Resumo em Inglês:

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Resumo em Inglês:

Objectives: The objective of this study was to investigate the prevalence of the following risk behaviors: experimentation with cigarettes, electronic cigarettes, alcohol, substances, delinquent behavior, and sex at age 15, stratified by sex and socioeconomic position. We also investigated the prevalence of cigarette and alcohol experimentation at age 11 and the persistence and cumulative incidence of these behaviors between 11 and 15 years of age. Methods: In this cohort study, we included 3,491 11-year-olds and 1,949 15-year-olds from the 2004 Pelotas Birth Cohort. All outcomes were identified via confidential questionnaires and were analyzed as binary variables. Results: At age 11, there was a higher prevalence of cigarette experimentation among boys. At age 15, there was a higher prevalence of experimentation with alcohol, cigarettes, and substances among girls; experimentation with cigarettes and sex were more prevalent among those in a low socioeconomic position. We found a high cumulative incidence of alcohol experimentation, as well as persistent alcohol experimentation, in both boys and girls. Conclusions: Further research should clarify causal paths of the high prevalence of risk behaviors during adolescence and its increase among girls.

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Objective: Coronaviruses that cause respiratory infections in humans are known to be neuropathogenic. The purpose of this study is to determine whether there is an association between the severity of viral pneumonia and anxiety and depression levels in patients admitted to an intensive care unit (ICU) with coronavirus disease 2019 (COVID-19). Methods: Prospective study of 165 patients, patients were divided into two groups (intubated and non-intubated) according to whether they were intubated during follow-up. Results: Of 165 patients included, 70 were intubated after the first 7 days of follow-up. The Generalized Anxiety Disorder-7 (GAD-7) score was 10.37±3.75 (p < 0.001) in these patients. The length of ICU stay was 25±22.3 days (p < 0.001), and the length of overall hospital stay was 28.28±23.37 days, significantly longer than in patients who were not intubated (p < 0.001). The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment Score scores, as well as GAD-7 and Patient Health Questionnaire-9, were positively associated with length of ICU stay and length of hospital stay (p < 0.01). Conclusion: The presence and exacerbation of anxiety and depression symptoms can provide information about the aggravation and progression of the underlying disease.

Resumo em Inglês:

Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher among patients than controls. GCLC_GAG-7/9 genotype (OR = 4.3, 95%CI = 1.40-14.31, p = 0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR = 6.09, 95%CI = 1.93-22.59, p = 0.003) were found to be risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of patients with psychotic disorders, raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Resumo em Inglês:

Objective: Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. Methods: Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Resting-state positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. Results: Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). Conclusion: Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients.

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Objectives: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD. Methods: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing. Results: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and bvFTD did not differ regarding FER or mFP total scores, although patients with bvFTD had significantly higher difficulties than those in the BD1 group to detect social faux-pas (p < 0.001, d = 1.35). Conclusion: BD1 and bvFTD share deficits in the core SC functions. These findings should be considered in the development of tasks aiming to improve clinical differentiation between the two disorders.

Resumo em Inglês:

Currently, genome editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), are predominantly used to model genetic diseases. This genome editing system can correct point or frameshift mutations in risk genes. Here, we analyze and discuss the advantages of genome editing, its current applications, and the feasibility of the CRISPR/Cas9 system in research on psychiatric disorders. These disorders produce cognitive and behavioral alterations and their etiology is associated with polygenetic and environmental factors. CRISPR/Cas9 may reveal the biological mechanisms of psychiatric disorders at a basic research level, translating a suitable clinical approach for use in the diagnosis and treatment of psychiatric disorders. Genetic diagnosis and treatment for these disorders have not yet been fully established in psychiatry due to the limited understanding of their heterogeneity and polygenicity. We discuss the challenges and ethical issues in using CRISPR/Cas9 as a tool for diagnosis or gene therapy.

Resumo em Inglês:

Objectives: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). Results: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. Conclusion: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.

Resumo em Inglês:

Objectives: Religiosity and spirituality (R/S) have been negatively associated with several mental health problems, including delinquency. The study aimed to investigate the relationship between R/S and interpersonal violence using a systematic review. Methods: We conducted a descriptive systematic review followed by meta-analyses using seven different databases. We included observational studies that assessed the relationship between R/S and different types of interpersonal violence (physical and sexual aggression and domestic violence). Results: A total of 16,599 articles were screened in the databases and, after applying the eligibility criteria, 67 were included in the systematic review and 43 were included in the meta-analysis. The results showed that higher levels of R/S were significantly associated with decreased physical and sexual aggression, but not domestic violence. All selected studies evidenced sufficient methodological quality, with 26.8% being cohort studies. In the subanalyses, the role of R/S was more prevalent among adolescents. Conclusion: There is an inverse relationship between R/S and physical and sexual aggression, suggesting a protective role. However, these results were not observed for domestic violence. Healthcare professionals and managers should be aware of their patients’ beliefs when investigating interpersonal violence to create tailored interventions for reducing violent behavior.

Resumo em Inglês:

Objectives: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. Methods: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. Results: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. Conclusion: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.