A pandemic toll in frail older adults: Higher odds of incident and persistent common mental disorders in the ELSA-Brasil COVID-19 mental health cohort.

INTRODUCTION: We aimed to investigate the association of frailty with persistent and incident common mental disorders (CMD) in older adults during the pandemic. METHODS: We included 706 older adults who participated in the onsite wave of the ELSA-Brasil study (2017-2019) and the online COVID-19 assessment (May-July 2020). CMD were assessed in both waves by the Clinical Interview Schedule-Revised. Frailty was defined according to the physical phenotype and Frailty Index in the 2017-2019 wave. Logistic regression was used to investigate the association of frailty with persistent and incident CMD, adjusted for sociodemographics. RESULTS: Frailty according to both definitions were associated with persistent CMD (Frailty Index: OR = 8.61, 95 % CI = 4.08-18.18; physical phenotype: OR = OR = 23.67, 95 % CI = 7.08-79.15), and incident CMD (Frailty Index: OR = 2.79, 95 % CI = 1.15-6.78; physical phenotype OR = 4.37, 95 % CI = 1.31-14.58). The exclusion of exhaustion (that overlaps with psychiatric symptoms) from the frailty constructs did not change the association between frailty and persistent CMD, although the associations with indent CMD were no longer significant. LIMITATIONS: Fluctuations in CMD status were not captured between both assessments. CONCLUSION: Frailty status before the COVID-19 outbreak was associated with higher odds of persistent and incident CMD in older adults during the pandemic first wave. Identifying individuals at higher risk of mental burden can help prioritize resources allocation and management.

Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort.

BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center. METHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders. RESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ß = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety (ß = -0.37, 99.5% CI -0.48 to -0.26), and stress (ß = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk. CONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.

Brain Perfusion Alterations Induced by Standalone and Combined Non-Invasive Brain Stimulation over the Dorsolateral Prefrontal Cortex.

Non-invasive brain stimulation (NIBS) interventions are promising for the treatment of psychiatric disorders. Notwithstanding, the NIBS mechanisms of action over the dorsolateral prefrontal cortex (DLPFC), a hub that modulates affective and cognitive processes, have not been completely mapped. We aimed to investigate regional cerebral blood flow (rCBF) changes over the DLPFC and the subgenual anterior cingulate cortex (sgACC) of different NIBS protocols using Single-Photon Emission Computed Tomography (SPECT). A factorial, within-subjects, double-blinded study was performed. Twenty-three healthy subjects randomly underwent four sessions of NIBS applied once a week: transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), combined tDCS + iTBS and placebo. The radiotracer 99m-Technetium-ethylene-cysteine-dimer was injected intravenously during the NIBS session, and SPECT neuroimages were acquired after the session. Results revealed that the combination of tDCS + iTBS increased right sgACC rCBF. Cathodal and anodal tDCS increased and decreased DLPFC rCBF, respectively, while iTBS showed no significant changes compared to the placebo. Our findings suggest that the combined protocol might optimize the activity in the right sgACC and encourage future trials with neuropsychiatric populations. Moreover, mechanistic studies to investigate the effects of tDCS and iTBS over the DLPFC are required.

The Effects of Transcranial Direct Current Stimulation in Obsessive-Compulsive Disorder Symptoms: A Meta-Analysis and Integrated Electric Fields Modeling Analysis.

Transcranial direct current stimulation (tDCS) has been showing promising effects for the treatment of obsessive-compulsive disorder (OCD), but there is still no conclusion on its efficacy for this disorder. We performed a systematic review and meta-analysis of trials using tDCS for OCD and a computer modeling analysis to evaluate the electric field (EF) strengths of different electrode assemblies in brain regions of interest (ROIs) (PROSPERO-42021262465). PubMed/MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception to 25 September 2022. Randomized controlled trials (RCTs) and open-label studies were included. The primary aim was the effect size (Hedges' g) of continuous outcomes and potential moderators of response. For EF modeling, SimNIBS software was used. Four RCTs and four open-label trials were included (n = 241). Results revealed a large effect of tDCS in the endpoint, but no significant effect between active and sham protocols. No predictor of response was found. EF analysis revealed that montages using the main electrode over the (pre)supplementary motor area with an extracephalic reference electrode might lead to stronger EFs in the predefined ROIs. Our results revealed that tDCS might be a promising intervention to treat OCD; however, larger studies are warranted.

Transcranial direct current stimulation (tDCS) in the management of epilepsy: A systematic review.

PURPOSE: Current therapies for the management of epilepsy are still suboptimal for several patients due to inefficacy, major adverse events, and unavailability. Transcranial direct current stimulation (tDCS), an emergent non-invasive neuromodulation technique, has been tested in epilepsy samples over the past two decades to reduce either seizure frequency or electroencephalogram (EEG) epileptiform discharges. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO record CRD42020160292). A thorough electronic search was completed in MEDLINE, EMBASE, CENTRAL and Scopus databases for trials that applied tDCS interventions to children and adults with epilepsy of any cause, from inception to April 30, 2020. RESULTS: Twenty-seven studies fulfilled eligibility criteria, including nine sham-controlled and 18 uncontrolled trials or case reports/series. Samples consisted mainly of drug-resistant focal epilepsy patients that received cathodal tDCS stimulation targeted at the site with maximal EEG abnormalities. At follow-up, 84 % (21/25) of the included studies reported a reduction in seizure frequency and in 43 % (6/14) a decline in EEG epileptiform discharge rate was observed. No serious adverse events were reported. CONCLUSIONS: Cathodal tDCS is both a safe and probably effective technique for seizure control in patients with drug-resistant focal epilepsy. However, published trials are heterogeneous regarding samples and methodology. More and larger sham-controlled randomized trials are needed, preferably with mechanistic informed stimulation protocols, to further advance tDCS therapy in the management of epilepsy.

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain.

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

Nonverbal behaviors are associated with increased vagal activity in major depressive disorder: Implications for the polyvagal theory.

BACKGROUND: Major depressive disorder (MDD) is associated with impairments in nonverbal behaviors (NVBs) and vagal activity. The polyvagal theory proposes that vagal activity regulates heart rate and NVBs by modulating a common anatomically and neurophysiologically discrete social engagement system. However, the association between these putative endophenotypes has not yet been explored. We hypothesize that in MDD, NVBs indicating positive affects and social interest and those indicating negative feelings and social disinterest could be associated with different patterns of vagal activity. METHODS: For this cross-sectional study we recruited 50 antidepressant-free participants with moderate-to-severe MDD. Vagal activity was indexed by heart rate variability (HRV) measures, and positive and negative nonverbal behaviors (NVBs) by a validated ethogram. Associations between NVBs and HRV were explored by bivariate analyses and multivariable models were adjusted by age, gender, depression severity, and self-reported positive and negative affects. RESULTS: HRV measures indicative of higher vagal activity were positively correlated with positive NVBs exhibited during the clinical interview. Conversely, NVBs related to negative affects, low energy and social disinterest were not associated with HRV. LIMITATIONS: Absence of a control group. CONCLUSIONS: The findings highlight that the examined depression endophenotypes (nonverbal behaviors and vagal activity) are related, shedding light on MDD pathophysiology in the context of the polyvagal theory.

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies. OBJECTIVE: To investigate the tolerability (rate of AEs) and acceptability (rate of dropouts) of tDCS. METHODS: Systematic review and meta-analysis of tDCS randomized, sham-controlled trials in healthy or neuropsychiatric adult samples from the first date available to March 9, 2016. We only included parallel studies performing at least 5 tDCS sessions. An adapted version of CONSORT guidelines for reporting harms outcomes was used to evaluate AE reporting. RESULTS: Sixty-four studies (2262 participants) were included. They had a low risk of publication bias and methodological bias for the items assessed. Dropout rates in active and sham tDCS groups were, respectively, 6% and 7.2% (OR = 0.82 [0.59-1.14]). However, almost half of studies reported no dropouts and only 23.4% reported its reasons; when reported, the most frequent reasons were AEs and protocol violation. A tolerability meta-analysis was not performed, as most studies did not report AEs. The quality of AEs reporting was also limited, particularly in smaller studies and stroke studies. CONCLUSIONS: Although overall dropout rate was low and similar in active and sham groups, studies did not adequately describe AEs. An updated questionnaire and guidelines for assessment of AEs in tDCS trials are proposed in order to standardize the reporting of AE in the field.