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This study aims to compare the serum cytokine levels between controls, individuals with a current depressive episode (CDE) with childhood trauma and individuals with CDE without childhood trauma. This is a cross-sectional with paired sample nested in a population-based study. For the purposes of the current study, subjects who had psychotic symptoms, generalized anxiety disorder, and who refused to perform blood collection were excluded. Subsequently, only individuals who had a current depressive episode were selected (n = 76). Another 76 subjects were randomly paired by sex and age, constituting a population control group. The measurements of serum cytokine levels were performed using the multiplex analysis method. In the group with a CDE, when compared to the population control group, the following cytokines were high: IL-1β, IL-2, IL-4, IL-6, IL-17A, IFN-γ and TNF-α (p 0.05). On the other hand, there was a decrease in the levels of cytokines IL-10 (p = 0.027) and IL12p70 (p = 0.001). Bonferroni test demonstrates that there is no statistically significant difference in serum cytokine levels between subjects with a CDE, with and without trauma (p 0.05). In a multivariable logistic regression, adjusting for socioeconomic status, tobacco, alcohol and illicit drugs abuse/dependence, and use of psychiatric medication, we found that cytokines serum levels remained associated with CDE even when adjusted for these potential confounders. Our findings demonstrate that monitoring cytokine levels and immune function may be beneficial in preventing the development of a CDE. However, future research is necessary to investigate the impact of trauma on the relationship between inflammation and CDE.

Frontotemporal dementia and amyotrophic lateral sclerosis (FTD-ALS) are associated with both a repeat expansion in the C9orf72 gene and mutations in the TANK-binding kinase 1 ( TBK1 ) gene. We found that TBK1 is phosphorylated in response to C9orf72 poly(Gly-Ala) [poly(GA)] aggregation and sequestered into inclusions, which leads to a loss of TBK1 activity and contributes to neurodegeneration. When we reduced TBK1 activity using a TBK1-R228H (Arg 228 →His) mutation in mice, poly(GA)-induced phenotypes were exacerbated. These phenotypes included an increase in TAR DNA binding protein 43 (TDP-43) pathology and the accumulation of defective endosomes in poly(GA)-positive neurons. Inhibiting the endosomal pathway induced TDP-43 aggregation, which highlights the importance of this pathway and TBK1 activity in pathogenesis. This interplay between C9orf72 , TBK1 , and TDP-43 connects three different facets of FTD-ALS into one coherent pathway.

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18-35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737-rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes.

This study aimed to develop a classification model predicting incident bipolar disorder (BD) cases in young adults within a 5-year interval, using sociodemographic and clinical features from a large cohort study. We analyzed 1,091 individuals without BD, aged 18 to 24 years at baseline, and used the XGBoost algorithm with feature selection and oversampling methods. Forty-nine individuals (4.49%) received a BD diagnosis five years later. The best model had an acceptable performance (test AUC: 0.786, 95% CI: 0.686, 0.887) and included ten features: feeling of worthlessness, sadness, current depressive episode, selfreported stress, self-confidence, lifetime cocaine use, socioeconomic status, sex frequency, romantic relationship, and tachylalia. We performed a permutation test with 10,000 permutations that showed the AUC from the built model is significantly better than random classifiers. The results provide insights into BD as a latent phenomenon, as depression is its typical initial manifestation. Future studies could monitor subjects during other developmental stages and investigate risk populations to improve BD characterization. Furthermore, the usage of digital health data, biological, and neuropsychological information and also neuroimaging can help in the rise of new predictive models.

We investigated whether women diagnosed with comorbid bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) experience higher disruptions in biological rhythms in two independent study samples. The first study has a population-based sample of 727 women, including 104 women with PMDD only, 43 women with BD only, 24 women with comorbid PMDD and BD, and 556 women without BD or PMDD (controls). Biological rhythm disruptions were cross-sectionally evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). The second study enrolled 77 outpatient women who completed prospective assessments at two timepoints: during the mid-follicular and the late-luteal phases of their menstrual cycles, using the BRIAN, and included 19 women with PMDD, 16 with BD, 17 with comorbid PMDD and BD, and 25 controls. In the population-based sample, all the diagnostic groups (BD, PMDD, BDPMDD) presented greater biological rhythm disruption than controls. In addition, women with BD presented greater overall biological rhythms disruption, and greater disruption in sleep, activity, and eating patterns, than women with PMDD. In the outpatient sample study, women with BDPMDD showed greater disruption in the social domain than women with PMDD. In the outpatient sample, women with BDPMDD reported significantly higher disruptions in biological rhythms across both the follicular and the luteal phases of the menstrual cycle. The comorbidity between BD and PMDD may affect biological rhythms beyond the luteal phase of the menstrual cycle. These results support previous literature on the increased illness burden of women diagnosed with comorbid BD and PMDD.

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord1. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing2–4. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies5,6, but how those variants increase risk for disease is unknown. Here we show that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harbouring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function.

Objective: to assess the association between caregivers’ mental disorders and schoolchildren’s obesogenic eating behavior. Methods: cross-sectional study used a public school-based sample of children and their primary caregivers. Caregivers had to report depressive episodes or generalized anxiety disorder (GAD) during the Mini-International Neuropsychiatric Interview (MINI). Children’s obesogenic eating behavior were assessed using food responsiveness (FR) and emotional overeating (EOE) subscales of the Children’s Eating Behaviour Questionnaire (CEBQ). Bivariate analysis was conducted using the t-test, ANOVA, Pearson correlation, and adjusted linear regression model was used (including variables caregivers: sex, age, economic indicator, and schooling; schoolchildren: sex and nutritional status). Results: study includes 596 children-caregiver dyads (309 boys and 287 girls). Among caregivers, 24.7% had experienced current depressive episodes, 38.7% had past depressive episodes, and 17.2% had GAD. We observed, after adjusted analysis, that having a caregiver in a current depressive episode, increases schoolchildren’s obesogenic behavior of, for FR at 0.235 points (β=0.235; CI95%=0.022-0.449;) and EOE at 0.337 points (β=0.337; CI95%=0.162-0.512). Conclusion: caregivers’ current depressive episodes were associated with higher averages of obesogenic eating behavior (caregiver-reported), both in consuming palatable food without feeling hungry (FR) and in increasing food intake in response to negative emotions (EOE).

The CAPS was created with the objective of offering care that prioritizes the rehabilitation and psychosocial reintegration of the mentally ill individual. However, psychiatric hospitalization remains a widely used resource. This study aims to evaluate the rates of psychiatric hospitalizations and the implementation of CAPS in the state of Rio Grande do Sul, from 2008 to 2018. The study has an ecological time series design. As a result, we found a 42% increase in psychiatric hospitalizations. The CAPS coefficient was 0.64 in 2008 and increased to 0.85 (34% higher). The correlation between the CAPS coverage coefficient and the rate of psychiatric hospitalizations in RS exhibited a positive and statistically significant coefficient. These data diverge from what is found in the literature, which indicates a reduction in psychiatric hospitalizations in recent years. Thus, it is possible to conclude that there was an increase in hospitalizations and an increase in CAPS during the study period.

Background Machine learning methods for suicidal behavior so far have failed to be implemented as a prediction tool. In order to use the capabilities of machine learning to model complex phenomenon, we assessed the predictors of suicide risk using state-of-the-art model explanation methods. Methods Prospective cohort study including a community sample of 1,560 young adults aged between 18 and 24. The first wave took place between 2007 and 2009, and the second wave took place between 2012 and 2014. Sociodemographic and clinical characteristics were assessed at baseline. Incidence of suicide risk at five-years of follow-up was the main outcome. The outcome was assessed using the Mini Neuropsychiatric Interview (MINI) at both waves. Results The risk factors for the incidence of suicide risk at follow-up were: female sex, lower socioeconomic status, older age, not studying, presence of common mental disorder symptoms, and poor quality of life. The interaction between overall health and socioeconomic status in relation to suicide risk was also captured and shows a shift from protection to risk by socioeconomic status as overall health increases. Limitations Proximal factors associated with the incidence of suicide risk were not assessed. Conclusions Our findings indicate that factors related to poor quality of life, not studying, and common mental disorder symptoms of young adults are already in place prior to suicide risk. Most factors present critical non-linear patterns that were identified. These findings are clinically relevant because they can help clinicians to early detect suicide risk.

This study aimed to evaluate the prevalence of probable sleep bruxism (SB) in children aged 7-8 years and its association with sleep pattern and the time spent using devices with a screen.A cross-sectional study was conducted with children from Pelotas, Brazil (n = 556). Parents/caregivers were interviewed and provided demographic/socioeconomic information, children's daily screen time, nighttime tooth grinding or clenching, sleep duration and answered the Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids (BRIAN-K-sleep domain). Probable SB was determined based on a positive clinical inspection with/without a positive parental/caregiver's reports of tooth clenching or grinding. Hierarchical Poisson regression was performed.The prevalence of probable SB was 15.83% (n = 88). There was no difference in the probable SB prevalence according to the daily screen time (p = 0.744), and low family socioeconomic status was associated with higher SB prevalence (Prevalence Ratio [PR] = 1.95; 95% Confidence Interval [95% CI]: 1.21-3.17; p = 0.006). Higher scores in the sleep domain of the BRIAN-K scale were associated with probable SB [PR = 1.07; 95% CI: 1.01-1.30; p = 0.013].Difficulties in maintaining sleep and low family socioeconomic status were associated with probable SB in schoolchildren, while screen time spent using devices with a screen was not associated.

Introduction Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients. Methods We analyzed urine samples from 30 SCA3 subjects (including one pre-symptomatic subject), 35 subjects with other forms of ataxia, and 37 healthy controls. To quantify polyQ ATXN3 protein levels, we used our previously developed immunoassay. Results PolyQ ATXN3 can be detected in the urine of SCA3 patients, but not in urine samples from healthy controls or other forms of ataxia. There was a significant statistical association between polyQ ATXN3 levels in urine samples and those in plasma. Further, the levels of polyQ ATXN3 urine associated with an earlier age of SCA3 disease onset. Conclusion As clinical trials for SCA3 advance, urine polyQ ATXN3 protein has potential to be a useful, non-invasive and inexpensive biomarker for SCA3.

We conducted a randomized trial of portable HEPA air cleaners in the homes of children age 6-12 years with asthma in the Yakima Valley, Washington. All families received asthma education while intervention families also received two HEPA cleaners (child's bedroom, living room). We collected 14-day integrated samples of endotoxin in settled dust and PM10 and PM10-2.5 in the air of the children's bedrooms at baseline and one-year follow-up, and used linear regression to compare follow-up levels, adjusting for baseline. Seventy-one families (36 HEPA, 35 control) completed the study. Baseline geometric mean (GSD) endotoxin loadings were 1565 (6.3) EU/m2 and 2110 (4.9) EU/m2 , respectively, in HEPA vs. control homes while PM10 and PM10-2.5 were 22.5 (1.9) μg/m3 and 9.5 (2.9) μg/m3 , respectively, in HEPA homes, and 19.8 (1.8) μg/m3 and 7.7 (2.0) μg/m3 , respectively, in control homes. At follow-up, HEPA families had 46% lower (95% CI, 31%-57%) PM10 on average than control families, consistent with prior studies. In the best-fit heterogeneous slopes model, HEPA families had 49% (95% CI, 6%-110%) and 89% lower (95% CI, 28%-177%) PM10-2.5 at follow-up, respectively, at 50th and 75th percentile baseline concentrations. Endotoxin loadings did not differ significantly at follow-up (4% lower, HEPA homes; 95% CI, -87% to 50%).

This study aimed to assess the association between tobacco smoking and body composition in patients with HIV/AIDS in combination antiretroviral therapy (cART). This is a cross-sectional study with people of HIV followed in specialized care service for HIV patients located in the South of Brazil. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used to assess smoking and other psychoactive substance use. Body mass index (BMI) was calculated as the ratio of body weight (in kilograms) to squared height (in meters). Patients also had their body composition evaluated with a multi-frequency bioelectrical impedance (Bodystat® Quadscan 4000, RU) to estimate skeletal muscle index (SMI). In total, 320 subjects were included in the study. The prevalence of smoking was 54.7%. Tobacco smoking was associated with malnutrition, lower body mass index scores, and lower skeletal muscle mass index. It is concluded that there is a high prevalence of smoking among patients with HIV/AIDS and that this behavior is associated with worse body composition. Thus, it is suggested to implement strategies to support smoking cessation among people with HIV/AIDS. Resumo O objetivo deste estudo foi avaliar a relação entre tabagismo e composição corporal em pacientes com HIV/AIDS em terapia antirretroviral combinada (TARVc). Trata-se de um estudo transversal com portadores de HIV acompanhados em um serviço de atendimento especializado localizado no Sul do Brasil. O instrumento Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) foi utilizado para avaliar o uso de tabaco e outras substâncias psicoativas. O índice de massa corporal (IMC) foi calculado como a razão do peso corporal (em quilogramas) pela altura ao quadrado (em metros). Os pacientes também tiveram sua composição corporal avaliada com uma impedância bioelétrica de múltiplas frequências (Bodystat® Quadscan 4000, RU) a fim de estimar o índice de massa muscular esquelética. No total, 320 sujeitos foram incluídos no estudo. A prevalência de tabagismo foi de 54,7%. O tabagismo foi associado à desnutrição, menores escores do índice de massa corporal e menor índice de massa muscular esquelética. Conclui-se que há uma alta prevalência de tabagismo entre pacientes com HIV/AIDS e que esse comportamento está associado a pior composição corporal. Assim, sugere-se a implementação de estratégias de apoio à cessação do tabagismo entre pessoas com HIV/AIDS.

The present study aims to assess the association between sleep quality and the functional and cognitive impairment in subjects that recently converted to bipolar disorder (BD), subjects with past major depressive disorder (MDD) and subjects with recurrent MDD. This was a cross-sectional study corresponding to a second wave of a cohort study with a community sample. The first wave included 585 subjects diagnosed with MDD. Mood episodes were assessed through structured clinical interview. Functional and objective cognitive impairments were measured by the Functional Assessment Short Test (FAST) and Letter-number sequencing from Wechsler Adult Intelligence Scale III, respectively, and Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) was used for subjective cognition measure. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI). In PSQI, FAST and COBRA, we found significantly worse scores in the BD and recurrent MDD groups when compared to past MDD group. Our findings also showed a significant association between functioning and subjective cognition with general sleep quality in all observed groups. We reinforce the need to follow-up for maintenance of functional and cognitive impairment, notably with BD patients, who may suffer in addition to damage caused by sleep alterations, also with neuroprogression in the long term.

We conducted a randomized trial of portable HEPA air cleaners with pre-filters designed to also reduce NH3 in non-smoking homes of children age 6-12 with asthma in Yakima Valley (Washington, USA). Participants were recruited through the Yakima Valley Farm Workers Clinic asthma education program. All participants received education on home triggers while intervention families additionally received two HEPA cleaners (child's sleeping area, main living area). Fourteen-day integrated samples of PM2.5 and NH3 were measured at baseline and one-year follow-up. We fit ANCOVA models to compare follow-up concentrations in HEPA versus control homes, adjusting for baseline concentrations. Seventy-one households (36 HEPA, 35 control) completed the study. Most were single-family homes, with electric heat and stove, A/C, dogs/cats, and mean (SD) 5.3 (1.8) occupants. In the sleeping area, baseline geometric mean (GSD) PM2.5 was 10.7 (2.3) µg/m3 (HEPA) versus 11.2 (1.9) µg/m3 (control); in the living area, it was 12.5 (2.3) µg/m3 (HEPA) vs. 13.6 (1.9) µg/m3 (control). Baseline sleeping area NH3 was 62.4 (1.6) µg/m3 (HEPA) vs. 65.2 (1.8) µg/m3 (control). At follow-up, HEPA families had 60% (95% CI, 41%-72%; p < 0.0001) and 42% (19%-58%; p = 0.002) lower sleeping and living area PM2.5 , respectively, consistent with prior studies. NH3 reductions were not observed.

In this report, we aim to assess the interaction of bipolar disorder and major depressive disorder with the evolution of social roles, economic classification, and substance misuse in emerging adults. This is a longitudinal population-based study (n = 231 at baseline), in which participants were reassessed at a mean of 5 years after baseline. A structured clinical interview was used to diagnose the participants with bipolar disorder and major depression; a control group without mood disorders was included. Men with mood disorders were less likely to be married in the beginning of the study and less likely to work in the follow-up. Women with major depression were less likely to study and more likely to be in a lower economic class at the beginning of the study. In comparison, women with bipolar disorder were less likely to live with their parents and more likely to live with their children in the first wave of the study. Substance misuse was more likely in people with mood disorders, especially in men, and women with bipolar disorder had the highest likelihood in the follow-up. Albeit longitudinal analyses were limited by a possibly insufficient sample size and mediating mechanisms for change, such as stigma, were not explored, the study suggests sex-related specificities regarding the change in social roles and substance use in people with mood disorders. Emerging adults, especially those with mood disorders, are in a period of change and instability and at a greater risk for substance use and abuse.

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.

Background Studies on the field of mood disorders has mainly focusing on the risk factors associated to develop the illness or the clinical factors associated with the clinical progression. Less attention was given to factors such as resilience that may be associated with better outcomes in the course of mood disorders. In this study, we assessed the mediation effect of resilience on the relationship between childhood trauma and mood disorders, as well as the severity of depressive symptoms in a population-based sample. Methods This is a cross-sectional study with a community sample of young adults with bipolar disorder (BD), major depressive disorder (MDD), and community controls without any mood disorder. The trauma experiences during childhood were assessed by Childhood Trauma Questionnaire (CTQ). The severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and to assess the resilience was used the Resilience Scale (RS-25). Results All subtypes of trauma were associated with both MDD and BD, however, only physical and emotional abuse differentiated BD from MDD subjects. Bootstrapping-enhanced mediation analyses indicated that resilience partly mediated the association of childhood trauma to both mood disorder and severity of depression. Limitation The employed mediation analyses are cross-sectional in nature, which limits any firm conclusions regarding causality. Conclusions The findings support the clinical assumption that resilient subjects may be partly protected against the detrimental long-term effects of childhood trauma. This study provides important information regarding the relationships among childhood trauma, resilience, and mood disorder.

Introduction Childhood trauma has been suggested to be involved in susceptibility to bipolar disorder (BP). However, it remains unclear whether the occurrence of childhood trauma is differently distributed in subthreshold bipolar disorder (SBP). Objective To assess childhood trauma in young adults with SBP, as compared to young adults with BP and population controls (PC). Method This was a cross-sectional, population-based study. The Mini International Neuropsychiatric Interview (MINI) was used to define the groups with BP (subjects with a lifetime or current manic episode or lifetime or current hypomania with a history of a depressive episode), SBP (subjects with a history of hypomanic episode without lifetime or current depressive episode), and subjects without mood disorders (PC). Childhood trauma was assessed using de Childhood Trauma Questionnaire (CTQ). We investigated differences regarding childhood trauma across the three groups (BP, SBP and PC). Result Except for sexual abuse, all subtypes of childhood trauma remained associated with the BP group as compared to PC. Additionally, when we compared SBP and BP, significant differences were found only for emotional abuse. No significant differences were found in relation to childhood trauma between the SBP and PC groups after adjusting for confounding factors. Conclusion These findings suggest that investigating childhood trauma, with a particular focus on emotional abuse, could be considered a preventive measure and potentially improve the prognosis.

Background While little is known about the occupational hazards associated with Cannabis cultivation, both historical research in the hemp industry and preliminary data from modern grow houses, suggest that Cannabis workers may be at increased risk of respiratory and allergic diseases. Objectives We sought to investigate the association between workplace exposures and health symptoms in an indoor Cannabis grow facility in Washington State, USA. Methods We performed a cross-sectional study with all consenting employees in an indoor Cannabis grow facility in Seattle, WA using a questionnaire. The questionnaire gathered data on respiratory, ocular, nasal, and dermal symptoms. A subset of employees with work-related symptoms underwent repeated cross-shift and cross-week measurement of spirometry, fractional exhaled nitrogen oxide (FeNO), and skin prick testing for Cannabis sensitization. Exposure to Cannabis dust was classified based on self-described tasks, expert opinion, and exposure monitoring of particulate matter. Multivariable logistic regression was undertaken to examine associations between exposure to Cannabis dust (classified as low, medium, and high) and health symptoms. Linear mixed effects models examined the relationship between cross-shift and cross-week changes in spirometry and FeNO. Results Ninety-seven percent (97%) of the employees (n = 31) surveyed were recreational cannabis users, with 81% (n = 25) smoking cannabis multiple times per day. Twenty-two (71%) employees reported one or more work-related symptoms: 65% respiratory, 39% ocular, 32% nasal, and 26% dermal symptoms. There was a trend toward increased likelihood of work-related symptoms with increasing exposure to Cannabis dust, although none of these results were statistically significant. Of the 10 employees with work-aggravated symptoms, 5 had borderline-high or high FeNO, 7 had abnormal spirometry, and 5 had evidence of Cannabis sensitization on skin prick testing. FeNO increased by 3.78 ppb (95% confidence interval 0.68–6.88 ppb) across the work-week and there was a trend toward cross-week and cross-shift reduced airflow. Conclusions We found a high prevalence of work-related allergic- and particularly respiratory symptoms in the employees of one indoor Cannabis grow facility in Washington State. A high proportion of employees with work-aggravated symptoms had findings consistent with probable work-related asthma based on high FeNO, airflow obstruction on spirometry, and Cannabis sensitization on skin prick testing. However, due to the high incidence of recreational cannabis use among these workers, the relative influence of occupational versus recreational exposure to Cannabis dust on the respiratory health and sensitization status of these workers could not be resolved in this study.

Background A number of theories associate emotional factors with the triggering of sleep bruxism (SB). Few studies have used validated instruments to assess psychological characteristics and SB in children. In this study, the authors aimed to assess the prevalence of parent-reported SB in children and its association with social, emotional, and behavioral problems. Methods The authors conducted a cross-sectional study with a school-based sample at 20 public schools in Brazil. Parents or caregivers provided information related to tooth-grinding sounds during sleep and about children’s social, emotional, and behavioral problems by using the Strength and Difficulties Questionnaire. Analyses were carried out considering each subscale of the Strength and Difficulties Questionnaire and the total score. The authors estimated prevalence ratios by using a Poisson regression model. Statistical inferences were based on 95% confidence intervals. Results A total of 556 children aged 8 years were included. Prevalence of SB was 30.83%. Results of an adjusted analysis showed a significant association of SB with higher scores on total difficulties (overall score) (P Conclusions Parental reports of emotional and behavioral problems were associated with a higher prevalence of SB in schoolchildren. Practical Implications This study’s results contribute to those of previous investigations about the association between psychological characteristics and SB. Interdisciplinary research involving dentistry and psychology may improve the understanding of bruxism.

Suicide is the second leading cause of death among young adults worldwide, and few studies have assessed the factors associated with suicidality in this specific population. Thus, the aim of this study was to assess the association between mixed episodes and suicidality in a community sample of young adults. For this aim, we compared young adults in a mixed episode with individuals in a depressive or (hypo)manic episode, and community controls.This is a cross-sectional population-based study including young adults aged 18-24 years old. Information about participants' age, sex, self-reported skin color and study status were obtained using a sociodemographic questionnaire. Mixed, (hypo)manic and depressive episodes, as well as suicide risk were assessed using the Mini International Neuropsychiatric Interview.The sample included 1560 individuals. Young adults in a mixed episode showed a 13.50 times higher probability to have suicide risk, as compared to community controls (p 0.001), 5.67 higher probability to have suicide risk as compared to individuals in a (hypo)manic episode (p 0.001), and 2.18 times higher probability to have suicide risk as compared to young adults in a depressive episode (p 0.001).The assessment of suicide risk includes both suicide attempts and ideation.Young adults in a mixed episode showed a higher rate of suicide risk than individuals with depression or mania/hypomania. Considering the already increasing prevalence of suicide among young adults, there is an urgent need for the early diagnosis and treatment of mixed episodes in this specific population.

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f −/− mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.

Prior studies have found an especially high prevalence of illicit substance use among adolescents and young adults in Brazil. The current study aimed to employ machine learning techniques to identify predictors of illicit substance abuse/dependence among a large community sample of young adults followed for 5 years. This prospective, population-based cohort study included a sample of young adults between the ages of 18-24 years from Pelotas, Brazil at baseline (T1). The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used to assess illicit substance abuse/dependence. A clinical interview was conducted to collect data on sociodemographic characteristics and psychopathology. Elastic net was used to generate a regularized linear model for the machine learning component of this study, which followed standard machine learning protocols. A total of 1560 young adults were assessed at T1, while 1244 were reassessed at the 5-year follow-up period (T2). The strongest predictors of illicit substance abuse/dependence at baseline (AUC of 0.83) were alcohol abuse/dependence, tobacco abuse/dependence, being in a current major depressive episode, history of a lifetime manic episode, current suicide risk, and male sex. The strongest predictors for illicit substance abuse/dependence at the 5-year follow-up (AUC: 0.79) were tobacco abuse/dependence at T1, history of a lifetime manic episode at T1, male sex, alcohol abuse/dependence at T1, and current suicide risk at T1. Our findings indicate that machine learning techniques hold the potential to predict illicit substance abuse/dependence among young adults using sociodemographic/clinical characteristics, with relatively high accuracy.

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord1. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing2-4. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies5,6, but how those variants increase risk for disease is unknown. Here we show that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harbouring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function.

Depression is a disabling illness with complex etiology. While the catechol-O-methyltransferase (COMT) gene, in particular the functional Val

The aberrant translation of a repeat expansion in chromosome 9 open reading frame 72 (C9orf72), the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), results in the accumulation of toxic dipeptide repeat (DPR) proteins in the central nervous system We have found that, among the sense DPR proteins, HDAC6 specifically interacts with the poly (GA) and co-localizes with inclusions in both patient tissue and a mouse model of this disease (c9FTD/ALS). Overexpression of HDAC6 increased poly (GA) levels in cultured cells independently of HDAC6 deacetylase activity, suggesting that HDAC6 can modulate poly (GA) pathology through a mechanism that depends upon their physical interaction. Moreover, decreasing HDAC6 expression by stereotaxic injection of antisense oligonucleotides significantly reduced the number of poly (GA) inclusions in c9FTD/ALS mice. These findings suggest that pharmacologically reducing HDAC6 levels could be of therapeutic value in c9FTD/ALS.

Background Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children. Methods Seventy-five children with poorly controlled asthma and living in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. The Asthma Control Test (ACT) score, asthma symptoms in prior 2 weeks, unplanned clinical utilization, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and additional secondary outcomes were evaluated at baseline, six, and 12 months. Group differences were assessed using multivariable-adjusted generalized estimating equations. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models in secondary analysis. Results Mean child age was 9.2 and 8.6 years in intervention and control groups, respectively, and two-thirds of participants were male. Primary analysis of repeated measures of ACT score did not differ between groups (HEPA group mean change compared to controls 10% [95% CI: − 12-39%]). A suggestion of greater decrease in uLTE4 (ng/mg creatinine) was observed (− 10% [95% CI: − 20 -1%]). Secondary analysis showed children with HEPAs were less likely to have an ACT score meeting a clinically defined cutoff for poorly controlled asthma using repeated measures (IRR: 0.45 [95% CI: 0.21–0.97]). In Poisson models, intervention participants had reduced risk of ever meeting this cutoff (IRR: 0.43 [95% CI: 0.21–0.89]), ever having symptoms in the past 2 weeks (IRR: 0.71 [95% CI: 0.52–0.98]), and lower risk of any unplanned clinical utilization (IRR: 0.35 [95% CI: 0.13–0.94]) compared to control participants. Discussion The HAPI study showed generally improved outcomes among children in the HEPA air cleaner group. However, primary analyses did not meet statistical significance and many outcomes were subjective (self-report) in this unblinded study, so findings must be interpreted cautiously. HEPA air cleaners may provide additional benefit for child asthma health where traditional asthmagens (traffic, tobacco smoke) are not prominent factors, but larger studies with more statistical power and blinded designs are needed. Trial registration ClinicalTrials.gov Identifier: NCT04919915. Date of retrospective registration: May 19, 2021.

A major function of TAR DNA-binding protein-43 (TDP-43) is to repress the inclusion of cryptic exons during RNA splicing. One of these cryptic exons is in UNC13A, a genetic risk factor for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of cryptic UNC13A in disease is heightened by the presence of a risk haplotype located within the cryptic exon itself. Here, we revealed that TDP-43 extreme N-terminus is important to repress UNC13A cryptic exon inclusion. Further, we found hnRNP L, hnRNP A1, and hnRNP A2B1 bind UNC13A RNA and repress cryptic exon inclusion, independently of TDP-43. Finally, higher levels of hnRNP L protein associate with lower burden of UNC13A cryptic RNA in ALS/FTD brains. Our findings suggest that while TDP-43 is the main repressor of UNC13A cryptic exon inclusion, other hnRNPs contribute to its regulation and may potentially function as disease modifiers.

Background Bipolar disorder (BD) has a high heritability rate. Current studies have been dedicated to identifying prodromes of BD in the offspring of parents with BD (BO), and the sleep patterns of these individuals have been considered important factors. Objective To describe the changes in sleep parameters among offspring of parents with BD when compared to offspring of controls and to identify if changes in parameters and quality of sleep predict the onset of BD among these individuals. Methods PubMed, PsycINFO, and Embasewere systematically searched with no year or language restrictions, up to August 18, 2020. We searched for a combination of the following search items ("sleep*") AND ("bipolar disorder*" OR "mania" OR "hypomania" OR "bipolar depression") AND ("ultra-high risk" OR "high risk" OR "offspring" OR "first degree relatives"). Results A total of 10 studies were included in the systematic review and 4 studies were included in the meta-analysis. Our meta-analysis showed that the BO showed greater daytime sleepiness as compared to the offspring of control parents. The systematic review indicates that shorter sleep duration, sleep disorders and other related features can differentiate the two groups. Finally, some sleep patterns such as: decreased sleep, difficulty falling asleep, and overall sleep problems might be predictors for the development of BD. Conclusion To describe the changes in sleep parameters among offspring of parents with BD when compared to offspring of controls and to identify if changes in parameters and quality of sleep predict the onset of BD among these individuals.

The aim of this paper is to analyse the factors associated with the dropout from brief psychotherapy for adults with major depressive disorder (MDD) treated at a mental health outpatient clinic. This is a randomized clinical trial with two models of psychotherapy: cognitive behavioural therapy (CBT) and supportive expressive dynamic psychotherapy (SEDP). MDD and anxiety disorders were evaluated through the Mini International Neuropsychiatric Interview-Plus. The personality disorders were evaluated by the Millon Clinical Multiaxial Inventory-III. The severity of depressive symptoms was measured using the Beck Depression Inventory-II and resilience through Resilience Scale. Of the 215 participants, 41.9% abandoned psychotherapy (n = 90), and, of these, 54.4% (n = 49) abandoned after the fourth session. The proportion of psychotherapy dropout was higher among those with nonwhite skin colour, belonging to economic classes C and D, who had children and whose depressive symptoms were moderate. Presence of obsessive-compulsive personality trait was protective against dropout. The damage caused by this abrupt interruption is evident for all those involved in the psychotherapeutic process, so the clinician should pay attention to the predictors found in this study in order to develop strategies that promote therapeutic adherence.

The CACNA1C gene encodes the pore-forming alpha-1c subunit of L-type voltage-gated calcium channels. The calcium influx through these channels regulates the transcription of the brain-derived neurotrophic factor (BDNF). Polymorphisms in this gene have been consistently associated with psychiatric disorders, and alterations in BDNF levels are a possible biological mechanism to explain such associations. Here, we sought to investigate the effect of the CACNA1C rs1006737 and rs4765913 polymorphisms and their haplotypes on serum BDNF concentration. We further aim to investigate the regulatory function of these SNPs and the ones linked to them. The study enrolled 641 young adults (362 women and 279 men) in a cross-sectional population-based survey. Linear regression was used to test the effects of polymorphisms and haplotypes on BDNF levels adjusted for potential confounders. Moreover, regulatory putative functional roles were assessed using in silico approach. BDNF levels were not associated with CACNA1C polymorphisms/haplotype in the total sample. When the sample was stratified by sex, checking the effect of polymorphisms on men and women separately, the A-allele of rs4765913 was associated with lower BDNF levels in women compared with the TT genotype (p = 0.010). The AA (rs1006737-rs4765913) haplotype was associated with BDNF levels in opposite directions regarding sex, with lower levels of BDNF in women (p = 0.040) compared to those without this haplotype, while with higher levels in men (p = 0.027). These findings were supported by the presence of regulatory marks only on the male fetal brain. Our results suggest that the BDNF levels regulation may be a potential mechanism underpinning the association between CACNA1C and psychiatric disorders, with a differential role in women and men.

To evaluate the impact of defense mechanisms at baseline on depressive symptoms after brief psychotherapies and after 6-months of follow-up among depressed patients with and without cluster B personality disorders (PDs).This quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18-60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. The Millon Clinical Multiaxial Inventory-III was applied to assess PD, the Defense Style Questionnaire 40 was used to analyze defense mechanisms, and the Beck Depression Inventory was used to measure the severity of depressive symptoms. Adjusted analysis was performed by linear regression.The final sample consisted of 177 patients diagnosed with major depressive disorder, of whom 39.5% had cluster B PDs. Immature defenses at baseline significantly predicted the persistence of depressive symptoms at post-intervention and at 6-months of follow-up only in patients with PDs.In depressed patients with cluster B PDs, immature defenses predicted a poor response to brief therapies. The assessment of immature defenses at baseline can help identify patients at greater risk of poor therapeutic results and enable more appropriate treatment choices.

Hospitalized patients with COVID-19 show increased serum concentrations of neurofilament light chain that correlate with worse clinical outcomes., Brain damage marker in COVID-19 SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), causes neurological manifestations in a substantial proportion of patients. Determining the extent of neuronal injury is essential to better understand disease pathophysiology and to evaluate potential therapies. Prudencio et al. analyzed serum from 142 patients hospitalized with COVID-19 and showed that the expression of the neurofilament light protein (NFL), a marker of neuroaxonal injury, was elevated compared to healthy controls. In addition, serum NFL expression correlated with disease severity and tended to be reduced in subjects treated with remdesivir. The results suggest that serum NFL analysis should be incorporated when evaluating therapeutic trials for COVID-19., Brain imaging studies of patients with COVID-19 show evidence of macro- and microhemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias, and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In 100 hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

Introduction The Brazilian psychiatric reform has revolutionized the way that mental health care is provided all over the country, introducing the Psychosocial Care Centers (CAPS) and encouraging care at liberty. The CAPS have been assigned many objectives, such as prevention of hospitalizations and intervention in crises or suicide. This paper aims to describe the correlation between the implementation of CAPS and the rates of psychiatric hospitalizations and suicides from 2008 to 2018. Methods This study has an ecological time series design and included residents of the city of Porto Alegre, RS, Brazil, who were hospitalized through the Sistema Único de Saúde (SUS). The data were obtained from official databases (DATASUS, CNES, and IBGE) and indicators were calculated (CAPS coverage, hospitalization rate, and suicide rate). Associations between the indicators were tested using Pearson’s correlation coefficients. Results We found a negative correlation between provision of CAPS and psychiatric hospitalizations (r = -0.607 p = 0.048). Conclusion These results support the hypothesis that there is a negative correlation between implementation of the CAPS and psychiatric hospitalizations. This reinforces the importance of implementing policies related to improving psychiatric reform.

Leptin is an anorexigenic hormone well recognized by its role in mediating energy homeostasis. Recently, leptin has been associated with psychiatric disorders and interestingly, leptin treatment has shown antidepressant and anxiolytic effects. We examined the association of leptin levels and leptin (LEP) gene rs3828942 polymorphism with anxiety disorders considering sex differences. A cross-sectional population-based study, including 1067 young adults, of whom 291 presented anxiety disorders diagnosed by the Mini International Neuropsychiatric Interview (MINI 5.0). The rs3828942 polymorphism was genotyped by real-time PCR and ELISA measured leptin levels. Leptin levels were not associated with anxiety disorders after adjusting for sex and body mass index (BMI) [ß = - 0.009 (- 0.090-0.072); p = 0.832]. The distribution of rs3828942 genotypes was not associated with anxiety disorders. However, in a sex-stratified sample, the A-allele of rs3828942 polymorphism was associated with risk for GAD in women even when adjusting for confounding variables [OR = 1.87 (1.17-2.98); p = 0.008]. In a subsample of 202 individuals with GAD and control matched by sex and BMI, results suggest an interaction between genotypes and GAD diagnosis based on leptin levels only in the male group [F (1, 54) = 6.464; p = 0.0139]. Leptin is suggested to be related with the neurobiology of anxiety disorders in a sex-dependent manner since women carrying the A-allele of LEP rs3828942 present a higher risk for GAD, while leptin levels seem to be lower in men with GAD carrying A-allele. Studies on the relationship between leptin polymorphisms and levels are scarce and, therefore, further research is necessary.

This study aims to assess the effect of childhood trauma on the outcomes of brief cognitive therapies for major depressive disorder. This is a follow-up clinical study nested in a randomized clinical trial of cognitive therapies. Sixty-one patients were assessed at baseline, post-intervention and six-month follow-up. The study showed that brief cognitive therapies improved depressive and anxious symptoms at post-intervention and six-month follow-up. Higher childhood trauma scores at baseline were significantly associated with higher severity of depressive and anxious symptoms at six-month follow-up. Longer courses of psychotherapy may be needed to improve the long-lasting effects of traumatic experiences.

Biological rhythm is the daily metabolic cycle of mammals that involves the sleep-wake cycles, hormone release, eating habits and digestion, body temperature, and other important bodily functions that are repeated daily. Thus, greater difficulty in maintaining the circadian rhythms may be involved in the increased risk of obesity. This study assessed the association between biological rhythm disruption and childhood obesity among school children.This is a cross-sectional study with 7-8-year-old school children enrolled in a public school in the city of Pelotas-RS. The sample was drawn through multistage sampling. The Biological Rhythms Interview of Assessment in Neuropsychiatry-Kids (BRIAN-Kids) was used to assess the degree of difficulty maintaining the biological rhythm. BMI was calculated as weight/heightA total of 596 children and their caregivers participated in this study. The prevalence of obesity was 24% among school children, 28.9% for girls, and 19.4 for boys (p = 0.009). Obese children had greater difficulties in maintaining the biological rhythm compared to nonobese children (p = 0.007). Some of these difficulties included sleep (p = 0.008), overall activities (p = 0.027), social rhythm (p = 0.033), and eating (p = 0.032) pattern.Approximately one-quarter of children were obese. This finding was associated with the caregiver characteristics and some difficulties in maintaining the biological rhythm.

Objective: The purpose of this study was to assess the efficacy and tolerability of tianeptine as an adjunctive maintenance treatment for bipolar depression. Methods: This is a multicenter double-blind randomized placebo-controlled maintenance trial of adjunctive tianeptine 37.5 mg/day. Participants ( n=161) had a Montgomery-Asberg Depression Rating Scale ⩾12 at entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine ( n=69) were randomized to adjunctive tianeptine ( n=36) or placebo ( n=33) in addition to usual treatment. Kaplan-Meier estimates and the Mantel-Cox log-rank test were used to evaluate differences in time to intervention for a mood episode between the tianeptine and placebo groups. We also assessed overall functioning, biological rhythms, quality of life, rates of manic switch and serum brain-derived neurotrophic factor levels. Results: There were no differences between adjunctive tianeptine or placebo regarding time to intervention or depression scores in the 24-week double-blind controlled phase. Patients in the tianeptine group showed better performance in the letter-number sequencing subtest from the Wechsler Adult Intelligence Scale at the endpoint ( p=0.014). Tianeptine was well tolerated and not associated with higher risk for manic switch compared to placebo. Conclusion: Tianeptine was not more effective than placebo in the maintenance treatment of bipolar depression. There is preliminary evidence suggesting a pro-cognitive effect of tianeptine in working memory compared to placebo.

Tauopathies are neurodegenerative disorders characterized by aggregation of microtubule associated tau protein in neurons and glia. They are clinically and pathologically heterogeneous depending on the isoform of tau protein that accumulates (three or four 31-to-32-amino-acid repeats [3R or 4R] in the microtubule binding domain), as well as the cellular and neuroanatomical distribution of tau pathology. Growing evidence suggests that distinct tau conformers may contribute to the characteristic features of various tauopathies. Globular glial tauopathy (GGT) is a rare 4R tauopathy with globular cytoplasmic inclusions within neurons and glial cells. Given the unique cellular distribution and morphology of tau pathology in GGT, we sought to determine if tau species in GGT had distinctive biological properties. To address this question, we performed seeding analyses with postmortem brain tissues using a commercial tau biosensor cell line. We found that brain lysates from GGT cases had significantly higher seeding competency than other tauopathies, including corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The robust seeding activity of GGT brain lysates was independent of phosphorylated tau burden and diminished upon removal of tau from samples, suggesting that seeding properties were indeed mediated by tau in the lysates. In addition, cellular inclusions in the tau biosensor cell line induced by GGT had a distinct, globular morphology that was markedly different from inclusions induced by other tauopathies, further highlighting the unique nature of tau species in GGT. Characterization of different tau species in GGT showed that detergent-insoluble, fibril-like tau contained the highest seeding activity, as reflected in its ability to increase tau aggregation in primary glial cultures. Taken together, our data suggest that unique seeding properties differentiate GGT-tau from other tauopathies, which provides new insight into pathogenic heterogeneity of primary neurodegenerative tauopathies. Electronic supplementary material The online version of this article (10.1186/s40478-019-0691-9) contains supplementary material, which is available to authorized users.

Pathogenic mutations in the tau gene (microtubule associated protein tau, MAPT) are linked to the onset of tauopathy, but the A152T variant is unique in acting as a risk factor for a range of disorders including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). In order to provide insight into the mechanism by which A152T modulates disease risk, we developed a novel mouse model utilizing somatic brain transgenesis with adeno-associated virus (AAV) to drive tau expression in vivo, and validated the model by confirming the distinct biochemical features of A152T tau in postmortem brain tissue from human carriers. Specifically, TauA152T-AAV mice exhibited increased tau phosphorylation that unlike animals expressing the pathogenic P301L mutation remained localized to the soluble fraction. To investigate the possibility that the A152T variant might alter the phosphorylation state of tau on T152 or the neighboring T153 residue, we generated a novel antibody that revealed significant accumulation of soluble tau species that were hyperphosphorylated on T153 (pT153) in TauA152T-AAV mice, which were absent the soluble fraction of TauP301L-AAV mice. Providing new insight into the role of A152T in modifying risk of tauopathy, as well as validating the TauA152T-AAV model, we demonstrate that the presence of soluble pT153-positive tau species in human postmortem brain tissue differentiates A152T carriers from noncarriers, independent of disease classification. These results implicate both phosphorylation of T153 and an altered solubility profile in the mechanism by which A152T modulates disease risk. Electronic supplementary material The online version of this article (10.1186/s40478-019-0661-2) contains supplementary material, which is available to authorized users.

Subjects with bipolar disorder suffering of a depressive episode are frequently misdiagnosed as unipolar depression, being important studies assessing the differential diagnosis between bipolar and unipolar depression.To assess the sociodemographic and clinical features of drug-free young adults in a depressive episode of bipolar or unipolar disorder in order to identify factors that may differentiate these psychiatric conditions.This is a cross-sectional study with 241 young adults aged between 18 and 29 years who were evaluated using the Structured Clinical Interview for DSM-IV (SCID). The sample comprised patients with BD (n = 89) and major depressive disorder (n = 152), experiencing a depressive episode and not using psychoactive drugs or illicit psychoactive substances.The characteristics associated with bipolar depression were being male (p 0.001), with a family history of BD (p = 0.013), a higher frequency of childhood traumatic experiences (p = 0.001), younger age of onset of mood disorder (p = 0.004), many previous depressive episodes (p = 0.027), greater severity of depressive symptoms (p 0.001) and day/night reversal (p = 0.013). Those with unipolar depression showed a higher frequency of biological rhythm disturbances (p 0.001), and diurnal preference (p = 0.028).The sample has not included subjects with severe suicide risk, a possible important marker in differentiate unipolar from bipolar depression.Some clinical aspects may contribute to an early differential diagnosis of both bipolar and unipolar depression even in the initial stages of the disease.

The aim of this study was to assess the association between anhedonia and metabolic syndrome (MetS) in a well-characterized community sample of individuals with a current depressive episode. This is a cross-sectional study with young adults aged 24-30 years old. Depressive episode and the presence of anhedonia was assessed using the Mini International Neuropsychiatric Interview - Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). The sample included 931 subjects, being 22 had depression without anhedonia, whereas 55 had depression with anhedonia. MetS was more prevalent among subjects with depression and anhedonia (43.6%) when compared to individuals without anhedonia and population control group. Moreover, subjects with depression and anhedonia have a significant increase of levels of glucose, triglycerides, total-cholesterol and LDL-cholesterol, as well as significant decreased in the HDL-cholesterol level. The present study showed that individuals with depression and anhedonia present higher prevalence of MetS. Our study suggests that the use of the concept of anhedonia may contribute to a better understanding of the complex relationship between depression and metabolic syndrome.