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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.

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.

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.

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.

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.

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.

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

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.

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.

Objective To evaluate the prevalence of Internet addiction (IA) and its associated factors among students at an Educational Institution in Southern Brazil. Method This is a cross-sectional study, targeting a sample of students aged from 14 to 20 years. They were selected by random sampling to be representative of the 4038 students enrolled at the institute at the time. IA was assessed using the Internet Addiction Test (IAT). Screening for anxiety and/or depressive disorders was performed using the Well-Being Index (WHO-5). Results The prevalence of IA was 50.8% and the rate was higher among individuals who had screened positive for depressive or anxiety disorders than among those who had not (p = 0.003). There was an association between IA and access to certain types of content, such as gaming (p = 0.010), work and study related content (p = 0.030), and using the internet to access sexual content (p < 0.001). Conclusion Further studies are needed to confirm the high prevalence of IA and explore factors associated with it in samples with similar characteristics to ours. The associations between this dependency and positive screening for anxiety and/or depressive disorders and the types of content accessed are an alert to the existence of these important relationships and illustrate the importance of studying them further. Knowledge about these associations provides an opportunity to implement measures for prevention, such as psychoeducation, and to offer adequate treatment.

Emotional and behavioral problems have been considered an indicative of mental disorder in children. Mental health problems affect 10-20% of children and adolescents living in low-income and middle-income countries. Evidence suggests that disruptions in the biological rhythm may be a primary cause of emotional and behavioral changes, which affects several psychological functions and moods. Thus, this study aimed at verifying the association between biological rhythm and emotional and behavioral problems in schoolchildren living in Southern Brazil. This is a cross-sectional study with a school-based sample conducted between August 2015 and November 2016. The presence of emotional and behavioral problems in children was verified by the Strengths and Difficulties Questionnaire (SDQ), parents' version. This is a 25-item assessment questionnaire used to screen mental health problems in children and adolescents (from 4 to 17 years of age) in the last 6 months. The Biological Rhythm Interview of Assessment in Neuropsychiatry-Kids (BRIAN-K) was used to measure the degree of biological rhythm disruption. The BRIAN-K consists of 20 items; from among these, 17 items are added to generate a quantitative measure, with greater scores indicating more biological rhythm disruption. The final score can also be divided into four subscales: sleep, social rhythm, eating pattern and overall activities. A total of 609 children responded to the assessment instruments. With regard to parents or primary caregiver, 596 completed the assessment and 13 (2%) were not located or refused to participate in the study. Thus, 596 dyads were included in the analysis. Children with emotional and behavioral problems presented higher scores in all domains of BRIAN-K: sleep, social, activity, eating pattern and total score (p 0.001). The following variables remained associated with emotional and behavioral problems after adjusted analysis: BRIAN-K total score (p 0.001) and all subscales sleep (p 0.001), social (p 0.001), activity (p 0.001) and eating pattern (p 0.001). Children with emotional and behavioral problems presented higher biological rhythm disruption when compared with children without emotional and behavioral problems. Our study emphasizes the importance of biological rhythm and its influence on emotional and behavioral problems in schoolchildren. Early detection of any biological rhythm disruption may enhance further assessment of any eventual emotional and behavioral problem and even a psychopathology.

Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and schizophrenia. Here, we examined an association between a single nucleotide polymorphism in A(2A) receptor gene (ADORA2A, rs2298383 SNP) with current depressive episode and symptom profile. A total of 1253 individuals from a cross-sectional population-based study were analyzed by the Mini International Neuropsychiatric Interview 5.0. Our data showed that the TT genotype of ADORA2A rs2298383 SNP was associated with reduced risk for depression when compared to the CC/CT genotypes (p = 0.020). This association remained significant after adjusting for confounding variables such as smoking, gender, socioeconomic class, and ethnicity (OR = 0.631 (95% CI 0.425–0.937); p = 0.022). Regarding the symptoms associated with depression, we evaluated the impact of the ADORA2A SNP in the occurrence of sad/discouraged mood, anhedonia, appetite changes, sleep disturbances, motion changes, energy loss, feelings of worthless or guilty, difficulty in concentrating, and presence of bad thoughts. Notably, the TT genotype was independently associated with reduced sleep disturbances (OR = 0.438 (95% CI 0.258–0.743); p = 0.002) and less difficulty in concentrating (OR = 0.534 (95% CI 0.316–0.901; p = 0.019). The cross-sectional design cannot evaluate the cause-effect relationship and did not evaluate the functional consequences of this polymorphism. Our data support an important role for ADORA2A rs2298383 SNP in clinical heterogeneity associated with depression. The presence of the TT genotype was associated with decrease risk for current depression and disturbances in sleep and attention, two of the most common symptoms associated with this disorder.

Objective The aim of this study was to verify the serum GDNF levels in individuals with anxiety disorder (AD) in a population-based study. Methods This was a cross-sectional study population-based, with people aged 18 to 35. AD's assessment was performed using the Mini International Neuropsychiatric Interview (M.I.N.I). Serum GDNF was measured by ELISA using a commercial kit. Results The prevalence was 3.3% for post-traumatic stress disorder, 6.7% for panic disorders, 17% generalized anxiety disorder, 5.1% for obsessive- compulsive disorder and 7.5% for social phobia. Serum GDNF levels was higher in individuals with panic disorders (p = 0.013), generalized anxiety (p = 0.035), obsessive- compulsive disorder (p = 0.005) and social phobia (p = 0.004), when compared to individuals without ADs. Only post traumatic stress disorder is not associated with serum GDNF levels (p = 0.119). Conclusion In this paper, we observed increased serum levels of GDNF in individuals with anxiety disorders, suggesting that this biomarker can be used as a putative marker for AD's. The knowledge of the physiological changes related to anxiety disorders can provide a better understanding of AD's pathogenesis, as well as, mechanisms involved in the progression of this condition.

Introduction Biological rhythm is associated with the level of alertness, cognitive performance and mood of the individuals. Its regularity is essential to preserve good health and quality of life. Objective To present the steps for the construction of the scale entitled Biological Rhythm Interview of Assessment in Neuropsychiatry – Kids (BRIAN-K), designed to measure biological rhythm disruptions in Brazilian children and adolescents. Methods Items were developed following the adult version of the scale. Analysis of the psychometric characteristics of the scale was based on the responses of 373 parents/caregivers of school age children (7 and 8 years old). Results A theoretical model of 17 items with the purpose of evaluating four domains (sleep, activities, social rhythm and eating pattern) was determined using exploratory factor analysis (EFA) and via identification of a general factor. The psychometric properties of the BRIAN-K showed favorable properties. Conclusion Only two items needed to be rewritten. Further studies are needed to investigate the instrument's adequacy to different age groups and additional evidence of validity and reliability.

Objective: To evaluate the association between abuse of and dependence on different psychoactive substances and the presence of anxiety disorders in a sample of young adults from a city in southern Brazil. Methods: Between 2007 and 2009, we carried out a cross-sectional, population-based study of individuals aged 18-24 years who lived in Pelotas, a city in southern Brazil. We evaluated anxiety disorders using the Mini International Neuropsychiatric Interview 5.0 (MINI), and use of psychoactive substances with the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST 2.0/0MS). We used Fisher’s exact test for univariate analysis, and Poisson regression models with robust variance for multivariable analysis. Results: The sample consisted of 1,560 young adults. The overall prevalence of abuse/dependence was 26.9% for alcohol, 24.9% for tobacco, and 7.3% for illicit substances. Individuals with agoraphobia had a 32% higher prevalence of tobacco abuse/dependence (prevalence ratio [PR] = 1.32 [95%CI 1.01-1.74]). Individuals with posttraumatic stress disorder (PTSD) or generalized anxiety disorder (GAD) had a 2.41-fold (95%CI 1.22-4.77) and 1.76-fold (95%CI 1.00-3.11) higher prevalence of illicit substance abuse/dependence, respectively. Conclusion: In this population-based sample, we found associations between GAD, PTSD, and increased prevalence of illicit substance abuse/dependence. In addition, individuals with agoraphobia seem to have increased tobacco abuse/dependence.

Objective To assess the prospective associations of mood disorders and suicidality in a community sample of young adults from south Brazil. Method Prospective population-based cohort study. Young adults (18-24 years old) were recruited and followed up on 5 years later; people were interviewed at their homes. Suicidality, as well as mood and anxiety disorders, was assessed using the Mini-International Neuropsychiatric Interview. The impact of mood episodes on suicidality was both evaluated when they occurred in the same wave (a current episode) and when suicidality occurred prospectively, with suicidality measured at follow-up (a past episode). Results The sample included 1560 young adults at baseline, with 1244 reassessed at follow-up (80.6%). Depressive episodes, both current and past, had a significant impact on suicidality in the final multivariable model. Manic episodes, however, were less consistently associated with suicidality. Conclusion Depressive episodes have a strong, independent, and robust association with prospective suicidality. The association between manic episodes and suicidality, on the other hand, was dependent on the analysis and deserves further exploration.

This study aimed to compare the effectiveness of narrative cognitive therapy (NCT) and cognitive behavior therapy (CBT) in the improvement of perception of quality of life in young adults with depression at 12-month follow-up. This was a randomized clinical trial conducted using seven sessions of NCT or CBT. Quality of life was measured using the Medical Outcomes Survey Short-Form General Health Survey. The sample included 97 patients. Considering only completers to be samples, CBT was more effective than NCT for improvement of physical functioning (p = 0.031), vitality (p = 0.013), and mental health (p = 0.002) at 12-month follow-up. However, in the intention-to-treat analysis, we found no difference between groups. Regardless of model, we found a significant improvement in all domains from baseline to postintervention and 6- and 12-month follow-ups, except for the bodily pain domain. In conclusion, both models were effective in the improvement of perception of quality of life.

Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD.

OBJECTIVE To assess the global functioning and clinical outcomes of children and adolescents with bipolar disorder, children and adolescents with bipolar disorder and substance use disorder (SUD) comorbidity and healthy controls. METHODS This study had a cross-sectional design. Participants were children and adolescents aged between 6 and 17 years, and data were collected between 2003 and 2015. Psychiatric diagnosis was established according to DSM-IV criteria using the Kiddie-SADS-Present and Lifetime Version or the Mini-International Neuropsychiatric Interview for Children and Adolescents. Global functioning was assessed using the Children's Global Assessment Scale. Depressive symptoms were assessed using the Children's Depression Rating Scale. Manic symptoms were measured using the Young Mania Rating Scale, and the severity of anxious symptoms was assessed using the Screen for Child Anxiety Related Disorders. RESULTS The sample included 187 children and adolescents with bipolar disorder, 29 with BD and SUD comorbidity, and 115 healthy controls. Children and adolescents with BD and SUD comorbidity presented later onset of mood disorder (P < .001); higher rates of lifetime history of suicide attempt (P < .001), lifetime history of psychosis (trend toward significance: P = .076), and lifetime hospitalization (P < .001); and higher severity of depressive symptoms (trend toward significance: P = .080) as compared to those with BD without SUD comorbidity. In addition, both diagnosis groups presented higher rates of functional impairment when compared to controls (P < .001). Moreover, BD and SUD comorbidity presented higher functional impairment, as compared to BD without SUD comorbidity (P = .020). CONCLUSIONS Children and adolescents with bipolar disorder and substance use disorder comorbidity present a worse clinical course than those with bipolar disorder but without substance use disorder comorbidity.

Studies on gene x environment interaction (GxE) have provided vital information for uncovering the origins of complex diseases. When considering the etiology of bipolar disorder (BD), the role of such interactions is unknown. Here, we tested whether trauma during childhood could modify the effect of two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) in terms of susceptibility to BD. The study enrolled 878 Caucasian young adults in a cross-sectional population-based survey. BD diagnosis was performed using a clinical interview MINI 5.0, and trauma was assessed with the childhood trauma questionnaire (CTQ). Binary logistic regression models were employed to test the main effects of polymorphisms, haplotypes, and GxE interactions using sex as a confounder. We did not observe an association between the polymorphisms and diagnosis of BD. However, we noted that childhood trauma modified the effect of the rs4765913 polymorphism (p = .018) and the AA haplotype (rs1006737 - rs4765913) (p = .018) on BD susceptibility. A allele carriers of the rs4765913 polymorphism or the AA haplotype exposed to childhood trauma are more likely to develop BD compared to the individuals without a genetic risk. Thus, this study showed that the risk of developing BD in individuals exposed to childhood trauma was influenced by the individual's genetic background, varying according to the CACNA1C genotypes.

GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and lead to the production of aggregating dipeptide repeat proteins (DPRs) via repeat associated non-AUG (RAN) translation. Here, we show the similar intronic GGCCTG HREs that causes spinocerebellar ataxia type 36 (SCA36) is also translated into DPRs, including poly(GP) and poly(PR). We demonstrate that poly(GP) is more abundant in SCA36 compared to c9ALS/FTD patient tissue due to canonical AUG-mediated translation from intron-retained GGCCTG repeat RNAs. However, the frequency of the antisense RAN translation product poly(PR) is comparable between c9ALS/FTD and SCA36 patient samples. Interestingly, in SCA36 patient tissue, poly(GP) exists as a soluble species, and no TDP-43 pathology is present. We show that aggregate-prone chimeric DPR (cDPR) species underlie the divergent DPR pathology between c9ALS/FTD and SCA36. These findings reveal key differences in translation, solubility, and protein aggregation of DPRs between c9ALS/FTD and SCA36.

Major depressive disorder (MDD) is a disease that severely impairs psychosocial functioning and decreases the subject's quality of life. Patients who received psychotherapy have a better long-term therapeutic response than those who have only been treated with antidepressants or have not been treated. There are few studies in the literature that follow the outcomes of psychotherapeutic treatments for depression for more than two years. The aim of this study is to compare the therapeutic response of two models of brief psychotherapy for MDD treatment (Cognitive Behavioral Therapy and Short-term Psychodynamic Psychotherapy) with naturalistic controls who received treatment as usual in a three-year follow-up. This is a sample of 75 outpatients, mostly women (82.7%), with a median age of 33 (27-44). The interventions took place in 50-minute sessions once a week for 14 to 16 weeks. Outcomes were assessed at baseline and three years after the intervention. Regarding depressive symptoms, the therapeutic response was maintained three years after the conclusion of the brief models of psychotherapy. Functional capacity long-term maintenance depended not only on the intervention but also on the education level, the work situation and the severity of depressive symptoms at the beginning of the treatment.

Aim We aimed to identify whether lifetime cocaine use is a risk factor for conversion from major depressive disorder (MDD) to bipolar disorder (BD) in an outpatient sample of adults. Methods This prospective cohort study included 585 subjects aged 18 to 60 years who had been diagnosed with MDD as assessed by the Mini International Neuropsychiatric Interview (MINI-Plus) at baseline (2012-2015). Subjects were reassessed a mean of 3 years later (2017-2018) for potential conversion to BD as assessed by the MINI-Plus. Lifetime cocaine use was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test. Results In the second wave, we had 117 (20%) losses, and 468 patients were reassessed. The rate of conversion from MDD to BD in 3 years was 12.4% (n = 58). A logistic regression analysis showed that the risk for conversion from MDD to BD was 3.41-fold higher (95% confidence interval, 1.11-10.43) in subjects who reported lifetime cocaine use at baseline as compared to individuals who did not report lifetime cocaine use at baseline, after adjusting for demographic and clinical confounders. Conclusion These findings showed that lifetime cocaine use is a potential predictor of conversion to BD in an MDD cohort. Further studies are needed to assess the possible underlying mechanisms linking exposure to cocaine with BD conversion.

Introduction Mental health assessment in childhood needs to be carried out within a broader context that includes different factors. Objective To assess the prevalence of emotional and behavioral problems in schoolchildren and associated factors. Method A cross-sectional study was conducted with a school-based sample at 20 schools selected by systematic random sampling. Participants consisted of children aged 7-8 year old and their parents or primary caregivers. The Strengths and Difficulties Questionnaire (SDQ) was used to screen for the presence of emotional and behavioral problems in children. Results A total of 596 dyads were evaluated. The prevalence of emotional and behavioral problems was 30.0% among boys and 28.2% among girls. Hyperactivity/inattention were more prevalent among boys (p=0.015). Belonging to economically disadvantaged strata increased the likelihood of emotional and behavioral problems among schoolchildren by 71% (p=0.001), while having parents or caregivers with mental disorder increased by 2.2 times that probability (p

To assess circadian preference among a community sample of people with bipolar disorder, major depression and without any mood disorders. Secondly, we investigated the association of circadian preference with cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and, tumor necrosis factor alpha (TNF-α) and oxidative stress assessed by thiobarbituric acid reactive substances (TBARS), uric acid and Protein Carbonyl Content (PCC).A cross-sectional study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. A sample of 215 participants, in whom we measured circadian preferences, IL-6, IL-10, TNF-α, TBARS, uric acid, PCC. Biological rhythms were evaluated using the Biological Interview of Assessment in Neuropsychiatry.Bipolar group presented a higher alteration in biological rhythms (40.40±9.78) when compared with the major depression group (36.35±9.18) and control group (27.61±6.89) p0.001. Subjects with bipolar disorder who were active at night and had a day/night cycle reverse showed decreased levels of IL-6 (t, 44=2.096; p=0.042), (t, 44=2.213; p=0.032), respectively. In the bipolar disorder group subjects who presented day/night cycle reverse had lower TBARS levels (t, 41=2.612; p=0.013). TNF-α were decreased in subjects more active at night with bipolar disorder.Lower serum levels of IL-6, TNF-α and TBARS were associated with evening preference in bipolar disorder group. These findings suggest that chronotype may alter the levels of interleukins and oxidative stress levels in bipolar and healthy subjects. A better understanding of the role of circadian preferences in levels of interleukins and oxidative stress are needed.

The purpose of this study was to assess the disruption in biological rhythms and metabolic syndrome (MetS) in individuals with depressive episode. This was a cross-sectional, population-based study with a representative sample of 905 young adults. Current depressive episode were confirmed by a psychologist using the Mini International Neuropsychiatric Interview (MINI)-Plus. Self-reported biological rhythms were assessed using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). MetS was defined using modified NCEP/ATPIII criteria. Significant main effects of current depressive episode (p

Background Cognitive impairment is a well-established feature of bipolar disorder (BD). Comorbid BD and substance use leads to poor psychosocial and clinical outcomes. However, knowledge on the neurocognitive functioning of individuals with dual diagnosis is limited. The aim of this study is to assess the cognitive performance of subjects with BD, BD with comorbid alcohol use disorder (AUD), and BD with comorbid illicit substance use disorders (SUD) as compared to healthy individuals. Methods We included 270 inpatients and outpatients with BD and 211 healthy controls. The diagnostic of BD and substance use disorder was assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis I. Demographic and clinical information were also collected. The cognitive assessment included the Wechsler Test of Adult Reading (WTAR), and a revised version of the California Verbal Learning Test (CVLT) as part of the South Texas Assessment of Neurocognition (STAN). Results The STAN was administered to 134 BD patients (100 female, M±SD: 37.37±12.74 years), 72 BD patients with AUD (40 female, M±SD: 38.42±11.82), 64 BD patients with SUD (39 female, M±SD: 34.50±10.57), and 211 healthy controls with no lifetime history of mental illness and substance use (127 female, M±SD: 34.80±12.57 years). In terms of clinical characteristics, BD+SUD showed a marginally earlier onset of illness compared to BD. Compared to HC, BD performed poorly in the immediate recall and short-delay free tests of the CVLT, while BD patients with AUD and SUD showed significant memory deficits in both the immediate recall and recognition components of the CVLT. There were no differences in memory performance between BD and BD with either AUD or SUD. Conclusions A history of substance use disorders is associated with an earlier onset of BD. BD has marked effects on processes underlying the encoding of new information, while comorbid substance use in BD impairs more specifically the recognition of previously presented information. Future longitudinal studies should evaluate the effects of AUD and SUD on illness progression and therapeutic outcomes.

Depression is a serious condition that is associated with great psychic suffering and major impairments on the patient's general health, quality of life, and social and occupational activities. In some cases, it may lead to suicide. Regardless of the innumerous research works that have already addressed depression in wide and specific facets, there is still a lot to grasp in order to effectively help preventing and treating depression. This work presents data from a randomized clinical trial that sought to evaluate the effectiveness of two brief psychotherapeutic for Depression: Cognitive Behavioral Therapy (CBT) and Supportive-Expressive Dynamic Psychotherapy (SEDP). This was a convenience sample composed of 46 individuals that were evaluated using a structured diagnostic interview and then randomly allocated to the SEDP group. We examined baseline and post-intervention serum levels of the Interleukin-6 (IL-6) and the Tumor Necrosis Factor (TNF-α) in addition to the severity of depressive symptoms according to the Outcome Questionnaire - 45.2 (OQ-45.2) and the Beck Depression Inventory (BDI). Results show that serum IL-6 and TNF-α levels, as well as the scores from the OQ-45.2 and the BDI significantly decreased after 16 sessions of SEDP (p < 0.001), except for the Interpersonal Relationship domain from the OQ-45. Despite the reduction of serum cytokines levels and OQ-45 and BDI scores, they were only significantly correlated regarding the social role domain from the OQ-45. Nonetheless, our data suggests an effective role of brief psychodynamic psychotherapy in the reduction of depressive symptoms and serum inflammatory levels that are associated with depression.

Aim: To evaluate the impact of psychoeducational intervention on the levels of burden, of self-esteem and quality of life in caregivers of patients diagnosed with Bipolar Disorders. Method: In this randomized clinical trial, changes in degree of burden, levels of self-esteem and quality of life were evaluated. Caregivers could participate in the group of psychoeducation (six sessions) or usual treatment (without psychoeducation following a manual). Results: There were no significant differences regarding levels of objective burden between groups. Both groups presented improvement in subjective burden scores throughout the interventions. Objective burden scores showed significant reduction in the usual treatment group ( p = .003) and a trend toward decrease in the psychoeducational intervention ( p = .081). There are no differences regarding improvement in perceived self-esteem and quality of life when comparing means between the groups with and without intervention. Conclusion: A six-session caregiver psychoeducational intervention on bipolar disorder did not bring benefits to caregiver’s health. A longer longitudinal follow-up study would be crucial to see whether there were differences in degree of burden, perceived self-esteem and quality of life over time in caregivers.

Children with cerebral palsy (CP) often present aberrant hip geometry, more specifically increased femoral anteversion and neck-shaft angle. Furthermore, altered gait patterns are present within this population. This study analyzed the effect of aberrant femoral geometry, as present in subjects with CP, on muscle control of pelvis orientation, hip and knee joint kinematics. We ran dynamic simulations of CP and normal gait using two musculoskeletal models, one reflecting normal femoral geometry and one reflecting proximal femoral deformities. The results show that the combination of aberrant bone geometry and CP-specific gait characteristics beneficially increased the potentials of gluteus medius and maximus to control the hip and knee extension. In contrast, the potentials of the hamstrings to extend the hip decreased but to flex the knee increased. In conclusion, this study emphasizes the concomitant effect of the presence of proximal femoral deformity and CP gait characteristics on the muscle control of pelvis orientation and hip and knee joint kinematics during single stance. Not accounting for subject-specific geometry will affect the calculated muscles’ potential during gait. Therefore, the use of generic models to assess muscle function in the presence of femoral deformity and CP gait should be treated with caution. publisher: Elsevier articletitle: The role of altered proximal femoral geometry in impaired pelvis stability and hip control during CP gait: A simulation study journaltitle: Gait & Posture articlelink: http://dx.doi.org/10.1016/j.gaitpost.2015.11.010 content_type: article copyright: Copyright © 2015 Elsevier B.V. All rights reserved. ispartof: Gait & Posture vol:44 pages:61-67 ispartof: location:England status: published

Objective To assess the prevalence of childhood trauma and types of trauma on mood disorders among young adults in a population-based sample. We further gathered data on family history of mood disorders to test the hypothesis that childhood trauma is a mediating factor for the association between family history of mood disorder and mood disorder in adulthood. Method This is a cross-sectional study, including young adults with bipolar disorder, major depressive disorder, and matched controls without any mood disorder. Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). The Hicks and Tingley implementation was employed to assess whether trauma is a mediator of the effect of family history on diagnosis of any mood disorder. Results All types of trauma were associated with both major depression and bipolar disorder, with the exception of sexual abuse, which was only associated with bipolar disorder. Moreover, family history of psychiatric illness was also associated with mood disorder in adulthood and with childhood trauma. Using the presence of any mood disorder as the outcome, a third of the effect of having any family history of mood disorder was mediated via childhood trauma. Conclusion This investigation provides further support, in a population-based sample of young adults, of the association between childhood trauma and mood disorders, with sexual abuse being specifically linked with bipolar disorder. The hypothesis that childhood trauma would function as a partial mediator of the association between family history of mood disorder and mood disorder in adulthood was also confirmed.

Background Cocaine abuse is capable of activating the innate immune system in the CNS resulting in deregulation of homeostasis between pro and antiinflammatory cytokines. The aim of this study was to investigate serum levels of pro and antiinflammatory cytokines, IL-6 and IL-10 respectively, in cocaine users from a young population-based sample. Methods This is a case–control study nested in a cross-sectional population-based survey, with individuals of 18 and 35 years old. Two groups were selected: 24 healthy controls and 12 subjects who reported cocaine use. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. Results There was a statistically significant increase in IL-6 (p = 0.037) and decrease in IL-10 (p = 0.007) serum levels, between cocaine users and the control group. There was also an increase in the ratio IL-6/IL-10 (p = 0.013) among cocaine users individuals, when compared to the control group. Conclusions Our results suggest that cocaine users showed an activation of the immune system when compared a control group, demonstrating a disruption in the balance of pro and antiinflammatory cytokines. Thus, peripheral cytokines may represent a putative biomarkers for cocaine users, contributing to the development of diagnosis and effective treatments.

Objectives Although clinical evidence suggests important differences between unipolar mania and bipolar-I disorder (BP-I), epidemiological data are limited. Combining data from nine population-based studies, we compared subjects with mania (M) or mania with mild depression (Md) to those with BP-I with both manic and depressive episodes with respect to demographic and clinical characteristics in order to highlight differences. Methods Participants were compared for gender, age, age at onset of mania, psychiatric comorbidity, temperament, and family history of mental disorders. Generalized linear mixed models with adjustment for sex and age as well as for each study source were applied. Analyses were performed for the pooled adult and adolescent samples, separately. Results Within the included cohorts, 109 adults and 195 adolescents were diagnosed with M/Md and 323 adults and 182 adolescents with BP-I. In both adult and adolescent samples, there was a male preponderance in M/Md, whereas lifetime generalized anxiety and/panic disorders and suicide attempts were less common in M/Md than in BP-I. Furthermore, adults with mania revealed bulimia/binge eating and drug use disorders less frequently than those with BP-I. Conclusions The significant differences found in gender and comorbidity between mania and BP-I suggest that unipolar mania, despite its low prevalence, should be established as a separate diagnosis both for clinical and research purposes. In clinical settings, the rarer occurrence of suicide attempts, anxiety, and drug use disorders among individuals with unipolar mania may facilitate successful treatment of the disorder and lead to a more favorable course than that of BP-I disorder.

Objective The aim of this study was to assess if cytokines levels (IL-6 and IL-10) are related to major depressive disorder (MDD) and bipolar disorder (BD), in a population-based study. Methods This was a cross-sectional study population-based, involving 1037 people aged 18–35. MDD, BD, anxiety and suicide risk were assessed using the Mini International Neuropsychiatric Interview. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. Results The total sample comprised 1034 young adults, being 14.4% with MDD and 13.7% with BD. MDD and BD groups showed significantly higher serum IL-6 levels (p ≤ 0.001) and IL-10 levels (p ≤ 0.001) when compared to healthy control group. No correlation was found between serum IL-6 and IL-10 levels in health control group (p = 0.830; r = − 0.008), non-suicide risk (p = 0.337; r = 0.032) and non-anxiety disorder (p = 0.375; r = 0.031). Covariance analysis showed that mood disorders alone, increase both interleukin levels (IL-6, p = 0.019; and IL-10, p = 0.026), whilst the interaction of mood disorders and suicide risk or anxiety disorders did not. Conclusion Our results suggest that inflammatory dysregulation may be involved in the physiopathology of mood disorders and serum IL-6 and IL-10 levels are putative biomarkers for these disorders.

Aim The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. Methods This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. Results We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. Conclusion Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.

The aim of this study was to evaluate the effect of two brief psychotherapy models for major depressive disorder (MDD). This is a randomized clinical trial with 247 individuals diagnosed with MDD. Supportive-expressive dynamic psychotherapy (SEDP) (18 sessions) and cognitive-behavioral therapy (CBT) (16 sessions) were the two models used in this study. Participants were evaluated at baseline, during treatment, and postintervention (last session). Clinically significant changes were found in both psychotherapy models, and CBT showed higher response rates. Regarding the Beck Depression Inventory-II [F(1,120) = 4.07, p = 0.046] and Outcome Questionnaire 45.2 [F(1.114) = 7.99, p = 0.006], CBT had a better effect than SEDP. Hence, the results obtained have contributed to literature, served to corroborate the importance and effectiveness of psychodynamic psychotherapy, as well as explored the mechanisms of change, remission, and response in the treatment of MDD, which have been ignored to a large extent.

The present study aimed to verify the association between maternal depression and emotional and behavioral problems in school children in Pelotas, Southern Brazil, considering that maternal depression increases children's vulnerability for developing psychiatric disorders. This is a cross-sectional study with a school-based sample conducted between August 2015 and November 2016 and it is part of a major project entitled 'Healthy Childhood in Context: A Multidisciplinary Investigation'. Schoolchildren aged between 7 and 8 years and one of their respective parents or a primary caregiver were included in the study. Maternal depression was assessed using the Mini International Neuropsychiatric Interview (MINI). The presence of emotional and behavioral problems in children was verified by the Strengths and Difficulties Questionnaire (SDQ) - parents version. Children of depressed mothers exhibited higher mean scores in all SDQ domains and in the total score when compared to children of non-depressed mothers. Lower socio-economic status was also associated with higher SDQ scores. Our results showed the effects of both maternal depression and poverty on children emotional and behavioral problems, which evidence the need for child mental health preventive care, and free quality assistance for both mothers and their children.

Objective Salivary cortisol levels and biological rhythms could be hypothesized as part of the multifactorial framework that explains bruxism etiology. The objective of this study was to examine salivary cortisol levels and biological rhythms in schoolchildren with sleep bruxism (SB). Methods This is a cross-sectional study with a school-based sample. The Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids (BRIAN-K) was used to evaluate biological rhythms. Salivary samples were collected by the spitting method. The salivary cortisol level was measured by electrochemiluminescence. The criteria proposed by the American Academy of Sleep Medicine (AASM) were used to evaluate SB. Results The SB prevalence was 16%. The SB presence was associated with belonging to families of lower economic status (p = 0.003). In addition, children with SB showed greater difficulty in maintaining biological rhythm (p = 0.002) and had higher levels of salivary cortisol (p = 0.034) compared with children without SB. Conclusions Higher levels of cortisol and disruption of biological rhythm was associated with SB in schoolchildren.

Childhood trauma is a complex experience, much reported by subjects with bipolar disorder. There are still few studies that assess its consequences in a community sample of bipolar in early stage. The aim of the present study is to assess the association between childhood trauma and clinical outcomes, including the global functioning, in a community sample of young adults with bipolar disorder. This is a cross-sectional study with a community sample of subjects with bipolar disorder, from 23 to 30 years old, with and without childhood trauma. The trauma experiences during childhood were assessed by Childhood Trauma Questionnaire (CTQ). The functioning was assessed by Functioning Assessment Short Test (FAST). Ninety subjects with bipolar disorder were included in the study (30 with childhood trauma and 60 without childhood trauma). Young adults with bipolar disorder and childhood trauma showed higher prevalence of current suicide risk, higher severity of depressive symptoms, and higher functioning impairment as compared to subjects with bipolar disorder without childhood trauma. The childhood trauma experiences appear to be an environmental risk factor for worse clinical outcomes and higher functional impairment.

Objective: To correlate neurotrophic factors – brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) – and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

Background:Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like theC9orf72‘GGGGCC’ (G4C2) repeat that causes approximately 5-7% of all amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases, are too long to sequence using short-read sequencing technologies. It is unclear whether long-read sequencing technologies can traverse these long, challenging repeat expansions. Here, we demonstrate that two long-read sequencing technologies, Pacific Biosciences’ (PacBio) and Oxford Nanopore Technologies’ (ONT), can sequence through disease-causing repeats cloned into plasmids, including the FTD/ALS-causing G4C2repeat expansion. We also report the first long-read sequencing data characterizing theC9orf72G4C2repeat expansion at the nucleotide level in two symptomatic expansion carriers using PacBio whole-genome sequencing and a no-amplification (No-Amp) targeted approach based on CRISPR/Cas9.Results:Both the PacBio and ONT platforms successfully sequenced through the repeat expansions in plasmids. Throughput on the MinlON was a challenge for whole-genome sequencing; we were unable to attain reads covering the humanC9orf72repeat expansion using 15 flow cells. We obtained 8x coverage across theC9orf72locus using the PacBio Sequel, accurately reporting the unexpanded allele at eight repeats, and reading through the entire expansion with 1324 repeats (7941 nucleotides). Using the No-Amp targeted approach, we attained >800x coverage and were able to identify the unexpanded allele, closely estimate expansion size, and assess nucleotide content in a single experiment. We estimate the individual’s repeat region was >99% G4C2content, though we cannot rule out small interruptions.Conclusions:Our findings indicate that long-read sequencing is well suited to characterizing known repeat expansions, and for discovering new disease-causing, disease-modifying, or risk-modifying repeat expansions that have gone undetected with conventional short-read sequencing. The PacBio No-Amp targeted approach may have future potential in clinical and genetic counseling environments. Larger and deeper long-read sequencing studies inC9orf72expansion carriers will be important to determine heterogeneity and whether the repeats are interrupted by non-G4C2content, potentially mitigating or modifying disease course or age of onset, as interruptions are known to do in other repeat-expansion disorders. These results have broad implications across all diseases where the genetic etiology remains unclear.

Objective: To evaluate the serum leptin levels in cannabis smokers. Methods: This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit. Results: Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008). When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039). Conclusion: Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.