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1.
Geroscience ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35553346

RESUMO

Investigating effects of aging on neurophysiological mechanisms underlying working memory provides a better understanding of potential targets for brain intervention to prevent cognitive decline. Theta-gamma coupling (TGC) indexes the ability to order information processed during working memory tasks. Frontal theta event-related synchronization (ERS) and parietal alpha event-related desynchronization (ERD) index cognitive control and interference inhibition, respectively. Relative contributions of TGC, theta ERS, and alpha ERD in relation to stimulus presentation are not characterized. Further, differential effect of normal aging on pre- or post-stimulus processes is unknown. Electroencephalography was recorded in 66 younger and 41 older healthy participants while performing 3-back working memory task. We assessed relationships between 3-back task performance and each of post-stimulus TGC, pre-stimulus parietal alpha ERD, and pre-stimulus frontal theta ERS in each age group. While older adults performed worse on 3-back task than younger adults, TGC, alpha ERD, or theta ERS did not differ between the two groups. TGC was positively associated with 3-back performance in both age groups; pre-stimulus alpha ERD was associated with performance among younger adults; and pre-stimulus theta ERS was not associated with performance in either group. Our findings suggest that both pre-stimulus interference inhibition and post-stimulus ordering of information are important for working memory in younger adults. In contrast, performance in older adults appears to depend only on post-stimulus ordering of information. These specific contributions of neurophysiological resources may explain the poorer performance of older adults and suggest different targets to enhance working memory in age groups.

2.
Neurosci Biobehav Rev ; : 104690, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35569580

RESUMO

Cross-frequency coupling (CFC), an electrophysiologically derived measure of oscillatory coupling in the brain, is believed to play a critical role in neuronal computation, learning and communication. It has received much recent attention in the study of both health and disease. We searched for literature that studied CFC during resting state and task-related activities during electroencephalography and magnetoencephalography in psychiatric disorders. Thirty-eight studies were identified, which included attention-deficit hyperactivity disorder, Alzheimer's dementia, autism spectrum disorder, bipolar disorder, depression, obsessive compulsive disorder, social anxiety disorder and schizophrenia. The systematic review was registered with PROSPERO (ID#CRD42021224188). The current review indicates measurable differences exist between CFC in disease states vs. healthy controls. There was variance in CFC at different regions of the brain within the same psychiatric disorders, perhaps this could be explained by the mechanisms and functionality of CFC. There was heterogeneity in methodologies used, which may lead to spurious CFC analyses. Going forward, standardized methodologies need to be established and utilized in further research to understand the neuropathophysiology associated with psychiatric disorders.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35393165

RESUMO

OBJECTIVE: Nonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication nonadherence in difficult-to-treat late-life depression. METHODS: Secondary analysis of data from a clinical trial of antidepressant pharmacotherapy for Major Depressive Disorder in 468 adults aged 60+ years. All participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was assessed 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that may predict antidepressant nonadherence during early (weeks 1-6), late (weeks 7-12), and augmentation (weeks 13--24) treatment. RESULTS: Poor cognitive function and early response were predictive of early nonadherence. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment. CONCLUSION: Future studies should consider the role of early response and cognitive function to improve antidepressant adherence, particularly among older adults who live alone.

4.
Lancet Psychiatry ; 9(6): 435-446, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35487236

RESUMO

BACKGROUND: Previous studies examining the risk of suicide death after treatment with electroconvulsive therapy have been confounded and the resulting uncertainty around the risk-benefit profile of electroconvulsive therapy might contribute to its underuse. We aimed to compare the risk of death by suicide after psychiatric hospitalisation among individuals with depression who had been exposed to electroconvulsive therapy with those who had not. METHODS: This was a propensity score-weighted, retrospective cohort study using linked population-level administrative health data for adults with depression who had been admitted to a designated psychiatric bed in Ontario, Canada for more than 3 days between April 1, 2007 and Dec 31, 2017. Electroconvulsive therapy exposure was defined as one or more physician billing procedure codes during hospitalisation. The primary outcome was death by suicide identified using administrative health records within 365 days following discharge. We used cause-specific Cox proportional hazards model to estimate the cause-specific hazard ratio (csHR) for electroconvulsive therapy-exposed and electroconvulsive therapy-unexposed individuals. Secondary outcomes were non-suicide death and all-cause mortality. FINDINGS: In the analytic cohort, there were 67 327 psychiatric hospitalisation records (27 231 men and 40 096 women; mean age 45·1 years [SD 16·8; range 18-103]), of whom 4982 were exposed to electroconvulsive therapy and 62 345 were not exposed to electroconvulsive therapy. No ethnicity data were available. In propensity-score weighted analyses, electroconvulsive therapy was associated with a significantly reduced risk of suicide death (csHR 0·53 [95% CI 0·31-0·92]). Accounting for non-suicide death as a competing risk had no effect on the findings. Electroconvulsive therapy was also associated with a significantly reduced risk of all-cause mortality (0·75 [0·58-0·97]), but not non-suicide death (0·83 [0·61-1·12]). INTERPRETATION: Among individuals admitted to hospital with depression, electroconvulsive therapy is associated with a significantly reduced risk of death by suicide in the year after discharge. This study reinforces the importance of electroconvulsive therapy, particularly for people with severe depression. FUNDING: Norris Scholars Award, Department of Psychiatry, University of Toronto, and the Canadian Institutes for Health Research.

5.
Acta Psychiatr Scand ; 145(5): 529-538, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35188677

RESUMO

OBJECTIVE: To investigate the effect of 10 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) on suicidality in patients with treatment-resistant depression (TRD). METHODS: We used data from a three-site randomized clinical trial comparing 10 Hz rTMS and iTBS applied to the left dorsolateral prefrontal cortex (DLPFC) in patients with TRD. We compared the effect of 10Hz rTMS and iTBS on suicidality as measured by the suicide item of the Hamilton Depression Rating Scale 17-item (HDRS-17). RESULTS: Suicidality remitted in 71 (43.7%) participants randomized to 10Hz stimulation and 91 (49.1%) participants randomized to iTBS, without a significant difference between the proportions in the two groups (Χ2  = 0.674, df = 1, p = 0.4117). There was a significant correlation between change in suicidality and change in depression severity for both modalities (10 Hz, Pearson's r = 0.564; iTBS, Pearson's r = 0.502), with a significantly larger decrease in depression severity for those in whom suicidality remitted compared to those in whom it did not (t = 10.912, df = 276.8, p < 0.001). CONCLUSIONS: Both 10 Hz and iTBS rTMS were effective in reducing suicidality in TRD. Future trials of iTBS for depression should include discrete measures of suicidality.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Suicídio , Depressão , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Córtex Pré-Frontal , Estimulação Magnética Transcraniana , Resultado do Tratamento
6.
NPJ Schizophr ; 8(1): 2, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35210458

RESUMO

Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.

7.
Neuropsychopharmacology ; 47(5): 1096-1105, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35110687

RESUMO

Response to repetitive transcranial magnetic stimulation (rTMS) among individuals with major depressive disorder (MDD) varies widely. The neural mechanisms underlying rTMS are thought to involve changes in large-scale networks. Whether structural network integrity and plasticity are associated with response to rTMS therapy is unclear. Structural MRIs were acquired from a series of 70 adult healthy controls and 268 persons with MDD who participated in two arms of a large randomized, non-inferiority trial, THREE-D, comparing intermittent theta-burst stimulation to high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). Patients were grouped according to percentage improvement on the 17-item Hamilton Depression Rating Score at treatment completion. For the entire sample and then for each treatment arm, multivariate analyses were used to characterize structural covariance networks (SCN) from cortical gray matter thickness, volume, and surface area maps from T1-weighted MRI. The association between SCNs and clinical improvement was assessed. For both study arms, cortical thickness and volume SCNs distinguished healthy controls from MDD (p = 0.005); however, post-hoc analyses did not reveal a significant association between pre-treatment SCN expression and clinical improvement. We also isolated an anticorrelated SCN between the left DLPFC rTMS target site and the subgenual anterior cingulate cortex across cortical measures (p = 0.0004). Post-treatment change in cortical thickness SCN architecture was associated with clinical improvement in treatment responders (p = 0.001), but not in non-responders. Structural network changes may underpin clinical response to rTMS, and SCNs are useful for understanding the pathophysiology of depression and neural mechanisms of plasticity and response to circuit-based treatments.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Adulto , Depressão/terapia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana , Resultado do Tratamento
8.
Brain Stimul ; 15(2): 291-295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085817

RESUMO

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is entering wider use as a therapeutic intervention for many psychiatric illnesses. The efficacy of this therapeutic intervention may depend on accurately localizing target brain regions. Recent work investigating whole-brain maps of circuits associated with depression and its successful treatment has identified foci of interest within the dorsolateral prefrontal cortex (DLPFC). OBJECTIVE: To create an updated scalp heuristic for localizing the DLPFC based on convergent evidence of lesion and brain stimulation studies in depression. METHODS: Using the standard MNI ICBM152 anatomical template, we localized the scalp sites at minimum Euclidean distance from target MNI coordinates and performed nasion-inion, tragus-tragus, and head-circumference measurements on the anatomical template. We then derived equations to localize these scalp sites. RESULTS: The derived equations to calculate the arc length X and Y for these new targets are as follows: [Y=((NI+TrTr)/2)×0.3167 ; X=HC×0.1359] for the left anterior DLPFC[ Y=((NI+TrTr)/2)×0.2884; X=HC×0.1352] for the right anterior DLPFC[ Y=((NI+TrTr)/2)×0.2480; X=HC×0.1847] for the left posterior DLPFC[ Y=((NI+TrTr)/2)×0.2316 ; X=HC×0.1968] for the right posterior DLPFC CONCLUSIONS: This heuristic may help localize DLPFC targets identified in previous lesion-/stimulation-mapping work. A spreadsheet calculation tool is offered to support use of this heuristic.


Assuntos
Heurística , Córtex Pré-Frontal , Encéfalo , Depressão/terapia , Córtex Pré-Frontal/fisiologia , Couro Cabeludo , Estimulação Magnética Transcraniana
9.
J Clin Psychiatry ; 83(2)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35044731

RESUMO

Objective: To quantitatively synthesize the literature on the effects of repetitive transcranial magnetic stimulation (rTMS) on suicidal ideation (SI) in patients with treatment-resistant depression.Data Sources: A literature search was conducted using PubMed, SCOPUS, Ovid, MEDLINE, Embase, and Web of Science from inception to January 11, 2021, for the keywords repetitive transcranial magnetic stimulation, suicidal ideation, suicidality, treatment-resistant depression, refractory depression, transcranial magnetic stimulation, and brain stimulation.Study Selection: A total of 16 publications were eligible for inclusion. Studies were included that investigated the effects of rTMS in adolescents and/or adults 16 years or older diagnosed with unipolar or bipolar depression with suicidal ideation data before and after rTMS intervention.Data Extraction: Data were extracted and managed using Covidence. Extracted data included authors, publication year, country of origin, study design, patient demographics, primary diagnosis, comorbidities, mean age, outcome assessment instruments, detailed stimulation parameters, sham control procedures, and any serious adverse events related to SI.Results: A quantitative analysis of effect size using Hedges g was calculated for both randomized controlled trials and all other uncontrolled trials. We found a decrease in SI scores in randomized controlled trials (g = 0.158, 95% confidence interval [CI] = -0.078 to 0.393, P = .191), although the effect was not significant. There was a significant decrease in suicidal ideation scores for uncontrolled trials (g = 0.692, 95% CI = 0.463 to 0.922, P < .001).Conclusions: Our findings suggest that rTMS may be an effective treatment for SI in individuals with treatment-resistant depression, although further investigation is warranted.


Assuntos
Transtorno Depressivo Resistente a Tratamento/terapia , Ideação Suicida , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Masculino , Resultado do Tratamento
10.
Bipolar Disord ; 24(1): 10-26, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33949063

RESUMO

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is commonly used in unipolar depression; yet, its evidence in bipolar disorder (BD) is limited. We sought to review the evidence on the use of rTMS across the different stages of BD. METHODS: MEDLINE database was systematically searched using the PubMed interface following the PRISMA guidelines. Inclusion criteria were as follows: (i) randomized clinical trials (RCTs), open-label studies, and case series; (ii) specific evaluation of the treatment outcomes using psychometric scales; (iii) clinical studies in adults; and (iv) articles in the English language. The systematic review has been registered on PROSPERO (CRD42020192788). RESULTS: Thirty-one papers were included in the review. Most studies included participants diagnosed with a bipolar depressive episode (N = 24), have yielded mixed findings, and have yet to reach a consensus on the most effective rTMS protocol. Few studies examined the effect of rTMS during manic (N = 5) or mixed episode (N = 1), or as maintenance treatment (N = 1). The limited data thus far suggest rTMS to be relatively safe and well tolerated. Small sample sizes, heterogeneity among study designs, patients and control groups recruited, rTMS parameters, and outcome measures are among the most significant limitations to these studies. CONCLUSION: The current data regarding the application of rTMS in BD patients remain limited. More adequately powered sham-controlled studies are required to verify its efficacy. Large-scale clinical trials are needed to also determine whether its effects extend to manic and mixed episodes, as well as its role in mood stabilization and amelioration of suicidal behavior.


Assuntos
Transtorno Bipolar , Transtorno Depressivo , Adulto , Afeto , Transtorno Bipolar/etiologia , Transtorno Bipolar/terapia , Humanos , Mania , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
11.
Artigo em Inglês | MEDLINE | ID: mdl-34311121

RESUMO

BACKGROUND: Older adults with late-life depression (LLD) often experience incomplete or lack of response to first-line pharmacotherapy. The treatment of LLD could be improved using objective biological measures to predict response. Transcranial magnetic stimulation (TMS) can be used to measure cortical excitability, inhibition, and plasticity, which have been implicated in LLD pathophysiology and associated with brain stimulation treatment outcomes in younger adults with depression. TMS measures have not yet been investigated as predictors of treatment outcomes in LLD or pharmacotherapy outcomes in adults of any age with depression. METHODS: We assessed whether pretreatment single-pulse and paired-pulse TMS measures, combined with clinical and demographic measures, predict venlafaxine treatment response in 76 outpatients with LLD. We compared the predictive performance of machine learning models including or excluding TMS predictors. RESULTS: Two single-pulse TMS measures predicted venlafaxine response: cortical excitability (neuronal membrane excitability) and the variability of cortical excitability (dynamic fluctuations in excitability levels). In cross-validation, models using a combination of these TMS predictors, clinical markers of treatment resistance, and age classified patients with 73% ± 11% balanced accuracy (average correct classification rate of responders and nonresponders; permutation testing, p < .005); these models significantly outperformed (corrected t test, p = .025) models using clinical and demographic predictors alone (60% ± 10% balanced accuracy). CONCLUSIONS: These preliminary findings suggest that single-pulse TMS measures of cortical excitability may be useful predictors of response to pharmacotherapy in LLD. Future studies are needed to confirm these findings and determine whether combining TMS predictors with other biomarkers further improves the accuracy of predicting LLD treatment outcome.

12.
Cereb Cortex ; 32(8): 1653-1667, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-34519333

RESUMO

Theta-gamma coupling (TGC) is a neurophysiologic mechanism that supports working memory (WM). TGC is associated with N-back performance, a WM task. Similar to TGC, theta and alpha event-related synchronization (ERS) and desynchronization (ERD) are also associated with WM. Few studies have examined the longitudinal relationship between WM performance and TGC, ERS, or ERD. This study aimed to determine if changes in WM performance are associated with changes in TGC (primary aim), as well as theta and alpha ERS or ERD over 6 to 12 weeks. Participants included 62 individuals aged 60 and older with no neuropsychiatric conditions or with remitted Major Depressive Disorder (MDD) and no cognitive disorders. TGC, ERS, and ERD were assessed using electroencephalography (EEG) during the N-back task (3-back condition). There was an association between changes in 3-back performance and changes in TGC, alpha ERD and ERS, and theta ERS in the control group. In contrast, there was only a significant association between changes in 3-back performance and changes in TGC in the subgroup with remitted MDD. Our results suggest that the relationship between WM performance and TGC is stable over time, while this is not the case for changes in theta and alpha ERS and ERD.


Assuntos
Transtornos Cognitivos , Transtorno Depressivo Maior , Idoso , Cognição , Sincronização Cortical , Eletroencefalografia , Humanos , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade
13.
J ECT ; 38(1): 52-59, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34519681

RESUMO

OBJECTIVES: The COVID-19 pandemic has disrupted the provision of essential and potentially life-saving procedural treatments such as electroconvulsive therapy (ECT). We surveyed ECT providers across Canada to understand how the first wave of the pandemic affected ECT delivery between mid-March 2020 and mid-May 2020. METHODS: The survey was administered to ECT team members and decision makers at 107 Canadian health care centers with a focus on 5 domains: operations, decision-making, hospital resources, ECT procedure, and patient impact. Responses were obtained from 72 institutions, and collected answers were used to derive representative responses reflecting the situation at each ECT center. For specific domains, responses were split into 2 databases representing the perspective of psychiatrists (n = 67 centers) and anesthesiologists (n = 24 centers). RESULTS: Provision of ECT decreased in 64% centers and was completely suspended in 27% of centers after the onset of the pandemic. Outpatient and maintenance ECT were more affected than inpatient and acute ECT. Programs reported a high level of collaboration between psychiatry and hospital leadership (59%) but a limited input from clinical ethicists (18%). Decisions were mostly made ad hoc leading to variability across institutions in adopted resource allocation, physical location of ECT delivery, and triaging frameworks. The majority of centers considered ECT to be aerosol-generating and incorporated changes to airway management. CONCLUSIONS: Electroconvulsive therapy services in Canada were markedly disrupted by the COVID-19 pandemic. The variability in decision-making across centers warrants the development of a rational approach toward offering ECT in pandemic contexts.


Assuntos
COVID-19 , Eletroconvulsoterapia , Canadá , Eletroconvulsoterapia/métodos , Humanos , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
14.
J Affect Disord ; 301: 273-280, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34942227

RESUMO

BACKGROUND: Recently, a small literature has emerged suggesting that repetitive transcranial magnetic stimulation (rTMS) may offer benefit for MDD even in BPD patients, perhaps by enhancing cognitive control, and/or disrupting excessive 'non-reward' activity in right orbitofrontal regions. This study aimed primarily to assess the therapeutic effects of dorsomedial prefrontal cortex (DMPFC)-rTMS against MDD symptoms in BPD patients, and secondarily to assess whether the therapeutic effects ensued via mechanisms of reduced impulsivity and core BPD pathology on clinical scales (BIS-11, ZAN-BPD) or of reduced alpha- and theta-band activity on EEG recordings of right orbitofrontal cortex.. METHODS: In a crossover-design trial, 20 BPD patients with MDD underwent 2 × 30 session/15 day blocks of either active-then-sham or sham-then-active bilateral 20 Hz DMPFC-rTMS. RESULTS: Sixteen out of 20 patients completed treatment. A significant (p = 0.00764) crossover effect was detected, with overall reductions in HamD17 score from 23.1±SD3.1 to 10.75±SD5.8. Nine out of 16 (56.3%) treatment completers achieved response (>50% improvement) and 6/16 (37.5%) achieved remission (HamD≤7), maintained at 1 month followup. BIS-11 scores remained unchanged, and ZAN-BPD scores improved similarly in both groups with no significant crossover effect. Change in low-band power over right orbitofrontal regions correlated with clinical improvement. LIMITATIONS: This was a crossover study with a small sample size. A randomized controlled trial with larger sample size will be needed to establish the efficacy more definitively. CONCLUSIONS: The results suggest efficacy for DMPFC-rTMS in treating MDD in BPD, and provide a foundation for a larger future trial.


Assuntos
Transtorno da Personalidade Borderline , Transtorno Depressivo Maior , Transtorno da Personalidade Borderline/etiologia , Transtorno da Personalidade Borderline/terapia , Estudos Cross-Over , Depressão , Transtorno Depressivo Maior/psicologia , Humanos , Projetos Piloto , Córtex Pré-Frontal , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
15.
Trials ; 22(1): 906, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895296

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood. METHODS/DESIGN: This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity. DISCUSSION: ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT03191058 . Registered on June 19, 2017.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Neurofisiologia , Biomarcadores , Depressão , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/diagnóstico , Convulsões/terapia
16.
Trials ; 22(1): 786, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749782

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure. METHODS: In this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach. DISCUSSION: Positive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy. TRIAL STATUS: Enrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT03191058 , Registered on June 19, 2017. Primary sponsor: Daniel Blumberger (DMB), Principal Investigator Daniel.Blumberger@camh.ca , 416-535-8501 x 33662 Contact for public queries: DMB, Daniel.Blumberger@camh.ca Contact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Adolescente , Adulto , Depressão , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/terapia , Eletroconvulsoterapia/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/diagnóstico , Convulsões/terapia , Resultado do Tratamento
17.
Front Neurosci ; 15: 711542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690671

RESUMO

Altered excitatory and inhibitory neurotransmission has been implicated in autism spectrum disorder (ASD). Interventions using repetitive transcranial magnetic stimulation (rTMS) to enhance or inhibit cortical excitability are under study for various targets, though the mechanistic effects of rTMS have yet to be examined in ASD. Here, we examined whether an excitatory rTMS treatment course modulates glutamatergic (Glx) or γ-aminobutyric acid (GABA) metabolite levels in emerging adults with ASD. Twenty-eight participants with ASD and executive function impairment [23.3 ± 4.69 years; seven-female] underwent two magnetic resonance spectroscopy (MRS) scans of the left dorsolateral prefrontal cortex (DLPFC). MRS scans were acquired before and after participants with ASD were randomized to receive a 20-session course of active or sham rTMS to the DLPFC. Baseline MRS data was available for 19 typically developing controls [23.8 ± 4.47 years; six-female]. Metabolite levels for Glx and GABA+ were compared between ASD and control groups, at baseline, and metabolite level change, pre-to-post-rTMS treatment, was compared in ASD participants that underwent active vs. sham rTMS. Absolute change in Glx was greater in the active vs. sham-rTMS group [F (1, 19) = 6.54, p = 0.02], though the absolute change in GABA+ did not differ between groups. We also examined how baseline metabolite levels related to pre/post-rTMS metabolite level change, in the active vs. sham groups. rTMS group moderated the relation between baseline Glx and pre-to-post-rTMS Glx change, such that baseline Glx predicted Glx change in the active-rTMS group only [b = 1.52, SE = 0.32, t (18) = 4.74, p < 0.001]; Glx levels increased when baseline levels were lower, and decreased when baseline levels were higher. Our results indicate that an interventional course of excitatory rTMS to the DLPFC may modulate local Glx levels in emerging adults with ASD, and align with prior reports of glutamatergic alterations following rTMS. Interventional studies that track glutamatergic markers may provide mechanistic insights into the therapeutic potential of rTMS in ASD. Clinical Trial Registration: Clinicaltrials.gov (ID: NCT02311751), https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751.

18.
Mindfulness (N Y) ; : 1-13, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34630733

RESUMO

OBJECTIVES: Individuals with subjective memory complaints and symptoms of depression and/or anxiety are at high risk for further cognitive decline, and possible progression to dementia. Low-burden interventions to help slow or prevent cognitive decline in this high-risk group are needed. The objective of this study is to assess the feasibility of combining Mindfulness-Based Stress Reduction (MBSR) with transcranial direct current stimulation (tDCS) to increase putative benefits of MBSR for cognitive function and everyday mindfulness in depressed or anxious older adults with subjective cognitive decline. METHODS: We conducted a two-site pilot double-blind randomized sham-controlled trial, combining active MBSR with either active or sham tDCS. The intervention included weekly in-class group sessions at the local university hospital and daily at-home practice. Anodal tDCS was applied for 30 min during MBSR meditative practice, both in-class and at-home. RESULTS: Twenty-six individuals with subjective cognitive complaints and symptoms of depression and/or anxiety were randomized to active (n = 12) or sham tDCS (n = 14). The combination of MBSR and tDCS was safe and well tolerated, though at-home adherence and in-class attendance were variable. While they were not statistically significant, the largest effect sizes for active vs. sham tDCS were for everyday mindfulness (d = 0.6) and social functioning (d = 0.9) (F (1,21) = 3.68, p = 0.07 and F (1,21) = 3.9, p = 0.06, respectively). CONCLUSIONS: Our findings suggest that it is feasible and safe to combine tDCS with MBSR in older depressed and anxious adults, including during remote, at-home use. Furthermore, tDCS may enhance MBSR via transferring its meditative learning and practice into increases in everyday mindfulness. Future studies need to improve adherence to MBSR with tDCS. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03653351 and NCT03680664). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01764-9.

19.
J Clin Psychiatry ; 82(6)2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34670025

RESUMO

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute treatment, there are no published studies of continuation MST for the prevention of relapse.Methods: Patients with TRD with a DSM-IV diagnosis of major depressive disorder or bipolar disorder who met response criteria after acute MST were offered continuation MST in a prospective, open-label trial between February 2012 and June 2019. They received 12 continuation MST sessions with decreasing frequency over the course of 6 months, with additional booster sessions if their depression symptoms started to worsen. The primary outcome was relapse of depression or psychiatric hospitalization. Secondary outcomes included relapse of suicidal ideation and neurocognitive outcomes.Results: Thirty participants completing at least one assessment during continuation MST were included in the analysis; 10 (33.3%) relapsed, with no significant differences in survival distributions between unipolar and bipolar groups (χ2 = 0.3, P = .58). Mean (SD) survival time was 18.6 (1.6) weeks. All 17 participants who achieved resolution of baseline suicidality after acute MST remained free of suicidality during the continuation phase. Except for improvement in verbal fluency, neurocognitive test scores did not change during continuation MST.Conclusions: During 6 months of continuation MST, two-thirds of participants sustained improvements in depressive symptoms without any adverse cognitive effects. Future studies of continuation MST are warranted, particularly in comparison to ECT.Trial Registration: ClinicalTrials.gov identifier: NCT01596608.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Prevenção Secundária , Estimulação Magnética Transcraniana , Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Continuidade da Assistência ao Paciente , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/psicologia , Transtorno Depressivo Resistente a Tratamento/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Escalas de Graduação Psiquiátrica , Prevenção Secundária/métodos , Prevenção Secundária/estatística & dados numéricos , Ideação Suicida , Estimulação Magnética Transcraniana/efeitos adversos , Estimulação Magnética Transcraniana/métodos , Estimulação Magnética Transcraniana/estatística & dados numéricos , Comportamento Verbal
20.
Nat Med ; 27(10): 1687-1688, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34635858
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