White matter predicts tDCS antidepressant effects in a sham-controlled clinical trial study.

Transcranial direct current stimulation (tDCS) has been used as treatment for depression, but its effects are heterogeneous. We investigated, in a subsample of the clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECTTDCS), whether white matter areas associated with depression disorder were associated with tDCS response. Baseline diffusion tensor imaging data were analyzed from 49 patients (34 females, mean age 41.9) randomized to escitalopram 20 mg/day, tDCS (2 mA, 30 min, 22 sessions), or placebo. Antidepressant outcomes were assessed by Hamilton Depression Rating Scale-17 (HDRS) after 10-week treatment. We used whole-brain tractography for extracting white matter measures for anterior corpus callosum, and bilaterally for cingulum bundle, striato-frontal, inferior occipito-frontal fasciculus and uncinate. For the rostral body, tDCS group showed higher MD associated with antidepressant effects (estimate = -5.13 ± 1.64, p = 0.002), and tDCS significantly differed from the placebo and the escitalopram group. The left striato-frontal tract showed higher FA associated with antidepressant effects (estimate = -2.14 ± 0.72, p = 0.003), and tDCS differed only from the placebo group. For the right uncinate, the tDCS group lower AD values were associated with higher HDRS decrease (estimate = -1.45 ± 0.67, p = 0.031). Abnormalities in white matter MDD-related areas are associated with tDCS antidepressant effects. Suggested better white matter microstructure of the left prefrontal cortex was associated with tDCS antidepressant effects. Future studies should investigate whether these findings are driven by electric field diffusion and density in these areas.

Social cognition and suicide-related behaviors in depression: a cross-sectional, exploratory study

Objective: To explore the association between social cognition and previous suicide attempts and non-suicidal self-injurious behavior in adults with unipolar depressive disorders. Methods: Seventy-two patients undergoing outpatient treatment for unipolar depression were enrolled in this cross-sectional study. Theory of mind was assessed using the Hinting Task and the Revised Reading the Mind in the Eyes Test. Empathy was evaluated using the Interpersonal Reactivity Index. Lifetime suicide attempts and non-suicidal self-injurious behavior were assessed using the Columbia Suicide Risk Rating Scale. Participants with and without these suicide-related outcomes were compared in terms of social cognition. Results: Patients with previous suicide attempts performed worse on the Reading the Mind in the Eyes Test (p = 0.017). Patients with a history of non-suicidal self-injurious behavior were younger (p = 0.005), had a younger age at first depressive episode (p = 0.017), and scored higher on personal distress in the Interpersonal Reactivity Index (p = 0.027). Only personal distress remained independently associated with non-suicidal self-injurious behavior in multivariable analysis (p = 0.038). Conclusion: Among patients with depression, those with previous suicide attempts or non-suicidal self-injurious behavior showed worse social cognition. These results encourage future research on social cognition deficits as clinical markers of suicide-related behaviors and as targets for interventions.

A narrative review on invasive brain stimulation for treatment-resistant depression

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Emotional Stability and Anxiety Symptoms Differentiates People Leaving the Home Usually During the Covid-19 Pandemic.

Objective: The population's adhesion to measures to ensure social distancing represents a great management challenge in a pandemic context. Despite of evidence shown that social distancing is effective, lack of adherence still persists in many countries. Therefore, it is challenging to separate the effectiveness of government measures, from social distancing driven by personal initiatives. Theory: It is possible that the output of protective behaviors, such as adherence to protective measures and staying in social isolation, is influenced by individual characteristics, such as personality traits or symptoms of mental distress of anxiogenic nature. We hypothesized that individuals with more expressive symptoms of fear or anxiety would have a more protective behavioral tendency in terms of risk exposure, leaving less home during the pandemic. In contrast, individuals with greater emotional stability, as they feel more secure and with a lower perception of risk, could go out more often. Method: A total of 2709 individuals from all regions of Brazil participated in the study (mean age = 42 years; 2134 women). Correlation analysis was performed to investigate the relationships between personality traits according to the big five model and Psychopathological Symptoms (BSI). Then, correlation analysis was performed to investigate how people that go out often differ from people that stay at home, in both symptoms and personality traits. Finally, to investigate the predictors for going out usually, we use multiple regression analysis, using gender, marital status, level of education, and personality traits. Results: During the second wave of COVID-19 in Brazil, individuals with higher emotional stability tended to leave home more than those with more expressive levels of anxiogenic dysregulation. These results reinforce the role of both personality traits and psychopathological symptoms in prophylactic behavior during COVID-19 pandemics. Conclusions: Individuals with greater emotional stability were more likely to leave home during the second wave of COVID-19 than those with higher levels of anxiogenic dysregulation.

Treatment-resistant bipolar depression: concepts and challenges for novel interventions

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.

Social cognition and suicide-related behaviors in depression: a cross-sectional, exploratory study.

OBJECTIVE: To explore the association between social cognition and previous suicide attempts and non-suicidal self-injurious behavior in adults with unipolar depressive disorders. METHODS: Seventy-two patients undergoing outpatient treatment for unipolar depression were enrolled in this cross-sectional study. Theory of mind was assessed using the Hinting Task and the Revised Reading the Mind in the Eyes Test. Empathy was evaluated using the Interpersonal Reactivity Index. Lifetime suicide attempts and non-suicidal self-injurious behavior were assessed using the Columbia Suicide Risk Rating Scale. Participants with and without these suicide-related outcomes were compared in terms of social cognition. RESULTS: Patients with previous suicide attempts performed worse on the Reading the Mind in the Eyes Test (p = 0.017). Patients with a history of non-suicidal self-injurious behavior were younger (p = 0.005), had a younger age at first depressive episode (p = 0.017), and scored higher on personal distress in the Interpersonal Reactivity Index (p = 0.027). Only personal distress remained independently associated with non-suicidal self-injurious behavior in multivariable analysis (p = 0.038). CONCLUSION: Among patients with depression, those with previous suicide attempts or non-suicidal self-injurious behavior showed worse social cognition. These results encourage future research on social cognition deficits as clinical markers of suicide-related behaviors and as targets for interventions.

Treatment-resistant bipolar depression: concepts and challenges for novel interventions.

Treatment-resistant bipolar depression (TRBD) has been reported in about one-quarter of patients with bipolar disorders, and few interventions have shown clear and established effectiveness. We conducted a narrative review of the published medical literature to identify papers discussing treatment-resistant depression concepts and novel interventions for bipolar depression that focus on TRBD. We searched for potentially relevant English-language articles published in the last decade. Selected articles (based on the title and abstract) were retrieved for a more detailed evaluation. A number of promising new interventions, both pharmacological and non-pharmacological, are being investigated for TRBD treatment, including ketamine, lurasidone, D-cycloserine, pioglitazone, N-acetylcysteine, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, cyclooxygenase 2 inhibitors, magnetic seizure therapy, intermittent theta-burst stimulation, deep transcranial magnetic stimulation, vagus nerve stimulation therapy, and deep brain stimulation. Although there is no consensus about the concept of TRBD, better clarification of the neurobiology associated with treatment non-response could help identify novel strategies. More research is warranted, mainly focusing on personalizing current treatments to optimize response and remission rates.

A narrative review on invasive brain stimulation for treatment-resistant depression.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Dysregulation of mitochondrial dynamics, mitophagy and apoptosis in major depressive disorder: Does inflammation play a role?

Recent studies have suggested that mitochondrial dysfunction and dysregulated neuroinflammatory pathways are involved in the pathophysiology of major depressive disorder (MDD). Here, we aimed to assess the differences in markers of mitochondrial dynamics, mitophagy, general autophagy, and apoptosis in peripheral blood mononuclear cells (PBMCs) of MDD patients (n = 77) and healthy controls (HCs, n = 24). Moreover, we studied inflammation engagement as a moderator of mitochondria dysfunctions on the severity of depressive symptoms. We found increased levels of Mfn-2 (p < 0.001), short Opa-1 (S-Opa-1) (p < 0.001) and Fis-1 (p < 0.001) in MDD patients, suggesting an increase in the mitochondrial fragmentation. We also found that MDD patients had higher levels of Pink-1 (p < 0.001), p62/SQSTM1 (p < 0.001), LC3B (p = 0.002), and caspase-3 active (p = 0.001), and lower levels of parkin (p < 0.001) compared with HCs. Moreover, we showed that that MDD patients with higher CRP levels had higher levels of Mfn-2 (p = 0.001) and LC3B (p = 0.002) when compared with MDD patients with low CRP. Another notable finding was that the severity of depressive symptoms in MDD is associated with changes in protein levels in pathways related to mitochondrial dynamics and mitophagy, and can be dependent on the inflammatory status. Overall, our study demonstrated that a disruption in the mitochondrial dynamics network could initiate a cascade of abnormal changes relevant to the critical pathological changes during the course of MDD and lead to poor outcomes.

Cross-cultural adaptation and psychometric evaluation of the Brazilian version of the Temporal Experience of Pleasure Scale (TEPS-Br).

INTRODUCTION: Anhedonia is a critical symptom of major depressive disorder that is defined as the reduced ability to experience pleasure. The Temporal Experience of Pleasure Scale (TEPS) is commonly used to measure anhedonia and has exhibited satisfactory reliability. OBJECTIVES: We aim to perform cross-cultural adaptation of a Brazilian version of the TEPS and evaluate its psychometric properties. METHOD: The cross-cultural adaptation was performed according to previously established protocols. Cronbach's alpha coefficient of internal consistency was used to establish the degree of interrelation and coherence of items. Also, we calculated the intraclass correlation coefficient to determine the stability of the scale after a proposed interval had elapsed and used exploratory factor analysis to evaluate the scale's factor structure and content validity. Principal component analysis was used to determine the factors to be retained in the factor model. RESULTS: The participants reported that the Brazilian version of the TEPS had good comprehensibility and applicability. The results revealed a statistically significant correlation between measures. The intraclass correlation coefficient calculated was significant. The Cronbach's alpha value calculated indicated that the scale's overall internal consistency was adequate. CONCLUSION: The Portuguese version of the TEPS scale proposed achieved good comprehensibility for the Brazilian population and its psychometric characteristics demonstrated good reliability and validity.

Cross-cultural adaptation and psychometric evaluation of the Brazilian version of the Temporal Experience of Pleasure Scale (TEPS-Br)

Abstract Introduction: Anhedonia is a critical symptom of major depressive disorder that is defined as the reduced ability to experience pleasure. The Temporal Experience of Pleasure Scale (TEPS) is commonly used to measure anhedonia and has exhibited satisfactory reliability. Objectives: We aim to perform cross-cultural adaptation of a Brazilian version of the TEPS and evaluate its psychometric properties. Method: The cross-cultural adaptation was performed according to previously established protocols. Cronbach's alpha coefficient of internal consistency was used to establish the degree of interrelation and coherence of items. Also, we calculated the intraclass correlation coefficient to determine the stability of the scale after a proposed interval had elapsed and used exploratory factor analysis to evaluate the scale's factor structure and content validity. Principal component analysis was used to determine the factors to be retained in the factor model. Results: The participants reported that the Brazilian version of the TEPS had good comprehensibility and applicability. The results revealed a statistically significant correlation between measures. The intraclass correlation coefficient calculated was significant. The Cronbach's alpha value calculated indicated that the scale's overall internal consistency was adequate. Conclusion: The Portuguese version of the TEPS scale proposed achieved good comprehensibility for the Brazilian population and its psychometric characteristics demonstrated good reliability and validity.

Brazilian Psychiatric Association guidelines for the management of suicidal behavior. Part 2. Screening, intervention, and prevention

This article continues our presentation of the Brazilian Psychiatric Association guidelines for the management of patients with suicidal behavior, with a focus on screening, intervention, postvention, prevention, and promotion. For the development of these guidelines, we conducted a systematic review of the MEDLINE (via PubMed), Cochrane Database of Systematic Reviews, Web of Science, and SciELO databases for research published from 1997 to 2020. Systematic reviews, clinical trials, and cohort/observational studies on screening, intervention, and prevention in suicidal behavior were included. This project involved 14 Brazilian psychiatry professionals and 1 psychologist selected by the Psychiatric Emergencies Committee of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. Publications were evaluated according to the 2011 Oxford Center for Evidence-Based Medicine (OCEBM) Levels of Evidence Classification. Eighty-five articles were reviewed (of 5,362 initially collected and 755 abstracts on the drug approach). Forms of screening, intervention, and prevention are presented. The intervention section presents evidence for psychotherapeutic and drug interventions. For the latter, it is important to remember that each medication is effective only for specific groups and should not replace treatment protocols. We maintain our recommendation for the use of universal screening plus intervention. Although the various studies differ in terms of the populations evaluated and several proposals are presented, there is already significant evidence for certain interventions. Suicidal behavior can be analyzed by evidence-based medicine protocols. Currently, the best strategy is to combine several techniques through the Safety Plan. Nevertheless, further research on the topic is needed to elucidate some approaches with particular potential for intervention and prevention. Systematic review registry number: CRD42020206517

Brazilian Psychiatric Association guidelines for the management of suicidal behavior. Part 1. Risk factors, protective factors, and assessment

Suicide is a global public health problem that causes the loss of more than 800,000 lives each year, principally among young people. In Brazil, the average mortality rate attributable to suicide is approximately 5.23 per 100,000 population. Although many guidelines have been published for the management of suicidal behavior, to date, there are no recent guidelines based on the principles of evidence-based medicine that apply to the reality of suicide in Brazil. The objective of this work is to provide key guidelines for managing patients with suicidal behavior in Brazil. This project involved 11 Brazilian psychiatry professionals selected by the Psychiatric Emergencies Committee (Comissão de Emergências Psiquiátricas) of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. For the development of these guidelines, 79 articles were reviewed (from 5,362 initially collected and 755 abstracts). In this review, we present definitions, risk and protective factors, assessments, and an introduction to the Safety Plan. Systematic review registry number: CRD42020206517

Stigma toward individuals with mental disorders among Brazilian psychiatrists: a latent class analysis

Objective: The stigma toward individuals with mental disorders is highly prevalent, not only in the general population but among health care providers as well. The aim of this study was to identify subgroups based on stigmatizing beliefs related to psychiatric disorders among Brazilian psychiatrists, as well as to investigate their association with clinical and personality characteristics. Methods: Latent cluster analysis was used to find subgroups of cases in multivariate data according to a psychotic (schizophrenia) and a nonpsychotic disorder (attention-deficit hyperactivity disorder). The clusters for each psychiatric disorder were compared according to sociodemographic, emotional traits, and personality characteristics. Results: A total of 779 psychiatrists answered the questionnaire. Three different subgroups of stigma levels were identified regarding schizophrenia: the highest (n=202 [51.7%]), intermediate (108 [27.6%]), and the lowest (81 [20.7%]). Participants from the highest stigma group had a significantly longer time since graduation, higher anxiety-state scores, and lower positive affect. Two subgroups were identified with respect to attention-deficit hyperactivity disorder, although there were no differences between them in sociodemographic or clinical variables. Conclusion: There were more subgroups of stigmatizing beliefs regarding psychotic disorders. Individual characteristics, such as those related to trait anxiety and affect, can be associated with high stigma toward schizophrenia.

Neurobiology of COVID-19: how can the virus affect the brain?

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which has been declared a public health emergency of international interest, with confirmed cases in most countries. COVID-19 presents manifestations that can range from asymptomatic or mild infections up to severe manifestations that lead to hospitalization and death. A growing amount of evidence indicates that the virus may cause neuroinvasion. Postmortem brain study findings have included edema, hemorrhage, hydrocephalus, atrophy, encephalitis, infarcts, swollen axons, myelin loss, gliosis, neuronal satellitosis, hypoxic-ischemic damage, arteriolosclerosis, leptomeningeal inflammation, neuronal loss, and axon degeneration. In addition, the COVID-19 pandemic is causing dangerous effects on the mental health of the world population, some of which can be attributed to its social impact (social distancing, financial issues, and quarantine). There is also a concern that environmental stressors, enhanced by psychological factors, are contributing to the emergence of psychiatric outcomes during the pandemic. Although clinical studies and diagnosing SARS-CoV-2-related neurological disease can be challenging, they are necessary to help define the manifestations and burden of COVID-19 in neurological and psychiatric symptoms during and after the pandemic. This review aims to present the neurobiology of coronavirus and postmortem neuropathological hallmarks.

Brazilian Psychiatric Association guidelines for the management of suicidal behavior. Part 1. Risk factors, protective factors, and assessment.

Suicide is a global public health problem that causes the loss of more than 800,000 lives each year, principally among young people. In Brazil, the average mortality rate attributable to suicide is approximately 5.23 per 100,000 population. Although many guidelines have been published for the management of suicidal behavior, to date, there are no recent guidelines based on the principles of evidence-based medicine that apply to the reality of suicide in Brazil. The objective of this work is to provide key guidelines for managing patients with suicidal behavior in Brazil. This project involved 11 Brazilian psychiatry professionals selected by the Psychiatric Emergencies Committee (Comissão de Emergências Psiquiátricas) of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. For the development of these guidelines, 79 articles were reviewed (from 5,362 initially collected and 755 abstracts). In this review, we present definitions, risk and protective factors, assessments, and an introduction to the Safety Plan. Systematic review registry number: CRD42020206517.

Stigma toward individuals with mental disorders among Brazilian psychiatrists: a latent class analysis.

OBJECTIVE: The stigma toward individuals with mental disorders is highly prevalent, not only in the general population but among health care providers as well. The aim of this study was to identify subgroups based on stigmatizing beliefs related to psychiatric disorders among Brazilian psychiatrists, as well as to investigate their association with clinical and personality characteristics. METHODS: Latent cluster analysis was used to find subgroups of cases in multivariate data according to a psychotic (schizophrenia) and a nonpsychotic disorder (attention-deficit hyperactivity disorder). The clusters for each psychiatric disorder were compared according to sociodemographic, emotional traits, and personality characteristics. RESULTS: A total of 779 psychiatrists answered the questionnaire. Three different subgroups of stigma levels were identified regarding schizophrenia: the highest (n=202 [51.7%]), intermediate (108 [27.6%]), and the lowest (81 [20.7%]). Participants from the highest stigma group had a significantly longer time since graduation, higher anxiety-state scores, and lower positive affect. Two subgroups were identified with respect to attention-deficit hyperactivity disorder, although there were no differences between them in sociodemographic or clinical variables. CONCLUSION: There were more subgroups of stigmatizing beliefs regarding psychotic disorders. Individual characteristics, such as those related to trait anxiety and affect, can be associated with high stigma toward schizophrenia.

Brazilian Psychiatric Association guidelines for the management of suicidal behavior. Part 2. Screening, intervention, and prevention.

This article continues our presentation of the Brazilian Psychiatric Association guidelines for the management of patients with suicidal behavior, with a focus on screening, intervention, postvention, prevention, and promotion. For the development of these guidelines, we conducted a systematic review of the MEDLINE (via PubMed), Cochrane Database of Systematic Reviews, Web of Science, and SciELO databases for research published from 1997 to 2020. Systematic reviews, clinical trials, and cohort/observational studies on screening, intervention, and prevention in suicidal behavior were included. This project involved 14 Brazilian psychiatry professionals and 1 psychologist selected by the Psychiatric Emergencies Committee of the Brazilian Psychiatric Association for their experience and knowledge in psychiatry and psychiatric emergencies. Publications were evaluated according to the 2011 Oxford Center for Evidence-Based Medicine (OCEBM) Levels of Evidence Classification. Eighty-five articles were reviewed (of 5,362 initially collected and 755 abstracts on the drug approach). Forms of screening, intervention, and prevention are presented. The intervention section presents evidence for psychotherapeutic and drug interventions. For the latter, it is important to remember that each medication is effective only for specific groups and should not replace treatment protocols. We maintain our recommendation for the use of universal screening plus intervention. Although the various studies differ in terms of the populations evaluated and several proposals are presented, there is already significant evidence for certain interventions. Suicidal behavior can be analyzed by evidence-based medicine protocols. Currently, the best strategy is to combine several techniques through the Safety Plan. Nevertheless, further research on the topic is needed to elucidate some approaches with particular potential for intervention and prevention. Systematic review registry number: CRD42020206517.