituto de Psiquiatria, Hospital das Clínicas da Faculdade de Medicina da USP, Brazil
| | - Bernardo Dell'Osso
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy; Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford University, Stanford, CA, USA; Aldo Ravelli" Center for Nanotechnology and Neurostimulation, University of Milan, Milan, Italy
| | - Giorgio Pigato
- Department of Neurosciences, University of Padua, Padua, Italy
| | - Joshua Hyde
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
| | - Valerie Brandt
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
| | - Samuele Cortese
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA
| | - Jess G Fiedorowicz
- Department of Psychiatry, University of Ottawa, Ontario, Canada; Department of Mental Health, The Ottawa Hospital, Ontario, Canada
| | - Georgios Petrides
- Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Division of ECT, The Zucker Hillside Hospital, Northwell Health, New York, NY, USA
| | - Christoph U Correll
- Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Germany
| | - Marco Solmi
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK; Department of Psychiatry, University of Ottawa, Ontario, Canada; Department of Mental Health, The Ottawa Hospital, Ontario, Canada; Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Germany; Ottawa Hospital Research Institute (OHRI), Clinical Epidemiology Program University of Ottawa, Ottawa, Ontario, Canada.
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Thierrée S, Raulin-Briot M, Legrand M, Le Gouge A, Vancappel A, Tudorache AC, Brizard B, Clarys D, Caille A, El-Hage W. Combining Trauma Script Exposure With rTMS to Reduce Symptoms of Post-Traumatic Stress Disorder: Randomized Controlled Trial. Neuromodulation 2022; 25:549-557. [PMID: 35667770 DOI: 10.1111/ner.13505] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 06/20/2021] [Accepted: 06/29/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Innovative therapeutic interventions for post-traumatic stress disorder (PTSD) are required. We opted to facilitate fear extinction by combining trauma script exposure with repetitive transcranial magnetic stimulation (rTMS) to reduce symptoms of PTSD. OBJECTIVE The efficacy and safety of 10 Hz rTMS of the right dorsolateral prefrontal cortex simultaneously with exposure to personal traumatic narrative were studied in patients with PTSD. MATERIALS AND METHODS This trial was a single-center randomized controlled trial (NCT02584894). Patients were randomly assigned 1:1 to receive eight daily sessions of 110% of motor threshold high frequency (HF) 10 Hz rTMS (110% HF rTMS) or 70% low frequency (LF) 1 Hz rTMS (70% LF rTMS) with trauma script exposure in both groups. Severity of PTSD, depression, and anxiety were assessed before and after study treatment (one month, three months) by an assessor masked to the trial group assignment. The primary outcome was the severity of PTSD assessed by the Clinician Administered PTSD Scale (CAPS). We used mixed linear regression models for statistical comparisons. RESULTS Thirty-eight patients (65.8% females) were randomly assigned to 110% HF rTMS (n = 18, 31.3 ± 10.0 years, 13 females) or 70% LF rTMS (n = 20, 33.5 ± 11.1 years, 12 females). From baseline to three months, mean CAPS scores decreased by 51% in the 110% HF rTMS group (from 83.7 ± 14.4 to 41.8 ± 31.9) and by 36.9% in the 70% LF rTMS group (from 81.8 ± 15.6 to 51.6 ± 23.7), but with no significant difference in improvement (time by treatment interaction -3.61 [95% confidence interval (CI), -9.70 to 2.47]; p = 0.24; effect size 0.53). One serious adverse event occurred during the study (psychogenic nonepileptic seizure). CONCLUSION We found no evidence of difference in clinical improvement or remission rates between the 110% HF and 70% LF stimulation. These findings may reflect the importance of exposure procedure and that larger number of participants is needed.
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Affiliation(s)
- Sarah Thierrée
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
| | | | - Marc Legrand
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
| | | | - Alexis Vancappel
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France; Clinique Psychiatrique Universitaire, CHRU de Tours, Tours, France
| | - Andrei-Cristian Tudorache
- UMR CNRS 7295, Centre de Recherches sur la Cognition et l'Apprentissage, Université de Poitiers, Poitiers, France
| | - Bruno Brizard
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
| | - David Clarys
- UMR CNRS 7295, Centre de Recherches sur la Cognition et l'Apprentissage, Université de Poitiers, Poitiers, France
| | - Agnès Caille
- CIC 1415, CHRU Tours, Inserm, Tours, France; SPHERE, UMR 1246, Université de Tours, Université de Nantes, Inserm, Tours, France
| | - Wissam El-Hage
- UMR 1253, iBrain, Université de Tours, Inserm, Tours, France; Clinique Psychiatrique Universitaire, CHRU de Tours, Tours, France; CIC 1415, CHRU Tours, Inserm, Tours, France; CHRU de Tours, CIC 1415, Inserm, Tours, France.
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22
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Du J, Diao H, Zhou X, Zhang C, Chen Y, Gao Y, Wang Y. Post-traumatic stress disorder: a psychiatric disorder requiring urgent attention. MEDICAL REVIEW (BERLIN, GERMANY) 2022; 2:219-243. [PMID: 37724188 PMCID: PMC10388753 DOI: 10.1515/mr-2022-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 06/21/2022] [Indexed: 09/20/2023]
Abstract
Post-traumatic stress disorder (PTSD) is a severe and heterogenous psychiatric disorder that was first defined as a mental disorder in 1980. Currently, the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and the International Classification of Diseases 11th Edition (ICD-11) offer the most widely accepted diagnostic guidelines for PTSD. In both diagnostic categories, experiencing a traumatic event (TE) is the necessary criterion for diagnosing PTSD. The TEs described in the DSM-5 include actual or threatened death, serious injury, sexual violence, and other extreme stressors, either directly or indirectly. More than 70% of adults worldwide are exposed to a TE at least once in their lifetime, and approximately 10% of individuals develop PTSD after experiencing a TE. The important features of PTSD are intrusion or re-experiencing fear memories, pervasive sense of threat, active avoidance, hyperarousal symptoms, and negative alterations of cognition and mood. Individuals with PTSD have high comorbidities with other psychiatric diseases, including major depressive disorder, generalized anxiety disorder, and substance use disorder. Multiple lines of evidence suggest that the pathophysiology of PTSD is complex, involving abnormal neural circuits, molecular mechanisms, and genetic mechanisms. A combination of both psychotherapy and pharmacotherapy is used to treat PTSD, but has limited efficacy in patients with refractory PTSD. Because of the high prevalence, heavy burden, and limited treatments, PTSD is a psychiatric disorder that requires urgent attention. In this review, we summarize and discuss the diagnosis, prevalence, TEs, pathophysiology, and treatments of PTSD and draw attention to its prevention.
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Affiliation(s)
- Jun Du
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Huapeng Diao
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Xiaojuan Zhou
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Chunkui Zhang
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Yifei Chen
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Yan Gao
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Yizheng Wang
- The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing, China
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23
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Effects of Chronic High-Frequency rTMS Protocol on Respiratory Neuroplasticity Following C2 Spinal Cord Hemisection in Rats. BIOLOGY 2022; 11:biology11030473. [PMID: 35336846 PMCID: PMC8945729 DOI: 10.3390/biology11030473] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/14/2022] [Accepted: 03/16/2022] [Indexed: 11/22/2022]
Abstract
Simple Summary High spinal cord injuries (SCIs) are known to lead to permanent diaphragmatic paralysis, and to induce deleterious post-traumatic inflammatory processes following cervical spinal cord injury. We used a noninvasive therapeutic tool (repetitive transcranial magnetic stimulation (rTMS)), to harness plasticity in spared descending respiratory circuit and reduce the inflammatory processes. Briefly, the results obtained in this present study suggest that chronic high-frequency rTMS can ameliorate respiratory dysfunction and elicit neuronal plasticity with a reduction in deleterious post-traumatic inflammatory processes in the cervical spinal cord post-SCI. Thus, this therapeutic tool could be adopted and/or combined with other therapeutic interventions in order to further enhance beneficial outcomes. Abstract High spinal cord injuries (SCIs) lead to permanent diaphragmatic paralysis. The search for therapeutics to induce functional motor recovery is essential. One promising noninvasive therapeutic tool that could harness plasticity in a spared descending respiratory circuit is repetitive transcranial magnetic stimulation (rTMS). Here, we tested the effect of chronic high-frequency (10 Hz) rTMS above the cortical areas in C2 hemisected rats when applied for 7 days, 1 month, or 2 months. An increase in intact hemidiaphragm electromyogram (EMG) activity and excitability (diaphragm motor evoked potentials) was observed after 1 month of rTMS application. Interestingly, despite no real functional effects of rTMS treatment on the injured hemidiaphragm activity during eupnea, 2 months of rTMS treatment strengthened the existing crossed phrenic pathways, allowing the injured hemidiaphragm to increase its activity during the respiratory challenge (i.e., asphyxia). This effect could be explained by a strengthening of respiratory descending fibers in the ventrolateral funiculi (an increase in GAP-43 positive fibers), sustained by a reduction in inflammation in the C1–C3 spinal cord (reduction in CD68 and Iba1 labeling), and acceleration of intracellular plasticity processes in phrenic motoneurons after chronic rTMS treatment. These results suggest that chronic high-frequency rTMS can ameliorate respiratory dysfunction and elicit neuronal plasticity with a reduction in deleterious post-traumatic inflammatory processes in the cervical spinal cord post-SCI. Thus, this therapeutic tool could be adopted and/or combined with other therapeutic interventions in order to further enhance beneficial outcomes.
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24
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Stress-related dysautonomias and neurocardiology-based treatment approaches. Auton Neurosci 2022; 239:102944. [DOI: 10.1016/j.autneu.2022.102944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 10/13/2021] [Accepted: 01/16/2022] [Indexed: 11/21/2022]
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Ptito A, Papa L, Gregory K, Folmer RL, Walker WC, Prabhakaran V, Wardini R, Skinner K, Yochelson M. A Prospective, Multicenter Study to Assess the Safety and Efficacy of Translingual Neurostimulation Plus Physical Therapy for the Treatment of a Chronic Balance Deficit Due to Mild-to-Moderate Traumatic Brain Injury. Neuromodulation 2021; 24:1412-1421. [PMID: 32347591 PMCID: PMC9291157 DOI: 10.1111/ner.13159] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 02/28/2020] [Accepted: 03/23/2020] [Indexed: 12/22/2022]
Abstract
OBJECTIVES Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI). MATERIALS AND METHODS This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively. RESULTS The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p < 0.0005). For the pooled population, the SOT responder rate was 67.2% (p < 0.00005), and there were clinically and statistically significant improvements in SOT composite scores after two and five weeks (p < 0.0005). Both groups had reductions in falls and headache disability index scores. Mean dynamic gait index scores in both groups also significantly increased from baseline at weeks 2 and 5. CONCLUSIONS Significant improvements in balance and gait, in addition to headaches, sleep quality, and fall frequency, were observed with TLNS plus targeted PT; in participants who had a chronic balance deficit following an mmTBI and had plateaued on prior conventional physiotherapy.
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Affiliation(s)
- Alain Ptito
- Psychology DepartmentMcGill University Health Centre; Montreal Neurological Institute and HospitalMontrealQCCanada
| | - Linda Papa
- Department of Emergency MedicineOrlando HealthOrlandoFLUSA
| | - Kenton Gregory
- Center for Regenerative MedicineOregon Health and Science UniversityPortlandORUSA
| | - Robert L. Folmer
- Department of OtolaryngologyOregon Health and Science UniversityPortlandORUSA
- National Center for Rehabilitative Auditory ResearchVA Portland Health Care SystemPortlandORUSA
| | - William C. Walker
- Department of Physical Medicine and RehabilitationVirginia Commonwealth UniversityRichmondVAUSA
| | - Vivek Prabhakaran
- Department of Radiology, University of Wisconsin Hospitals and ClinicsUniversity of WisconsinMadisonWIUSA
| | | | | | - Michael Yochelson
- Shepherd CenterAtlantaGAUSA
- MedStar National Rehabilitation NetworkWashingtonDCUSA
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26
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Petrosino NJ, Cosmo C, Berlow YA, Zandvakili A, van ’t Wout-Frank M, Philip NS. Transcranial magnetic stimulation for post-traumatic stress disorder. Ther Adv Psychopharmacol 2021; 11:20451253211049921. [PMID: 34733479 PMCID: PMC8558793 DOI: 10.1177/20451253211049921] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 09/09/2021] [Indexed: 01/14/2023] Open
Abstract
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. While current treatment options are effective for some, many individuals fail to respond to first-line psychotherapies and pharmacotherapy. Transcranial magnetic stimulation (TMS) has emerged over the past several decades as a noninvasive neuromodulatory intervention for psychiatric disorders including depression, with mounting evidence for its safety, tolerability, and efficacy in treating PTSD. While several meta-analyses of TMS for PTSD have been published to date showing large effect sizes on PTSD overall, there is marked variability between studies, making it difficult to draw simple conclusions about how best to treat patients. The following review summarizes over 20 years of the existing literature on TMS as a PTSD treatment, and includes nine randomized controlled trials and many other prospective studies of TMS monotherapy, as well as five randomized controlled trials investigating TMS combined with psychotherapy. While the majority of studies utilize repetitive TMS targeted to the right dorsolateral prefrontal cortex (DLPFC) at low frequency (1 Hz) or high frequency (10 or 20 Hz), others have used alternative frequencies, targeted other regions (most commonly the left DLPFC), or trialed different stimulation protocols utilizing newer TMS modalities such as synchronized TMS and theta-burst TMS (TBS). Although it is encouraging that positive outcomes have been shown, there is a paucity of studies directly comparing available approaches. Biomarkers, such as functional imaging and electroencephalography, were seldomly incorporated yet remain crucial for advancing our knowledge of how to predict and monitor treatment response and for understanding mechanism of action of TMS in this population. Effects on PTSD are often sustained for up to 2-3 months, but more long-term studies are needed in order to understand and predict duration of response. In short, while TMS appears safe and effective for PTSD, important steps are needed to operationalize optimal approaches for patients suffering from this disorder.
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Affiliation(s)
- Nicholas J. Petrosino
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Camila Cosmo
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Yosef A. Berlow
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Amin Zandvakili
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Mascha van ’t Wout-Frank
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, RI, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Noah S. Philip
- VA RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, 830 Chalkstone Avenue, Providence, RI 02908, USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
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Cheng P, Zhou Y, Xu LZ, Chen YF, Hu RL, Zou YL, Li ZX, Zhang L, Shun Q, Yu X, Li LJ, Li WH. Clinical application of repetitive transcranial magnetic stimulation for post-traumatic stress disorder: A literature review. World J Clin Cases 2021; 9:8658-8665. [PMID: 34734044 PMCID: PMC8546820 DOI: 10.12998/wjcc.v9.i29.8658] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/30/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
The efficacy of traditional treatment for post-traumatic stress disorder (PTSD) is still unsatisfactory. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in the treatment of various types of mental disorders, including PTSD. Although rTMS has been demonstrated to be effective in many cases, there are still arguments regarding its mechanism and protocol. This review aims to summarize the origin, development, principle, and future direction of rTMS and introduce this neuro-stimulation therapy to relevant clinicians.
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Affiliation(s)
- Peng Cheng
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ying Zhou
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Li-Zhi Xu
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ya-Fei Chen
- Xiangya Medical School, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Ruo-Lin Hu
- Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Yi-Ling Zou
- Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Ze-Xuan Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Li Zhang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Qi Shun
- Research Center for Brain Science and Human-like Intelligence, Xi’an Jiaotong University, Xi’an 710049, Shannxi Province, China
| | - Xun Yu
- Product Department, Solide Brain Medical Technology, Ltd., Xi’an 710043, Shannxi Province, China
| | - Ling-Jiang Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
| | - Wei-Hui Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
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Phillips A, Sami S, Adamson M. Sex Differences in Neuromodulation Treatment Approaches for Traumatic Brain Injury: A Scoping Review. J Head Trauma Rehabil 2021; 35:412-429. [PMID: 33165154 DOI: 10.1097/htr.0000000000000631] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Neuromodulatory brain stimulation interventions for traumatic brain injury (TBI)-related health sequelae, such as psychiatric, cognitive, and pain disorders, are on the rise. Because of disproportionate recruitment and epidemiological reporting of TBI-related research in men, there is limited understanding of TBI development, pathophysiology, and treatment intervention outcomes in women. With data suggesting sex-related variances in treatment outcomes, it is important that these gaps are addressed in emerging, neuromodulatory treatment approaches for TBI populations. METHODS Four research databases (PubMED, EMBASE, CINAHL, and PsycINFO) were electronically searched in February 2020. DESIGN This PRISMA Scoping Review (PRISMA-ScR)-guided report contextualizes the importance of reporting sex differences in TBI + neuromodulatory intervention studies and summarizes the current state of reporting sex differences when investigating 3 emerging interventions for TBI outcomes. RESULTS Fifty-four studies were identified for the final review including 12 controlled trials, 16 single or case series reports, and 26 empirical studies. Across all studies reviewed, 68% of participants were male, and only 7 studies reported sex differences as a part of their methodological approach, analysis, or discussion. CONCLUSION This review is hoped to update the TBI community on the current state of evidence in reporting sex differences across these 3 neuromodulatory treatments of post-TBI sequelae. The proposed recommendations aim to improve future research and clinical treatment of all individuals suffering from post-TBI sequelae.
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Affiliation(s)
- Angela Phillips
- Department of Rehabilitation, Veterans Affairs Palo Alto Health Care System, Palo Alto, California (Drs Phillips and Adamson and Mr Sami); and Departments of Psychiatry & Behavioral Sciences (Dr Phillips) and Neurosurgery (Dr Adamson), Stanford School of Medicine, Stanford, California
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29
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McGirr A, Devoe DJ, Raedler A, Debert CT, Ismail Z, Berlim MT. Repetitive Transcranial Magnetic Stimulation for the Treatment of Post-traumatic Stress Disorder: A Systematic Review and Network Meta-analysis: La Stimulation Magnétique Transcrânienne Répétitive Pour le Traitement du Trouble de Stress Post-Traumatique : Une Revue Systématique et une Méta-Analyse en Réseau. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2021; 66:763-773. [PMID: 33355483 PMCID: PMC8504289 DOI: 10.1177/0706743720982432] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment modality for Post-traumatic stress disorder (PTSD). Several targets and stimulation parameters have been investigated, and while previous meta-analyses have suggested that rTMS is efficacious, these have pooled different stimulation parameters and targets, and the relative efficacy of each is unknown. METHODS We therefore performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) by searching MEDLINE, EMBASE, CENTRAL, and PsycINFO and retaining RCTs with at least 5 individuals per arm and clinician-rated PTSD symptoms (PROSPERO CRD42019134984). We adhered to PRISMA guidelines, and 2 independent reviewers screened studies for eligibility and extracted the primary outcome of clinician-rated PTSD symptoms. Dropouts were extracted as a proxy for acceptability. Random effects pairwise meta-analyses and a network meta-analysis were performed. RESULTS We synthesize data from 10 RCTs with a total of 421 participants. Two rTMS interventions targeting the right dorsolateral prefrontal cortex (DLPFC) improved PTSD symptoms relative to sham: low-frequency stimulation (SMD = 0.70; 95% CI, 0.22 to 1.18) and high-frequency stimulation (SMD = 0.71; 95% CI, 0.11 to 1.31). Medial PFC dTMS, right DLPFC intermittent theta-burst stimulation, and left DLPFC high-frequency stimulation did not separate from sham. Dropouts as a proxy for acceptability revealed no differences between any of the active conditions or sham nor did any of the active conditions differ from each other. CONCLUSION The current literature does not support efficacy differences between interventions; however, protocols stimulating the right DLPFC appear superior to sham. It is unclear whether this reflects heterogeneity in pathology requiring a personalized medicine approach or nonspecific mechanisms of rTMS.
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Affiliation(s)
- Alexander McGirr
- Department of Psychiatry, 70401University of Calgary, Alberta, Canada.,Hotchkiss Brain Institute, 70401University of Calgary, Alberta, Canada.,Mathison Centre for Mental Health Research and Education, Calgary, Alberta, Canada
| | - Daniel J Devoe
- Department of Psychiatry, 70401University of Calgary, Alberta, Canada.,Hotchkiss Brain Institute, 70401University of Calgary, Alberta, Canada.,Mathison Centre for Mental Health Research and Education, Calgary, Alberta, Canada
| | - Amelie Raedler
- Department of Psychiatry, 70401University of Calgary, Alberta, Canada.,Hotchkiss Brain Institute, 70401University of Calgary, Alberta, Canada.,Mathison Centre for Mental Health Research and Education, Calgary, Alberta, Canada
| | - Chantel T Debert
- Hotchkiss Brain Institute, 70401University of Calgary, Alberta, Canada.,Department of Clinical Neuroscience, 70401University of Calgary, Alberta, Canada
| | - Zahinoor Ismail
- Department of Psychiatry, 70401University of Calgary, Alberta, Canada.,Hotchkiss Brain Institute, 70401University of Calgary, Alberta, Canada.,Mathison Centre for Mental Health Research and Education, Calgary, Alberta, Canada.,Department of Clinical Neuroscience, 70401University of Calgary, Alberta, Canada
| | - Marcelo T Berlim
- Department of Psychiatry, 5620McGill University, Montreal, Quebec, Canada.,Douglas Mental Health University Institute, Montreal, Quebec, Canada
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Harris A, Reece J. Transcranial magnetic stimulation as a treatment for posttraumatic stress disorder: A meta-analysis. J Affect Disord 2021; 289:55-65. [PMID: 33940319 DOI: 10.1016/j.jad.2021.04.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/27/2021] [Accepted: 04/02/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Posttraumatic stress disorder (PTSD) is a pervasive mental health condition with limited treatment success. Transcranial magnetic stimulation (TMS) has shown positive outcomes for people with PTSD, using different treatment protocols. This meta-analysis sought to examine which variables in TMS treatment are associated with treatment benefits. METHODS A literature search of major online research databases from inception to September 15, 2020 was conducted to identify primary research studies using TMS to treat PTSD. Treatment effect data and TMS treatment variables were coded and analysed using a random effects model. Meta-regression and analyses of moderating variables were conducted to ascertain which variables were associated with significant treatment effects. RESULTS An overall effect size of d = 1.17, 95% CI [0.89 - 1.45] for TMS as a treatment for PTSD was found. Analysis of moderators showed that there was a significantly larger treatment effect for high frequency TMS (d = 1.44) compared with low frequency (d = 0.72), p = .006; there was no significant difference between TMS targeting the left dorsolateral prefrontal cortex (DLPFC) and the right DLPFC; and larger treatment doses were not associated with stronger treatment effects. LIMITATIONS Not all published studies were available in English or reported the necessary data to be included in this meta-analysis. CONCLUSIONS TMS shows potential as a treatment for PTSD, although further research is required to understand the neurological mechanisms of TMS on specific PTSD symptoms so that more effective treatment can be designed for individuals.
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Affiliation(s)
- Adam Harris
- School of Psychological Sciences, Australian College of Applied Psychology, Sydney, Australia; Australian Defence Force, Joint Health Unit - Central Australia.
| | - John Reece
- School of Psychological Sciences, Australian College of Applied Psychology, Melbourne, Australia
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Smits FM, Schutter DJLG, van Honk J, Geuze E. Does non-invasive brain stimulation modulate emotional stress reactivity? Soc Cogn Affect Neurosci 2021; 15:23-51. [PMID: 31993648 PMCID: PMC7171378 DOI: 10.1093/scan/nsaa011] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 12/09/2019] [Accepted: 01/08/2020] [Indexed: 12/14/2022] Open
Abstract
Excessive emotional responses to stressful events can detrimentally affect psychological functioning and mental health. Recent studies have provided evidence that non-invasive brain stimulation (NBS) targeting the prefrontal cortex (PFC) can affect the regulation of stress-related emotional responses. However, the reliability and effect sizes have not been systematically analyzed. In the present study, we reviewed and meta-analyzed the effects of repetitive transcranial magnetic (rTMS) and transcranial direct current stimulation (tDCS) over the PFC on acute emotional stress reactivity in healthy individuals. Forty sham-controlled single-session rTMS and tDCS studies were included. Separate random effects models were performed to estimate the mean effect sizes of emotional reactivity. Twelve rTMS studies together showed no evidence that rTMS over the PFC influenced emotional reactivity. Twenty-six anodal tDCS studies yielded a weak beneficial effect on stress-related emotional reactivity (Hedges’ g = −0.16, CI95% = [−0.33, 0.00]). These findings suggest that a single session of NBS is insufficient to induce reliable, clinically significant effects but also provide preliminary evidence that specific NBS methods can affect emotional reactivity. This may motivate further research into augmenting the efficacy of NBS protocols on stress-related processes.
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Affiliation(s)
- Fenne M Smits
- Brain Research & Innovation Centre, Ministry of Defence, Lundlaan 1, 3584 EZ, Utrecht, The Netherlands.,Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Dennis J L G Schutter
- Experimental Psychology, Helmholtz Institute, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, The Netherlands
| | - Jack van Honk
- Experimental Psychology, Helmholtz Institute, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, The Netherlands.,Department of Psychiatry and Mental Health, University of Cape Town, Observatory, 7925, Cape Town, South Africa.,Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925, Cape Town, South Africa
| | - Elbert Geuze
- Brain Research & Innovation Centre, Ministry of Defence, Lundlaan 1, 3584 EZ, Utrecht, The Netherlands.,Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
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High frequency repetitive Transcranial Magnetic Stimulation promotes long lasting phrenic motoneuron excitability via GABAergic networks. Respir Physiol Neurobiol 2021; 292:103704. [PMID: 34058433 DOI: 10.1016/j.resp.2021.103704] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 05/17/2021] [Accepted: 05/25/2021] [Indexed: 11/21/2022]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a promising, innovative, and non-invasive therapy used clinically. Efficacy of rTMS has been demonstrated to ameliorate psychiatric disorders and neuropathic pain through neuromodulation of affected neural circuits. However, little is known about the mechanisms and the specific neural circuits via which rTMS facilitates these functional effects. The aim of this study was to begin revealing the mechanisms by which rTMS may tap into existing neural circuits, by using a well characterized spinal motor circuit - the phrenic circuit. Here we hypothesized that rTMS can be used to enhance phrenic motoneuron excitability in anesthetized Sprague Dawley rats. Multiple acute rTMS protocols were used revealing 10 Hz rTMS protocol induced a robust, long-lasting increase in phrenic motoneuron excitability, functionally evaluated by diaphragm motor evoked potentials (59.1 ± 21.1 % of increase compared to baseline 60 min after 10 Hz protocol against 6.0 ± 5.8 % (p = 0.007) for Time Control, -5.8 ± 7.4 % (p < 0.001) for 3 Hz, and 5.2 ± 12.5 % (p = 0.008) for 30 Hz protocols). A deeper analyze allowed to discriminate "responder" and "non-responder" subgroups among 10 Hz rTMS treated animals. Intravenous injections of GABAA and GABAB receptor agonists prior to 10 Hz rTMS treatment, abolished the enhanced phrenic motoneuron excitability, suggesting GABAergic input plays a mechanistic role in rTMS-induced phrenic excitability. These data demonstrate that a single high frequency rTMS protocol at 10 Hz increases phrenic motoneuron excitability, mediated by a local GABAergic "disinhibition". By understanding how rTMS can be used to affect neural circuits non-invasively we can begin to harness the therapeutic potential of this neuromodulatory strategy to promote recovery after disease or injury to the central nervous system.
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Belsher BE, Beech EH, Reddy MK, Smolenski DJ, Rauch SAM, Kelber M, Issa F, Lewis C, Bisson JI. Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: A systematic review. J Psychiatr Res 2021; 138:598-606. [PMID: 33992983 DOI: 10.1016/j.jpsychires.2021.05.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/01/2021] [Accepted: 05/01/2021] [Indexed: 01/18/2023]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) as a treatment for posttraumatic stress disorder (PTSD) has gained interest over the past two decades. However, it has yet to be recommended in major treatment guidelines. We conducted a systematic review of randomized controlled trials to examine the efficacy of rTMS for PTSD. Thirteen studies with 549 participants were included in this review. We compared the effects of (1) rTMS versus sham, and (2) high-frequency (HF) versus low-frequency (LF) rTMS, on posttreatment PTSD scores and other secondary outcomes. We calculated the standardized mean differences (SMD) to determine the direction of effects, and unstandardized mean differences to estimate the magnitude of efficacy. At post-treatment, rTMS was superior to sham comparison in reducing PTSD (SMD = -1.13, 95% CI: -2.10 to -0.15) and depression severity (SMD = -0.83, 95% CI: -1.30 to -0.36). The quality of evidence, however, was rated very low due to small samples sizes, treatment heterogeneity, inconsistent results, and an imprecise pooled effect. HF rTMS was associated with slightly improved, albeit imprecise, outcomes compared to LF rTMS on PTSD (SMD = -0.19, 95% CI: -1.39 to 1.00) and depression (SMD = -1.09, 95% CI: -1.65 to -0.52) severity. Further research is required to advance the evidence on this treatment.
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Affiliation(s)
- Bradley E Belsher
- Carl T Hayden Veterans Medical Center, 650 E Indian School Rd, Phoenix, AZ, 85012, USA; Uniformed Services University of the Health Sciences, 4310 Jones Bridge Road, Bethesda, MD, 20814, USA.
| | - Erin H Beech
- Psychological Health Center of Excellence, Defense Health Agency, 1335 East West Highway, Silver Spring, MD, 20910, USA
| | - Madhavi K Reddy
- Psychological Health Center of Excellence, Defense Health Agency, 1335 East West Highway, Silver Spring, MD, 20910, USA
| | - Derek J Smolenski
- Psychological Health Center of Excellence, Defense Health Agency, 1335 East West Highway, Silver Spring, MD, 20910, USA
| | - Sheila A M Rauch
- Atlanta VA Healthcare System, 1670 Clairmont Road, Decatur, GA, 300233, USA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park, 3rd Floor, Atlanta, GA, 30329, USA
| | - Marija Kelber
- Psychological Health Center of Excellence, Defense Health Agency, 1335 East West Highway, Silver Spring, MD, 20910, USA
| | - Fuad Issa
- Psychological Health Center of Excellence, Defense Health Agency, 1335 East West Highway, Silver Spring, MD, 20910, USA
| | - Catrin Lewis
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK
| | - Jonathan I Bisson
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK
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Yasinski C, Maples-Keller J, Trautner H, Job G, Rauch SAM, McDonald WM, Rothbaum BO. A Review of PTSD Augmentation Strategies for Older Adults and Case of rTMS-Augmented Prolonged Exposure. Am J Geriatr Psychiatry 2020; 28:1317-1327. [PMID: 32718854 DOI: 10.1016/j.jagp.2020.06.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/11/2020] [Accepted: 06/17/2020] [Indexed: 10/24/2022]
Abstract
Evidence-based psychotherapies such as prolonged exposure therapy (PE) are recommended by clinical practice guidelines as first-line treatments for post-traumatic stress disorder (PTSD) and are safe and acceptable for use with older adults. One third to one half of all patients do not achieve a clinically meaningful response to standard outpatient PE and recent research suggests that older adults in particular may experience barriers to full engagement and response. Standard treatment may be challenging in older adults due to cognitive, medical, and psychosocial barriers. This article reviews the current state of the evidence on adjunctive and second-tier interventions that show promise for increasing response and/or engagement in evidence-based psychotherapy for PTSD, including medications such as d-cycloserine and 3,4-methylenedioxy-methamphetamine, neuromodulation techniques such as repetitive transcranial magnetic stimulation, and augmentations to the structure and content of psychotherapy, such as intensive outpatient formats. A case illustration of successful application of multiple augmentations to PE with an initially nonresponsive older adult patient is presented. A creative interdisciplinary approach based in available research may be beneficial for older adults who do not respond to first-line treatments.
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Affiliation(s)
- Carly Yasinski
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA.
| | - Jessica Maples-Keller
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA
| | - Hannah Trautner
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA
| | - Gregory Job
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA
| | - Sheila A M Rauch
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA
| | - William M McDonald
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA
| | - Barbara O Rothbaum
- Department of Psychiatry and Behavioral Sciences (CY, JMK, HT, GJ, SAMR, WMMD, BOR), Emory University School of Medicine, Atlanta, GA
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Leong K, Chan P, Ong L, Zwicker A, Willan S, Lam RW, McGirr A. A Randomized Sham-controlled Trial of 1-Hz and 10-Hz Repetitive Transcranial Magnetic Stimulation (rTMS) of the Right Dorsolateral Prefrontal Cortex in Civilian Post-traumatic Stress Disorder: Un essai randomisé contrôlé simulé de stimulation magnétique transcrânienne repetitive (SMTr) de 1 Hz et 10 Hz du cortex préfrontal dorsolatéral droit dans le trouble de stress post-traumatique chez des civils. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2020; 65:770-778. [PMID: 32379487 PMCID: PMC7564694 DOI: 10.1177/0706743720923064] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Despite effective psychological and pharmacological treatments, there is a large unmet burden of illness in post-traumatic stress disorder (PTSD). Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention and a putative treatment strategy for PTSD. The evidence base to date suggests that rTMS targeting the dorsolateral prefrontal cortex (DLPFC), in particular the right DLPFC, leads to improvements in PTSD symptoms. However, optimal stimulation parameters have yet to be determined. In this study, we examine the efficacy of high- and low-frequency rTMS of the right DLPFC using a randomized, double-blind, sham-controlled design in civilian PTSD. METHODS We conducted a 2-week single-site randomized sham-controlled trial of rTMS targeting the right DLPFC. We recruited civilians aged 19 to 70 with PTSD and randomized subjects with allocation concealment to daily 1-Hz rTMS, 10-Hz rTMS, or sham rTMS. The primary outcome was improvement in Clinician Administered PTSD Scale-IV (CAPS-IV). Secondary outcomes included change in depressive and anxiety symptoms. RESULTS We recruited 31 civilians with PTSD. One 1-Hz-treated patient developed transient suicidal ideation. Analyses revealed significant improvement in CAPS-IV symptoms in the 1-Hz group relative to sham (Hedges' g = -1.07) but not in the 10-Hz group. This was not attributable to changes in anxious or depressive symptomatology. Ten-Hz stimulation appeared to improve depressive symptoms compared to sham. CONCLUSION Low-frequency rTMS is efficacious in the treatment of civilian PTSD. Our data suggest that high-frequency rTMS of the right DLPFC is worthy of additional investigation for the treatment of depressive symptoms comorbid with PTSD.
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Affiliation(s)
- Kawai Leong
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada
| | - Peter Chan
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada.,8166Brainstim Healthcare, Vancouver, British Columbia, Canada
| | - Larry Ong
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada
| | - Amy Zwicker
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.,380154Vancouver General Hospital, British Columbia, Canada
| | - Sharon Willan
- 380154Vancouver General Hospital, British Columbia, Canada
| | - Raymond W Lam
- Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada
| | - Alexander McGirr
- Department of Psychiatry, 2129University of Calgary, Alberta, Canada.,Hotchkiss Brain Institute, 2129University of Calgary, Alberta, Canada.,Mathison Centre for Mental Health Research and Education, Calgary, Alberta, Canada
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36
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Hwang JH, Hwang H, Kim HR, Hong JS, Han DH, Shin JH, Kim SH, Kim SM. Effects of Repetitive Transcranial Magnetic Stimulation on Improvement of Mental Health and Clinical Parameters in Depressed Hemodialysis Patients: a Pilot Study. J Korean Med Sci 2020; 35:e205. [PMID: 32627438 PMCID: PMC7338214 DOI: 10.3346/jkms.2020.35.e205] [Citation(s) in RCA: 0] [Impact Index Per Article: 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: 01/13/2020] [Accepted: 05/14/2020] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND This study aimed to evaluate the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) as a nonpharmacologic treatment in depressed hemodialysis patients. METHODS Patients who scored ≥ 5 on the Patient Health Questionnaire-9 were randomized to either the rTMS (n = 7) or sham group (n = 7). The rTMS group was stimulated with a 110% motor threshold and 10 Hz on the left dorsolateral prefrontal cortex for 20 minutes, three times a week, for 4 weeks. In the sham group, the "1-wing 90-degree method" was used. We analyzed clinical indices before and after the intervention, as well as data from quantitative electroencephalography (frontal alpha asymmetry [FAA]), and various psychiatric questionnaires (Beck Depression Inventory-II, Beck Anxiety Inventory [BAI], Symptom Checklist-90-Revised Somatization Subscale [SCL-90R-SOM]), and Perceived Stress Scale. RESULTS One month after rTMS, the changes in hemoglobin A1c levels in the rTMS group were significantly greater than those in the sham group (F = 6.687, P = 0.032). The changes in BAI scores in the rTMS group were significantly greater than those in the sham group (F = 6.700, P = 0.025), and the changes in SCL-90R-SOM scores in the rTMS group were greater than those in the sham group (F = 4.943, P = 0.048). In addition, the changes in the FAA value at the F7 and F8 electrodes in the rTMS group were greater than those in the sham group (F = 6.468, P = 0.027). CONCLUSION In depressed hemodialysis patients, rTMS may improve anxiety and somatization symptoms, which may lead to improvements in clinical measures. Trial Registration Clinical Research Information Service Identifier: KCT0004082.
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Affiliation(s)
- Jin Ho Hwang
- Division of Nephrology, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Hyunchan Hwang
- Department of Psychiatry, Chung-Ang University Hospital, Seoul, Korea
| | - Hye Ri Kim
- Department of Psychiatry, Chung-Ang University Hospital, Seoul, Korea
| | - Ji Sun Hong
- Department of Psychiatry, Chung-Ang University Hospital, Seoul, Korea
| | - Doug Hyun Han
- Department of Psychiatry, Chung-Ang University Hospital, Seoul, Korea
| | - Jung Ho Shin
- Division of Nephrology, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Su Hyun Kim
- Division of Nephrology, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Sun Mi Kim
- Department of Psychiatry, Chung-Ang University Hospital, Seoul, Korea.
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Gervasio M, Beatty A, Kavanaugh B, Cancilliere MK, Holler K. The association between neurocognition and sexual abuse within a children's psychiatric inpatient program. Clin Neuropsychol 2020; 36:189-206. [PMID: 32613898 DOI: 10.1080/13854046.2020.1781932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Objective: The aim of this study was to understand the detrimental effects of sexual abuse on neuropsychological variables including child's intelligence, executive functioning (EF), and learning/memory within a pediatric inpatient population.Method: This study examined the effect of sexual abuse on children's intelligence, EF, and learning/memory by conducting a retrospective chart review for 144 children (aged 7-12) who completed a neuropsychological assessment during a psychiatric inpatient hospitalization. Of the 144 children, participants were matched two to one by gender and age, with one group (n = 52) categorized by reported sexual abuse and the other group (n = 92) categorized by no reported sexual abuse. The neuropsychological measures included the Wechsler Abbreviated Scale of Intelligence (WASI-I/II) or Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), Wide Range Assessment of Memory and Learning - Second Edition (WRAML-2): Story Memory Immediate/Delayed Recall and Delayed Recognition, Trail Making Test-B, Stroop Interference Test: Color-Word Condition, WRAML-2: Sentence Memory and Conners Continuous Performance Test-Second Edition.Results: Statistical analysis showed that participants with reported sexual abuse had significantly (p< .05) lower intelligence, EF, and learning/memory skills than those without reported sexual abuse. Only working memory and cognitive flexibility differences remained after controlling for clinical variables (e.g., PTSD, amount of total abuse types).Conclusions: These findings contributed to the limited research on the detrimental effects of sexual abuse in a pediatric inpatient population. They demonstrated a relationship between early sexual abuse and neuropsychological deficits, specifically executive function and IQ deficits.
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Affiliation(s)
- Maddi Gervasio
- Department of Psychiatry & Human Behavior, E. P. Bradley Hospital, East Providence, RI, USA
| | - Avery Beatty
- Department of Human Development and Family Studies, University of Rhode Island, Kingston, RI, USA
| | - Brian Kavanaugh
- Department of Psychiatry & Human Behavior, E. P. Bradley Hospital, East Providence, RI, USA.,Department of Psychiatry & Human Behavior, Alpert Medical School of Brown University, East Providence, RI, USA
| | | | - Karen Holler
- Department of Psychiatry & Human Behavior, E. P. Bradley Hospital, East Providence, RI, USA.,Department of Psychiatry & Human Behavior, Alpert Medical School of Brown University, East Providence, RI, USA
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Effects of repetitive transcranial magnetic stimulation in subjects with sleep disorders. Sleep Med 2020; 71:113-121. [PMID: 32173186 DOI: 10.1016/j.sleep.2020.01.028] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 01/06/2020] [Accepted: 01/31/2020] [Indexed: 01/08/2023]
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Fonzo GA, Federchenco V, Lara A. Predicting and Managing Treatment Non-Response in Posttraumatic Stress Disorder. CURRENT TREATMENT OPTIONS IN PSYCHIATRY 2020; 7:70-87. [PMID: 33344106 PMCID: PMC7748158 DOI: 10.1007/s40501-020-00203-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW This review aims to synthesize existing research regarding the definition of treatment resistance in posttraumatic stress disorder (PTSD), predictors of treatment non-response to first-line interventions, and emerging second-line PTSD treatment options into an accessible resource for the practicing clinician. RECENT FINDINGS The concept of treatment resistance in PTSD is currently poorly defined and operationalized. There are no well-established predictors of treatment non-response utilized in routine clinical care, but existing research identifies several potential candidate markers, including male gender, low social support, chronic and early life trauma exposure, comorbid psychiatric disorders, severe PTSD symptoms, and poor physical health. The most promising available treatment options for PTSD patients non-responsive to first-line psychotherapies and antidepressants include transcranial magnetic stimulation and ketamine infusion. Methylenedioxymethamphetamine-assisted psychotherapy also appears promising but is only available in a research context. These options require careful consideration of risks and benefits for a particular patient. SUMMARY More research is required to develop a robust, clinically-useful definition of treatment resistance in PTSD; identify reliable, readily assessable, and generalizable predictors of PTSD treatment non-response; and implement measurement and prediction in clinical settings to identify individuals unlikely to respond to first-line treatments and direct them to appropriate second-line treatments.
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Affiliation(s)
- Gregory A. Fonzo
- Department of Psychiatry, Dell Medical School, The University of Texas at Austin
| | - Vecheslav Federchenco
- General Psychiatry Residency, Dell Medical School, The University of Texas at Austin
- Equal contributions to authorship
| | - Alba Lara
- General Psychiatry Residency, Dell Medical School, The University of Texas at Austin
- Equal contributions to authorship
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40
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Kan RLD, Zhang BBB, Zhang JJQ, Kranz GS. Non-invasive brain stimulation for posttraumatic stress disorder: a systematic review and meta-analysis. Transl Psychiatry 2020; 10:168. [PMID: 32467579 PMCID: PMC7256039 DOI: 10.1038/s41398-020-0851-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 05/05/2020] [Accepted: 05/14/2020] [Indexed: 12/11/2022] Open
Abstract
Approximately 7-9% of people develop posttraumatic stress disorder in their lifetime, but standard pharmacological treatment or psychotherapy shows a considerable individual variation in their effectiveness. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) hold promise for the treatment of posttraumatic stress disorder. The objective of this meta-analysis was to summarize the existing evidence on the therapeutic effects of these brain stimulation treatments on posttraumatic core symptoms. We systematically retrieved articles published between 1st January 2000 and 1st January 2020 comparing the effects of active with sham stimulation or no intervention in posttraumatic patients from eight databases. Random-effects model was used for meta-analysis. Meta-regression and subgroup meta-analysis was performed to investigate the influence of stimulation dose and different stimulation protocols, respectively. 20 studies were included in this review, where of 11 randomized controlled trials were subjected to quantitative analysis. Active stimulation demonstrated significant reductions of core posttraumatic symptoms with a large effect size (Hedge's g = -0.975). Subgroup analysis showed that both excitatory and inhibitory rTMS of the right dorsolateral prefrontal cortex led to symptom reductions with a large (Hedges' g = -1.161, 95% CI, -1.823 to -0.499; p = 0.015) and medium effect size (Hedges' g = -0.680, 95% CI: -0.139 to -0.322; p ≤ 0.001) respectively. Results further indicated significant durability of symptom-reducing effects of treatments during a two to four weeks period post stimulation (Hedges' g = -0.909, 95% CI: -1.611 to -0.207; p = 0.011). rTMS of the right dorsolateral prefrontal cortex appears to have a positive effect in reducing core symptoms in patients with posttraumatic stress disorder.
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Affiliation(s)
- Rebecca L D Kan
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR, China
| | - Bella B B Zhang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR, China
| | - Jack J Q Zhang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR, China
| | - Georg S Kranz
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR, China.
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
- The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, SAR, China.
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41
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Double Trouble: Treatment Considerations for Patients with Comorbid PTSD and Depression. ACTA ACUST UNITED AC 2020. [DOI: 10.1007/s40501-020-00213-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Kumar N, Vishnubhatla S, Wadhawan AN, Minhas S, Gupta P. A randomized, double blind, sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia. Brain Stimul 2020; 13:840-849. [DOI: 10.1016/j.brs.2020.02.016] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 02/13/2020] [Accepted: 02/17/2020] [Indexed: 12/15/2022] Open
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Repetitive transcranial magnetic stimulation targeting the insular cortex for reduction of heavy drinking in treatment-seeking alcohol-dependent subjects: a randomized controlled trial. Neuropsychopharmacology 2020; 45:842-850. [PMID: 31711065 PMCID: PMC7075882 DOI: 10.1038/s41386-019-0565-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 10/08/2019] [Accepted: 11/01/2019] [Indexed: 11/08/2022]
Abstract
Insula responses to drug cues are correlated with cravings, and lesions in this area reduce nicotine seeking. Here, we investigated the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) targeting the insula in alcohol addiction. Treatment-seeking alcohol-dependent patients (Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition; N = 56) participated in this double-blind, sham-controlled, randomized trial. Participants received 10 Hz rTMS or sham using an H8 coil, 5 days a week for 3 weeks. Stimulation targeted insular cortex and overlaying regions bilaterally, while excluding anterior prefrontal areas. Craving and self-reported as well as biomarker-based drinking measures were collected at baseline, during treatment, and through 12 weeks. Resting-state magnetic resonance imaging (rsMRI) data were collected before and after treatment. Task-based MRI was used to probe brain correlates of reward processing, affective responses, and alcohol following completion of treatment. A marked overall decrease in craving and drinking measures was observed during treatment, but did not differ between rTMS or sham stimulation. Both groups equally increased their alcohol use following completion of treatment and through the 12-week follow-up. Analysis using seeds in the insula identified differences in resting-state connectivity between active and sham groups at completion of treatment, potentially indicating an ability of treatment to modify insula function. However, while each task robustly replicated brain responses established in the literature, no effects of rTMS were found. Collectively, this study does not support efficacy of rTMS targeting the insula in alcohol addiction.
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Ahmadizadeh MJ, Rezaei M, Fitzgerald PB. Transcranial direct current stimulation (tDCS) for post-traumatic stress disorder (PTSD): A randomized, double-blinded, controlled trial. Brain Res Bull 2019; 153:273-278. [DOI: 10.1016/j.brainresbull.2019.09.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 09/19/2019] [Indexed: 12/12/2022]
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Abstract
PURPOSE OF REVIEW Childhood maltreatment is associated with all types of eating disorders. We provide a systematic review of the recent literature on comorbid posttraumatic stress disorder (PTSD) in patients with eating disorders, and focus on prevalence, relationship with symptom severity, operating mechanisms and treatment. RECENT FINDINGS The prevalence of comorbid PTSD in patients with eating disorders ranges from 9 to 24%, with research suggesting that comorbid PTSD is associated with more severe eating disorder symptoms. Maladaptive emotional regulation strategies may mediate the relationship between PTSD and eating disorders. Two pilot studies provide preliminary evidence that concurrent cognitive behavior therapy (CBT) for PTSD and eating disorders may be beneficial and that repetitive transcranial magnetic stimulation (rTMS) could be helpful in the treatment of PTSD in some eating disorder patients. SUMMARY PTSD is a common comorbidity in patients with eating disorders and impacts the severity of their eating disorder symptoms. However, there is little research into concurrent treatments for PTSD and eating disorders. Difficulties in emotional regulation may be a common mechanism in both disorders.
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Koek RJ, Roach J, Athanasiou N, van 't Wout-Frank M, Philip NS. Neuromodulatory treatments for post-traumatic stress disorder (PTSD). Prog Neuropsychopharmacol Biol Psychiatry 2019; 92:148-160. [PMID: 30641094 DOI: 10.1016/j.pnpbp.2019.01.004] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 12/19/2018] [Accepted: 01/10/2019] [Indexed: 12/12/2022]
Abstract
Electroconvulsive therapy has been used successfully in some individuals with posttraumatic stress disorder (PTSD) whose symptoms have not improved with other treatments. But there are only a few reports. Meanwhile, an array of new neuromodulation strategies, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, trigeminal nerve stimulation, and deep brain stimulation have been developed and applied experimentally in the treatment of other psychiatric disorders. This article will review the clinical evidence and mechanistic basis for their use in PTSD.
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Affiliation(s)
- Ralph J Koek
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at Los Angeles, CA, USA; Sepulveda Ambulatory Care Center, Veterans Administration Greater Los Angeles Healthcare System, North Hills, CA, USA.
| | - Janine Roach
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at Los Angeles, CA, USA; Oliveview Medical Center, Sylmar, CA, USA
| | - Nicholas Athanasiou
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at Los Angeles, CA, USA; San Fernando Mental Health Center, Granada Hills, CA, USA
| | - Mascha van 't Wout-Frank
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| | - Noah S Philip
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA; VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI, USA
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Lawson McLean A. Publication trends in transcranial magnetic stimulation: a 30-year panorama. Brain Stimul 2019; 12:619-627. [DOI: 10.1016/j.brs.2019.01.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 01/02/2019] [Accepted: 01/07/2019] [Indexed: 01/11/2023] Open
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Kozel FA, Van Trees K, Larson V, Phillips S, Hashimie J, Gadbois B, Johnson S, Gallinati J, Barrett B, Toyinbo P, Weisman M, Centorino M, Gibson CA, Catalano G. One hertz versus ten hertz repetitive TMS treatment of PTSD: A randomized clinical trial. Psychiatry Res 2019; 273:153-162. [PMID: 30641346 DOI: 10.1016/j.psychres.2019.01.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 12/19/2018] [Accepted: 01/01/2019] [Indexed: 02/06/2023]
Abstract
The purpose of this trial was to test whether right prefrontal cortex 1 Hz versus 10 Hz rTMS provides a significantly greater improvement in PTSD symptoms and/or function. Veterans 18 to 50 years of age suffering from PTSD were randomized to right prefrontal 1 Hz rTMS [2400 pulses/session] versus right prefrontal 10 Hz rTMS [2400 pulses/session]. The treatments were performed 5 days a week for 6 weeks with a 3-week taper using the NeuroStar system. There were one month and three months post treatment follow-up evaluations. Forty-four participants were enrolled with 17 being randomized to 1 Hz rTMS and 18 to 10 Hz rTMS. Both groups had significant improvement in PTSD and depression scores from baseline to the end of acute treatment. The 10 Hz group but not the 1 Hz group demonstrated significant improvement in function. Although both groups demonstrated significant improvement in PTSD and depression symptoms, a significant advantage for either the 1 Hz or 10 Hz frequency group on any of the scales acquired was not demonstrated. Further work is required with larger samples sizes to test whether low or high frequency is superior or if individual differences would indicate the more effective frequency.
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Affiliation(s)
- F Andrew Kozel
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; HSR&D Center of Innovation on Disability and Rehabilitation Research (CINDRR), James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA.
| | - Kimberly Van Trees
- Nursing Services, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA
| | - Valerie Larson
- HSR&D Center of Innovation on Disability and Rehabilitation Research (CINDRR), James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA
| | - Sean Phillips
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
| | - Jaffrey Hashimie
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
| | - Brian Gadbois
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
| | - Suzanne Johnson
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA
| | - Jessica Gallinati
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA
| | - Blake Barrett
- HSR&D Center of Innovation on Disability and Rehabilitation Research (CINDRR), James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; VISN 8 Patient Safety Center of Inquiry, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA
| | - Peter Toyinbo
- HSR&D Center of Innovation on Disability and Rehabilitation Research (CINDRR), James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, USA
| | - Mark Weisman
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
| | - Michael Centorino
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
| | - Carri-Ann Gibson
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
| | - Glenn Catalano
- Mental Health and Behavioral Sciences, James A. Haley Veterans' Administration Hospital and Clinics, Tampa, FL, USA; Department of Psychiatry and Behavioral Sciences, University of South Florida, Tampa, FL, USA
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Lebois LAM, Seligowski AV, Wolff JD, Hill SB, Ressler KJ. Augmentation of Extinction and Inhibitory Learning in Anxiety and Trauma-Related Disorders. Annu Rev Clin Psychol 2019; 15:257-284. [PMID: 30698994 DOI: 10.1146/annurev-clinpsy-050718-095634] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Although the fear response is an adaptive response to threatening situations, a number of psychiatric disorders feature prominent fear-related symptoms caused, in part, by failures of extinction and inhibitory learning. The translational nature of fear conditioning paradigms has enabled us to develop a nuanced understanding of extinction and inhibitory learning based on the molecular substrates to systems neural circuitry and psychological mechanisms. This knowledge has facilitated the development of novel interventions that may augment extinction and inhibitory learning. These interventions include nonpharmacological techniques, such as behavioral methods to implement during psychotherapy, as well as device-based stimulation techniques that enhance or reduce activity in different regions of the brain. There is also emerging support for a number of psychopharmacological interventions that may augment extinction and inhibitory learning specifically if administered in conjunction with exposure-based psychotherapy. This growing body of research may offer promising novel techniques to address debilitating transdiagnostic fear-related symptoms.
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Affiliation(s)
- Lauren A M Lebois
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Antonia V Seligowski
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Jonathan D Wolff
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Sarah B Hill
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
| | - Kerry J Ressler
- Division of Depression and Anxiety Disorders, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA;
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Amidfar M, Ko YH, Kim YK. Neuromodulation and Cognitive Control of Emotion. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1192:545-564. [DOI: 10.1007/978-981-32-9721-0_27] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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