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.

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.

The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies.

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

Ultrasound examination of the antrum to predict gastric content volume in the third trimester of pregnancy as assessed by MRI: A prospective cohort study.

BACKGROUND: Ultrasound examination of the gastric antrum allows reliable pre-operative assessment of gastric contents and volume in adult patients. However, during pregnancy, the change in the anatomical position of the stomach due to the gravid uterus leads to a change in the measured value of the antral area. Therefore, current mathematical models predicting gastric content volume (GCV) in the adult may not apply in term pregnant women. OBJECTIVE: To propose a mathematical model which is predictive of GCV in pregnant women and to assess the performance of an ultrasound qualitative grading scale (0 to 2) for the diagnosis of clear fluid volumes more than 0.8 and 1.5 ml kg. DESIGN: Prospective cohort study. SETTING: Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Lyon and Assistance Publique - Hôpitaux de Marseille, Hôpital Nord, Marseille, France. PATIENTS: Pregnant women in the third trimester of pregnancy. MAIN OUTCOME MEASURES: Comparison of the GCV as measured by MRI and the ultrasound measured antral cross-sectional area, and an assessment of gastric contents according to a 0 to 2 qualitative grading scale. RESULTS: Data from 34 women were analysed. A linear model predictive of GCV was constructed with a 95% agreement band of ±95 ml, with a mean polar angle of -8.7°. Performance of the qualitative grading scale to detect fluid volumes >0.8 and >1.5 ml kg was improved when used in a composite scale including a 505 mm antral area cut-off value in the semirecumbent supine position. CONCLUSION: We report a new mathematical model predictive of GCV in women in the third trimester of pregnancy. Furthermore, the combination of the qualitative and the quantitative ultrasound examination of the gastric antrum might be useful to assess gastric fluid volume in pregnant women. TRIAL REGISTRATION: ANSM Register N°2015-A00800-49.

NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings.

Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD). The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity. Recent data have demonstrated that NLRP3 activation appears to bridge the gap between immune activation and metabolic danger signals or stress exposure, which are key factors in the pathogenesis of psychiatric disorders. In this review, we discuss both preclinical and clinical evidence that links the assembly of the NLRP3 complex and the subsequent proteolysis and release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in chronic stress models and patients with MDD. Importantly, we also focus on the therapeutic potential of targeting the NLRP3 inflammasome complex to improve stress resilience and depressive symptoms.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

OBJECTIVES: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. METHODS: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. RESULTS: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. SIGNIFICANCE: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. METHODS: Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. KEY FINDINGS: Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. SIGNIFICANCE: Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE.

Variables associated with physical health-related quality of life in Parkinson's disease patients presenting for deep brain stimulation.

Deep brain stimulation (DBS) benefits Parkinson's disease (PD) patient's quality of life specially in domains as mobility, activities of daily living (ADL) and bodily discomfort (BD), but little is known about the variables associated with these HRQOL domains in patients presenting for DBS. The objective is to evaluate variables associated with of HRQOL in a Brazilian sample of PD patients presenting for DBS treatment, specifically in the domains related with motor symptoms. In a cross-sectional study of 59 PD patients evaluated at outpatient Unit for Movement Disorders, multiple linear regression analysis was performed to identify independent variables associated with mobility, ADL and BD domains of the 39-item Parkinson's disease questionnaire (PDQ-39). UPDRS III "on" scores, duration of the disease, age, presence of comorbidities and anxiety and depressive symptoms quantified by hospital anxiety and depression scale (HADS), were the independent variables. In our results, HADS scores were independently associated to mobility domain: ß coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: ß coefficient 1.57 (95 % CI 0.67-2.48). UPDRS III "on" scores were independently associated to mobility domain: 0.42 (95 % CI 0.03-0.81). The model of each multiple linear regression analysis explains 25 % of the mobility domain variability (p < 0.01) and 24 % of the BD domain variability (p < 0.01). Psychiatric symptoms were at least as relevant to quality of life as motor symptoms in PD patients presenting for DBS treatment. The effect of treating these psychiatric symptoms on patients' HRQOL deserves further investigation.

How predictable is the erectile function of patients with epilepsy?

INTRODUCTION: Erectile dysfunction (ED) is often reported by patients with epilepsy and may be related to endocrine system abnormalities, side effects of antiepileptic drugs, psychiatric comorbidities, and family or social difficulties. AIMS: This study aimed to identify independent predictor factors for ED in patients with epilepsy. MAIN OUTCOME MEASURES: the five-question form of the International Index of Erectile Function (IIEF-5). METHODS: Independent predictive factors for ED evaluated by the IIEF-5 questionnaire in 36 patients (mean age: 39 years) with focal epilepsy (mean: 6 seizures/month) were identified by multiple linear regression analysis. RESULTS: Eight (21.1%) patients were asymptomatic. Among the symptomatic patients, 11 (28.9%) had mild dysfunction, 10 (26.3%) had moderate dysfunction, and 9 (23.7%) showed severe ED. The multiple linear regression model including family income (B=0.005; p=0.05), education levels in years (B=0.54; p=0.03), depressive symptoms determined by HADS depression subscale (B=-0.49; p=0.03), and prolactin levels (B=-0.45; p=0.07) showed a moderate association (r=0.64) with the IIEF questionnaire and explained 41% (r(2)=0.41) of its variation. CONCLUSIONS: Erectile dysfunction is highly prevalent in patients with focal epilepsies. Education, depressive symptoms, and prolactin levels can predict erectile dysfunction in up to 41% of patients with epilepsy. This preliminary report justifies further efforts to make a large sample size study to identify independent biomarkers and therapeutic targets for ED treatment in patients with epilepsy.

Validation of diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy.

PURPOSE: This study aimed to evaluate the diagnostic accuracy of the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) as diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: One hundred three patients with drug-resistant MTLE-HS were enrolled. All patients underwent a neurological examination, interictal and ictal video-electroencephalogram (V-EEG) analyses, and magnetic resonance imaging (MRI). Psychiatric interviews were based on DSM-IV-TR criteria and ILAE Commission of Psychobiology classification as a gold standard; HRSD, BDI, HADS, and HADS-D were used as psychometric diagnostic tests, and receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores. RESULTS: For all the scales, the areas under the curve (AUCs) were approximately 0.8, and they were able to identify depression in this sample. A threshold of ≥9 on the HRSD and a threshold of ≥8 on the HADS-D showed a sensitivity of 70% and specificity of 80%. A threshold of ≥19 on the BDI and HADS-D total showed a sensitivity of 55% and a specificity of approximately 90%. The instruments showed a negative predictive value of approximately 87% and a positive predictive value of approximately 65% for the BDI and HADS total and approximately 60% for the HRSD and HADS-D. CONCLUSIONS: HRSD≥9 and HADS-D≥8 had the best balance between sensitivity (approximately 70%) and specificity (approximately 80%). However, with these thresholds, these diagnostic tests do not appear useful in identifying depressive disorder in this population with epilepsy, and their specificity (approximately 80%) and PPV (approximately 55%) were lower than those of the other scales. We believe that the BDI and HADS total are valid diagnostic tests for depressive disorder in patients with MTLE-HS, as both scales showed acceptable (though not high) specificity and PPV for this type of study.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.

INTRODUCTION: Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. METHODS: The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. RESULTS: At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. CONCLUSION: The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

The Revised Suicide Crisis Inventory (SCI-2): Factor Structure, Internal Consistency, and Validity in a Brazilian Sample.

OBJECTIVE: To examine the factor structure, reliability, and validity of the Brazilian version of the Suicide Crisis Inventory (SCI-2) among Brazilian adults. METHODS: The SCI-2 was cross-culturally adapted into Portuguese and administered to 2,265 individuals in the Brazilian community. Confirmatory factor analyses, internal consistency, and convergent and criterion validity against the suicidal narrative, stressful life events, suicidal ideation, and suicide attempts were examined. RESULTS: The revised one-factor model of the SCI-2 resulted in adequate, but not optimal, model fit (χ2[1539] = 31,442.79, p < .001, CFI = .99, TLI = .99, RMSEA = .09, SRMR = .05). The revised five-factor model, on the other hand, demonstrated good fit (χ2[1529] = 14,174.86, p < .001, CFI = 1.00, TLI = 1.00, RMSEA = .06, SRMR = .04). Comparison of these two models indicated that the five-factor exhibited a superior model fit to the one-factor model. The SCI-2 total and subscales showed strong internal consistency, good convergent, and criterion validity in relation to stressful life events, suicidal narrative (except goal disengagement subscale), suicidal ideation, and suicide attempts. CONCLUSIONS: These findings indicate that the Brazilian version of the SCI-2 is a valid tool for measuring symptoms of the Suicide Crisis Syndrome.

Abbreviated Suicidal Narrative Inventory: Factor Structure, Internal Consistency, and Validity in a Brazilian Sample.

AIM: To investigate the factor structure, reliability, and validity of the Brazilian version of the Abbreviated Suicidal Narrative Inventory (SNI-38). METHODS: We used an anonymous online questionnaire of the SNI-38 and self-report measures administered between November 2020 and October 2021 in the Brazilian community. Participants were recruited through social media advertisements. Confirmatory factor analysis was carried out to test the factor structure of the SNI-38. In addition, we examined internal consistency, and convergent validity against stressful life events, the suicide crisis syndrome, suicidal ideation, and suicide attempts. RESULTS: 2660 participants were included. The eight-factor model SNI-38 had a good model fit (χ2[637] = 7,473.98, p < .001, CFI = .99, TLI = .99, RMSEA = .07, SRMR = .06); all items were significantly and positively loaded onto their respective factors (factor loadings ≥ .45). Reliability was good to high in all subscales except goal disengagement. Additionally, all subscales - except goal disengagement - were correlated positively which the suicide crisis syndrome, stressful life events, lifetime/past-month suicidal ideation, and lifetime suicide attempts. CONCLUSIONS: These findings provide preliminary support for the validity of the Brazilian version of the SNI-38, being an appropriate and valid tool for measuring suicidal narrative among Brazilian samples.

Social support and suicidality during the COVID-19 pandemic among Brazilian healthcare workers: a longitudinal assessment of an online repeated cross-sectional survey.

INTRODUCTION: Healthcare workers (HCWs) are at an increased risk of suicide compared to non-healthcare workers. This study aims to investigate the association between social support and suicidal ideation and behavior (SIB) during the COVID-19 pandemic among Brazilian HCWs. METHODS: This study utilizes data from 10,885 participants who answered the first (time point 1 - between May and June of 2020) and second (time point 2 - between December 2020 and February 2021) assessments of an online repeated cross-sectional survey for evaluating mental health and quality of life of HCWs during the COVID-19 pandemic in Brazil. Logistic regression analysis was conducted to investigate the relationship between social support as the independent variable (time point 1) and SIB as the outcomes (time point 2). RESULTS: Higher social support was associated with a significantly lower chance of reporting SIB in the month prior to follow-up assessment (adjusted odds ratio [AOR]: 0.71, CI 95% 0.66 - 0.76 and AOR 0.61, CI 95% 0.54 - 0.68, respectively). These associations were independent of sex, age, feelings of loneliness, and self-reported psychiatric disorders. CONCLUSION: Social support is associated with a lower chance of suicidality among HCWs, a protective role that is probably more evident for suicidal behavior.

Non-Invasive Neuromodulation Methods to Alleviate Symptoms of Huntington's Disease: A Systematic Review of the Literature.

Huntington's disease (HD) is a progressive and debilitating neurodegenerative disease. There is growing evidence for non-invasive neuromodulation tools as therapeutic strategies in neurodegenerative diseases. This systematic review aims to investigate the effectiveness of noninvasive neuromodulation in HD-associated motor, cognitive, and behavioral symptoms. A comprehensive literature search was conducted in Ovid MEDLINE, Cochrane Central Register of Clinical Trials, Embase, and PsycINFO from inception to 13 July 2021. Case reports, case series, and clinical trials were included while screening/diagnostic tests involving non-invasive neuromodulation, review papers, experimental studies on animal models, other systematic reviews, and meta-analyses were excluded. We have identified 19 studies in the literature investigating the use of ECT, TMS, and tDCS in the treatment of HD. Quality assessments were performed using Joanna Briggs Institute's (JBI's) critical appraisal tools. Eighteen studies showed improvement of HD symptoms, but the results were very heterogeneous considering different intervention techniques and protocols, and domains of symptoms. The most noticeable improvement involved depression and psychosis after ECT protocols. The impact on cognitive and motor symptoms is more controversial. Further investigations are required to determine the therapeutic role of distinct neuromodulation techniques for HD-related symptoms.

Longitudinal profile of post-traumatic symptoms in HealthCare Workers during COVID-19 pandemic: A latent transition model.

INTRODUCTION: Pandemics have the potential to be considered traumatic event, increasing the risk of developing post-traumatic stress symptoms (PTSS) in HealthCare Workers (HCW). However, few longitudinal studies have evaluated the impact of prolonged exposure to the risk imposed by COVID-19. Our aim was to identify subgroups of HCW with profiles of PTSS, how this profile changed during the pandemic and which variables were related to these changes. METHODS: We evaluated the levels of PTSS and psychological distress in a Brazilian HealthCare Workers' sample (n = 1398) in three waves of assessment: from May to June 2020 (Wave 1), December 2020 to February 2021 (Wave 2) and May to August 2021 (Wave 3), using Latent Profile Analysis (LPA) to identify subgroups with different profiles of symptms, and then, Latent Transition Analysis (LTA) was applied to examine changes in symptom profiles over time, including gender, psychiatric diagnosis history, and pandemic-related fears as covariates. RESULTS: two profiles were identified: high-PTSS profile (Wave 1-23%; Wave 2-64% and Wave 3-73%) and a low-PTSS (Wave 1-77%; Wave 2-36% and Wave 3-27%). Being female, fear of contamination, and fearing financial problems were strong predictors of changes in the profile. In addition, the participants had a high probability of being in the high-PTSS in the long run. CONCLUSION: These results suggests that targeted interventions can mitigate the impact of pandemic. Providing financial support, and psychological support can be beneficial for those with psychiatric diagnoses and experiencing bereavement.

Processing speed - A potential candidate cognitive endophenotype for bipolar disorder.

Background: Bipolar disorder (BD) is a chronic multifactorial disorder that presents with cognitive impairment as one of its main features, in patients as well as in their first-degree relatives. However, the profile of cognitive dysfunction in BD patients and their relatives is not yet well defined. Various neurocognitive deficits have been proposed as endophenotypes for BD. In the present study, we explored the susceptibility to neurocognitive deficits in BD patients and their siblings compared to healthy controls. Method: A sample consisting of patients diagnosed with BD (N=37), their unaffected siblings (N=30) and a healthy control group (N=39) was assessed using the Brief Assessment of Cognition for Affective Disorders (BAC-A) battery of tests in various cognitive domains: memory, processing speed, working memory, reasoning and problem solving, and affective processing. Results: Compared to healthy controls, BD patients and their unaffected siblings showed deficits in attention and motor speed, or processing speed as measured by the Symbol coding task (p = 0.008), as well as a similar degree of impairment (p = 1.000). Limitations: The lack of statistically significant findings in the other cognitive domains could be related to differences in task difficulty. Most patients were taking psychotropic medication with varying effects on cognition and being treated as outpatients, implying a currently higher level of functioning, which may limit extrapolation of the sample to the general population of BD patients. Conclusions: These results support the view of considering processing speed as an endophenotype for bipolar disorder.

Impacts of mental health in the sleep pattern of healthcare professionals during the COVID-19 pandemic in Brazil.

BACKGROUND: After >2 years of the Coronavirus Disease-19 (COVID-19) pandemic, it is well established how sleep symptoms are rising, especially among healthcare workers (HCW). The aim of this study is to evaluate what features are associated with sleep disturbances in the HCW population. METHODS: Cross-sectional and longitudinal analysis of social and clinical variables associated with sleep problems and insomnia incidence in HCW in a large, national-level cohort. The measurement of sleep problems was assessed by self-report using Jenkins Sleep Scale (JSS). A multivariate analysis was used in the cross-sectional design and generalized linear models were used in the longitudinal design. RESULTS: 10,467 HCW were analyzed in the cross-sectional analysis, 3313 participants were analyzed in the three timepoints of the study. Sex, previously diagnosed mental illness and frontline work with COVID-19 were associated with higher scores in JSS in the univariate analysis. In the multivariate analysis, only previous diagnosis of mental illness was related with sleep difficulties, especially previously diagnosed insomnia. The longitudinal analysis concluded that previous diagnosis of mental illnesses was associated with higher levels of insomnia development (OR = 11.62). The self-reported disorders found to be major risk factors were addiction (OR = 7.69), generalized anxiety disorder (OR = 3.67), social anxiety (OR = 2.21) and bipolar disorder (OR = 2.21). LIMITATIONS: Attrition bias. CONCLUSIONS: Previous diagnosis of mental illness was strongly related to insomnia development in HCW during the COVID-19 pandemic. Strategies that focus on this population are advised.

Decision-making styles during stressful scenarios: The role of anxiety in COVID-19 pandemic.

Introduction: Decision-making is not purely rational but highlighted by the influence of intuitive and emotional processes. Recently, researchers have focused more attention on understanding which environmental and personal features influence decision-making processes, and how. Objective and methods: On this study, we investigate whether Trait Anxiety moderates the impact of Post-Traumatic Stress (PTS) symptoms reported during COVID-19 pandemic on decision-making styles. Results: The study included 1,358 Brazilian participants (80% women) aged between 20 and 74 (M = 41.11; SD = 11.23) who responded to an online survey between May and August of the year 2021 of COVID-19 pandemic to The State-Trait Anxiety Inventory, The Decisions Styles Scale, The Impact of Event Scale - Revised and questions related to COVID-19. Through moderation analysis, we observed that experiencing PTS is associated with a higher tendency to biased/heuristic decision-making processes. Discussion: Trait Anxiety seems to influence how people respond to PTS symptoms on decision-making related processes. Subjects with higher Trait Anxiety reported lower tendency to appeal to rationality, especially under higher reported levels of PTS. Meanwhile, lower Trait Anxiety subjects exhibited more reason-based decision-making under higher rates of PTS. This work contributes to a deeper understanding of the interplay among environmental and individual differences on decision-making styles and helps to identify factors of vulnerability for poorer cognitive functioning on stressful scenarios.

Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder.

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.