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Although 10-Hz repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression, we have yet to fully understand the mechanism through which rTMS induces therapeutic and durable changes in the brain. Two competing theories have emerged suggesting that 10-Hz rTMS induces N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP), or alternatively, removal of inhibitory gamma-aminobutyric acid receptors (GABARs). We examined these two proposed mechanisms of action in the human motor cortex in a double-blind, randomized, four-arm crossover study in healthy subjects. We tested motor-evoked potentials (MEPs) before and after 10-Hz rTMS in the presence of four drugs separated by 1-week each: placebo, NMDAR partial agonist d-cycloserine (DCS 100mg), DCS 100mg + NMDAR partial antagonist dextromethorphan (DMO 150mg; designed to "knock down" DCS-mediated facilitation), and GABAR agonist lorazepam (LZP 2.5mg). NMDAR agonism by DCS enhanced rTMS-induced cortical excitability more than placebo. This enhancement was blocked by combining DCS with NMDAR antagonist, DMO. If GABARs are removed by rTMS, GABAR agonism via LZP should lack its inhibitory effect yielding higher post/pre MEPs. However, MEPs were reduced after rTMS indicating stability of GABAR numbers. These data suggest that 10-Hz rTMS facilitation in the healthy motor cortex may enact change in the brain through NMDAR-mediated LTP-like mechanisms rather than through GABAergic reduction.
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In recent history, the world has witnessed a trend towards liberalization of abortion laws driven by an increasing understanding of the negative personal and public health consequences of criminalizing abortion. By contrast, several countries have recently implemented restrictive reproductive laws, joining the 112 countries where access to abortion care is banned completely or with narrow exceptions. On June 24, 2022, the US Supreme Court ruling in Dobbs v Jackson Women's Health Organization overturned its landmark decisions in Roe v Wade that established abortion until the point of viability of the fetus as a constitutional right. After Roe v Wade having been overturned, it is projected that many women in the USA will be prevented from accessing safe abortion care. Importantly, abortion bans not only impose constraints on patient autonomy, they also restrict physicians' ability to practice evidence-based medicine, which will negatively impact psychiatric care. It is therefore crucial for the practicing psychiatrist to be familiar with this new legal landscape. In this Personal View, we aim to provide a topical overview to help clinicians gain a clear understanding of legal, clinical, and ethical responsibilities, focusing on the USA. We also discuss the reality that psychiatrists might be called upon to determine medical necessity for an abortion on psychiatric grounds, which is new for most US psychiatrists. We predict that psychiatrists will be confronted with very difficult situations in which lawful and ethical conduct might be incongruent, and that abortion bans will result in greater numbers of patients needing psychiatric care from a system that is ill-prepared for additional demands.
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OBJECTIVE: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. METHODS: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized. RESULTS: Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results. CONCLUSIONS: The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response.
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Farmacogenética , Humanos , Farmacogenética/métodos , Antidepressivos/uso terapêutico , Ensaios Clínicos como Assunto , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/genética , Testes Farmacogenômicos/métodosRESUMO
Recent work has found that the presence of transient, oscillatory burst-like events, particularly within the beta band (15-29 Hz), is more closely tied to disease state and behavior across species than traditional electroencephalography (EEG) power metrics. This study sought to examine whether features of beta events over frontoparietal electrodes were associated with early life stress (ELS) and the related clinical presentation. Eighteen adults with documented ELS (n = 18; ELS + ) and eighteen adults without documented ELS (n = 18; ELS-) completed eyes-closed resting state EEG as part of their participation in a larger childhood stress study. The rate, power, duration, and frequency span of transient oscillatory events were calculated within the beta band at five frontoparietal electrodes. ELS variables were positively associated with beta event rate at Fp2 and beta event duration at Pz, in that greater ELS was associated with higher resting rates and longer durations. These beta event characteristics were used to successfully distinguish between ELS + and ELS- groups. In an independent clinical dataset (n = 25), beta event power at Pz was positively correlated with ELS. Beta events deserve ongoing investigation as a potential disease marker of ELS and subsequent psychiatric treatment outcomes.
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Ritmo beta , Eletroencefalografia , Estresse Psicológico , Humanos , Feminino , Adulto , Masculino , Ritmo beta/fisiologia , Estresse Psicológico/fisiopatologia , Eletroencefalografia/métodos , Lobo Frontal/fisiopatologia , Lobo Parietal/fisiopatologia , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Determining when to recommend a change in treatment regimen due to insufficient improvement is a common challenge in therapeutics. METHODS: In a sample of 7215 patients with major depressive disorder treated with transcranial magnetic stimulation (TMS) and with PHQ-9 scores before, during and after the course, 3 groups were identified based on number of acute course sessions: exactly 36 sessions (N = 3591), more than 36 sessions (N = 975), and less than 36 sessions (N = 2649). Two techniques were used to determine thresholds for percentage change in PHQ-9 scores at assessments after 10, 20, and 30 sessions that optimized prediction of endpoint response status: the Youden index and fixing the false positive rate at 10%. Positive and negative predictive values were calculated to assess the accuracy of identifying final nonresponders and responders, respectively. RESULTS: There was greater accuracy in predicting final response than nonresponse, especially in the groups that had at least 36 sessions. Substantial proportions of patients with low levels of early improvement were classified as responders at the end of treatment. LIMITATIONS: The findings should be validated with clinician ratings using a more comprehensive depression severity scale. CONCLUSIONS: Manifesting clinical improvement early in the TMS course is strongly predictive of final status as a responder, while lack of early improvement is a relatively poor indicator of final nonresponse status. The predictive value of lack of early symptomatic improvement is too low to make reliable recommendations regarding changes in treatment regimen.
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Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/diagnóstico , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for individuals with major depressive disorder (MDD) who have not improved with standard therapies. However, only 30-45% of patients respond to rTMS. Predicting response to rTMS will benefit both patients and providers in terms of prescribing and targeting treatment for maximum efficacy and directing resources, as individuals with lower likelihood of response could be redirected to more suitable treatment alternatives. In this exploratory study, our goal was to use proton magnetic resonance spectroscopy to examine how glutamate (Glu), Glx, and total N-acetylaspartate (tNAA) predict post-rTMS changes in overall MDD severity and symptoms, and treatment response. Metabolites were measured in a right dorsal anterior cingulate cortex voxel prior to a standard course of 10 Hz rTMS to the left DLPFC in 25 individuals with MDD. MDD severity and symptoms were evaluated via the Inventory of Depression Symptomatology Self-Report (IDS-SR). rTMS response was defined as ≥50% change in full-scale IDS-SR scores post treatment. Percent change in IDS-SR symptom domains were evaluated using principal component analysis and established subscales. Generalized linear and logistic regression models were used to evaluate the relationship between baseline Glu, Glx, and tNAA and outcomes while controlling for age and sex. Participants with baseline Glu and Glx levels in the lower range had greater percent change in full scale IDS-SR scores post-treatment (p < 0.001), as did tNAA (p = 0.007). Low glutamatergic metabolite levels also predicted greater percent change in mood/cognition symptoms (p ≤ 0.001). Low-range Glu, Glx, and tNAA were associated with greater improvement on the immuno-metabolic subscale (p ≤ 0.003). Baseline Glu predicted rTMS responder status (p = 0.025) and had an area under the receiving operating characteristic curve of 0.81 (p = 0.009), demonstrating excellent discriminative ability. Baseline Glu, Glx, and tNAA significantly predicted MDD improvement after rTMS; preliminary evidence also demonstrates metabolite association with symptom subdomain improvement post-rTMS. This work provides feasibility for a personalized medicine approach to rTMS treatment selection, with individuals with Glu levels in the lower range potentially being the best candidates.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Ácido Glutâmico , Estimulação Magnética Transcraniana , Depressão , BiomarcadoresRESUMO
The emergence of psychiatric symptoms is a common consequence of childhood stress exposure. However, there are a dearth of reliable clinical hallmarks or physiological biomarkers to predict post-trauma symptom emergence. The objective of this study was to examine if childhood stressors and stress-related symptoms are associated with altered midline theta power (MTP) during cognitive control demands, and how these associations interact with gender and early adversity. N = 53 children (ages 9-13 years old) from a longitudinal study of children maltreated during early childhood and non-maltreated children participated in this study. EEG recorded neural activity during a Zoo-Themed Go/No-Go task. Stress-related symptoms, recent stressful events, and other adversity experiences were identified. MTP was analyzed with clinical variables in a series of follow-up analyses. The number of stressors in the past six months was negatively correlated with MTP in those with low preschool adversity, but not in those with high preschool adversity. MTP was higher in girls than in boys, and the associations of MTP with stressors and symptoms were moderated by gender. MTP was negatively associated with stressors in the past six months in girls, while in boys, MTP was associated with stress-related symptoms. Childhood stressful events were associated with reduced MTP during cognitive control demands, and this was finding was moderated by gender and early life adversity. These preliminary findings suggest that boys and girls may process stressful experiences in distinct ways, and preschool adversity may potentially blunt the interaction between current stress and neural dynamics. However, ongoing investigation is needed.
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Depressão , Estresse Psicológico , Masculino , Criança , Feminino , Humanos , Pré-Escolar , Adolescente , Estudos Longitudinais , Estresse Psicológico/psicologia , Depressão/psicologia , Escolaridade , CogniçãoRESUMO
Repetitive transcranial magnetic stimulation (rTMS) is an established clinical treatment for major depressive disorder (MDD) that has also been found to improve aspects of executive functioning. The objective of this study was to examine whether oscillatory burst-like events within the beta band (15-29 Hz) prior to treatment could predict subsequent change in self-reported executive dysfunction (EDF) across a clinical course of rTMS for MDD. Twenty-eight adults (64% female) with MDD completed the self-report Frontal Systems Behavior Scale (FrSBe) and provided eyes-closed resting-state electroencephalography (EEG) before and after a clinical course of rTMS therapy for primary MDD. The rate, power, duration, and frequency span of transient EEG measured oscillatory beta events were calculated. Events within delta/theta and alpha bands were examined to assess for beta specificity. After controlling for improvement in primary depressive symptoms, a lower rate of beta events at F3, Fz, F4, and Cz prior to rTMS treatment was associated with a larger improvement in EDF after rTMS treatment. In addition, a decrease in beta event rate at Fz pre-to-post treatment was associated with a larger improvement in EDF after treatment. Results were largely specific to the beta band. In this study, the rate of frontrocentral beta events prior to treatment significantly predicted the likelihood of subsequent improvement in EDF symptoms following a clinical course of rTMS for MDD. These preliminary findings suggest the potential utility of EEG measured beta events and rTMS for targeting EDF across an array of neuropsychiatric disorders.
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Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Adulto , Humanos , Feminino , Masculino , Estimulação Magnética Transcraniana/métodos , Transtorno Depressivo Maior/terapia , Depressão/terapia , Córtex Pré-Frontal , Progressão da Doença , Resultado do TratamentoRESUMO
BACKGROUND: The number of sessions in an acute TMS course for major depressive disorder (MDD) is greater than in the earlier randomized controlled trials. OBJECTIVE: To compare clinical outcomes in groups that received differing numbers of TMS sessions. METHODS: From a registry sample (N = 13,732), data were extracted for 7215 patients treated for MDD with PHQ-9 assessments before and after their TMS course. Groups were defined by number of acute course treatment sessions: 1-19 (N = 658), 20-29 (N = 616), 30-35 (N = 1375), 36 (N = 3591), 37-41 (N = 626), or >41 (N = 349) and compared in clinical outcomes at endpoint and at fixed intervals (after 10, 20, 30, and 36 sessions). The impact of additional treatments beyond 36 sessions was also examined. RESULTS: Groups that received fewer than 30 sessions had inferior endpoint outcomes than all other groups. PHQ-9 symptom reduction was greatest in the group that ended treatment at 36 sessions. The extended treatment groups (>36 sessions) differed from all other groups by manifesting less antidepressant response early in the course and had a slower but steady rate of improvement over time. Extending treatment beyond 36 sessions was associated with further improvement without evidence of a plateau. CONCLUSIONS: In real-world practice, there are strong relations between the number of TMS sessions in a course and the magnitude of symptom reduction. Courses with less than 30 sessions are associated with diminished benefit. Patients with longer than standard courses typically show less initial improvement and a more gradual trajectory, but meaningful benefit accrues with treatment beyond 36 sessions.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/terapia , Estimulação Magnética Transcraniana , Resultado do Tratamento , AntidepressivosRESUMO
Investigators from minoritized backgrounds are underrepresented in psychiatric research. That underrepresentation contributes to disparities in outcomes of access to mental health care. Drawing on lived experience, scholarly qualitative reports, and empirical data, the authors review how the underrepresentation of minoritized researchers arises from interlocking, self-reinforcing effects of structural biases in our research training and funding institutions. Minoritized researchers experience diminished early access to advanced training and opportunities, stereotype threats and microaggressions, isolation due to lack of peers and senior mentors, decreased access to early funding, and unique community and personal financial pressures. These represent structural racism-a system of institutional assumptions and practices that perpetuates race-based disparities, in spite of those institutions' efforts to increase diversity and in contradiction to the values that academic leaders outwardly espouse. The authors further review potential approaches to reversing these structural biases, including undergraduate-focused research experiences, financial support for faculty who lead training/mentoring programs, targeted mentoring through scholarly societies, better use of federal diversity supplement funding, support for scientific reentry, cohort building, diversity efforts targeting senior leadership, and rigorous examination of hiring, compensation, and promotion practices. Several of these approaches have empirically proven best practices and models for dissemination. If implemented alongside outcome measurement, they have the potential to reverse decades of structural bias in psychiatry and psychiatric research.
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Pesquisa Biomédica , Tutoria , Humanos , Grupos Minoritários , Racismo Sistêmico , Recursos HumanosRESUMO
Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5 Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre- to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.
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Transtorno Depressivo Maior , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtorno Depressivo Maior/terapia , Estimulação Magnética Transcraniana , Transtornos de Estresse Pós-Traumáticos/terapia , Córtex Pré-Frontal/fisiologia , Eletroencefalografia , Resultado do Tratamento , BiomarcadoresRESUMO
Motor skill learning has been linked to functional and structural changes in the brain. Musicians and athletes undergo intensive motor training through the practice of an instrument or sport and have demonstrated use-dependent plasticity that may be subserved by long-term potentiation (LTP) processes. We know less, however, about whether the brains of musicians and athletes respond to plasticity-inducing interventions, such as repetitive transcranial magnetic stimulation (rTMS), differently than those without extensive motor training. In a pharmaco-rTMS study, we evaluated motor cortex excitability before and after an rTMS protocol in combination with oral administration of D-cycloserine (DCS) or placebo. In a secondary covariate analysis, we compared results between self-identified musicians and athletes (M&As) and non-musicians and athletes (non-M&As). Three TMS measures of cortical physiology were used to evaluate plasticity. We found that M&As did not have higher baseline corticomotor excitability. However, a plasticity-inducing protocol (10-Hz rTMS in combination with DCS) strongly facilitated motor-evoked potentials (MEPs) in M&As, but only weakly in non-M&As. Placebo and rTMS produced modest facilitation in both groups. Our findings suggest that motor practice and learning create a neuronal environment more responsive to plasticity-inducing events, including rTMS. These findings may explain one factor contributing to the high inter-individual variability found with MEP data. Greater capacity for plasticity holds implications for learning paradigms, such as psychotherapy and rehabilitation, by facilitating LTP-like activation of key networks, including recovery from neurological/mental disorders.
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Potenciação de Longa Duração , Plasticidade Neuronal , Humanos , Atletas , Potencial Evocado Motor/fisiologia , Aprendizagem , Plasticidade Neuronal/fisiologia , Estimulação Magnética Transcraniana/métodosRESUMO
Introduction: Synapses and spines play a significant role in major depressive disorder (MDD) pathophysiology, recently highlighted by the rapid antidepressant effect of ketamine and psilocybin. According to the Bayesian brain and interoception perspectives, MDD is formalized as being stuck in affective states constantly predicting negative energy balance. To understand how spines and synapses relate to the predictive function of the neocortex and thus to symptoms, we used the temporal memory (TM), an unsupervised machine-learning algorithm. TM models a single neocortical layer, learns in real-time, and extracts and predicts temporal sequences. TM exhibits neocortical biological features such as sparse firing and continuous online learning using local Hebbian-learning rules. Methods: We trained a TM model on random sequences of upper-case alphabetical letters, representing sequences of affective states. To model depression, we progressively destroyed synapses in the TM model and examined how that affected the predictive capacity of the network. We found that the number of predictions decreased non-linearly. Results: Destroying 50% of the synapses slightly reduced the number of predictions, followed by a marked drop with further destruction. However, reducing the synapses by 25% distinctly dropped the confidence in the predictions. Therefore, even though the network was making accurate predictions, the network was no longer confident about these predictions. Discussion: These findings explain how interoceptive cortices could be stuck in limited affective states with high prediction error. Connecting ketamine and psilocybin's proposed mechanism of action to depression pathophysiology, the growth of new synapses would allow representing more futuristic predictions with higher confidence. To our knowledge, this is the first study to use the TM model to connect changes happening at synaptic levels to the Bayesian formulation of psychiatric symptomatology. Linking neurobiological abnormalities to symptoms will allow us to understand the mechanisms of treatments and possibly, develop new ones.
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Background: Caffeine is a widely used psychostimulant. In the brain, caffeine acts as a competitive, non-selective adenosine receptor antagonist of A1 and A2A, both known to modulate long-term potentiation (LTP), the cellular basis of learning and memory. Repetitive transcranial magnetic stimulation (rTMS) is theorized to work through LTP induction and can modulate cortical excitability as measured by motor evoked potentials (MEPs). The acute effects of single caffeine doses diminish rTMS-induced corticomotor plasticity. However, plasticity in chronic daily caffeine users has not been examined. Method: We conducted a post hoc secondary covariate analysis from two previously published plasticity-inducing pharmaco-rTMS studies combining 10 Hz rTMS and D-cycloserine (DCS) in twenty healthy subjects. Results: In this hypothesis-generating pilot study, we observed enhanced MEP facilitation in non-caffeine users compared to caffeine users and placebo. Conclusion: These preliminary data highlight a need to directly test the effects of caffeine in prospective well-powered studies, because in theory, they suggest that chronic caffeine use could limit learning or plasticity, including rTMS effectiveness.
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Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre-to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.
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Objective: To determine the extent that treatment with transcranial magnetic stimulation (TMS) in diverse clinical settings has anxiolytic and antidepressant effects in patients with major depressive disorder (MDD) and moderate-to-severe anxiety symptoms and to contrast anxious and nonanxious depression subgroups in antidepressant effects.Methods: Within the NeuroStar Advanced Therapy System Clinical Outcomes Registry, 1,820 patients were identified with a diagnosis of MDD (using ICD-9, ICD-10, or DSM-IV) who completed the Patient Health Questionnaire-9 (PHQ-9) and Global Anxiety Disoder-7 scale (GAD-7) at baseline and following at least 1 TMS treatment between May 2016 and January 2021. Anxious depression was defined as a baseline GAD-7 score of 10 or greater (n = 1,514) and nonanxious depression by GAD-7 scores below this threshold (n = 306). Intent-to-treat and Completer samples were defined for patients treated with any TMS protocol and for the subgroup treated only with high-frequency left dorsolateral prefrontal cortex stimulation.Results: Patients with anxious depression showed clinically meaningful anxiolytic and antidepressant effects, averaging approximately 50% or greater reductions in both GAD-7 and PHQ-9 scores following TMS in all samples. The anxious and nonanxious depression groups had equivalent absolute improvement in PHQ-9 scores (P values ≥ .29). However, the anxious group had higher scores both at baseline and following TMS resulting in significantly lower categorical rates of response (P values < .02) and remission (P values < .001) in depressive symptoms. Among those with anxious depression, the change in anxiety and depression symptoms strongly covaried (r1512 = 0.75, P < .001).Conclusions: Routine TMS delivered in diverse clinical settings results in marked anxiolytic and antidepressant effects in patients with anxious depression. The extent of improvement in anxiety and depression symptoms strongly covaries.
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Ansiolíticos , Transtorno Depressivo Maior , Humanos , Depressão , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/diagnóstico , Estimulação Magnética Transcraniana , Resultado do Tratamento , Antidepressivos/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included. RESULTS: A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis." CONCLUSIONS: There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.
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Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/terapia , Biomarcadores , Fenótipo , Imageamento por Ressonância Magnética , Projetos de PesquisaRESUMO
Technology is ubiquitous in society and is now being extensively used in mental health applications. Both assessment and treatment strategies are being developed and deployed at a rapid pace. The authors review the current domains of technology utilization, describe standards for quality evaluation, and forecast future developments. This review examines technology-based assessments of cognition, emotion, functional capacity and everyday functioning, virtual reality approaches to assessment and treatment, ecological momentary assessment, passive measurement strategies including geolocation, movement, and physiological parameters, and technology-based cognitive and functional skills training. There are many technology-based approaches that are evidence based and are supported through the results of systematic reviews and meta-analyses. Other strategies are less well supported by high-quality evidence at present, but there are evaluation standards that are well articulated at this time. There are some clear challenges in selection of applications for specific conditions, but in several areas, including cognitive training, randomized clinical trials are available to support these interventions. Some of these technology-based interventions have been approved by the U.S. Food and Drug administration, which has clear standards for which types of applications, and which claims about them, need to be reviewed by the agency and which are exempt.
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Transtornos Cognitivos , Saúde Mental , Humanos , Revisões Sistemáticas como Assunto , Emoções , TecnologiaRESUMO
[This corrects the article DOI: 10.3389/fpsyt.2022.877574.].