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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.

Motivation: Bipolar disorder (BD) and schizophrenia (SZ) has a difficult diagnosis, so the main objective of this article is to propose the use of Artificial Neural Networks (ANNs) to classify (diagnose) groups of patients with BD or SZ from a control group using sociodemographic and biochemical variables. Methods: Artificial neural networks are used as classifying tool. The data from this study were obtained from the array collection from Stanley Neuropathology Consortium databank. Inflammatory markers and characteristics of the sampled population were the inputs variables. Results: Our findings suggest that an artificial neural network could be trained with more than 90% accuracy, aiming the classification and diagnosis of bipolar, schizophrenia and control healthy group. Conclusion: Trained ANNs could be used to improve diagnosis in Schizophrenia and Bipolar disorders.

Resumo Avaliar a satisfação profissional e a sobrecarga de trabalho dos enfermeiros atuantes em serviços de saúde mental e realizar uma comparação em relação aos demais profissionais do serviço. Estudo transversal, com amostragem por critério de conveniência, realizado em 2016 com 61 profissionais da área de saúde mental dos Centros de atenção psicossocial de um município localizado no extremo sul do Brasil. Para coleta de dados foi aplicado um questionário sociodemográfico e as Escalas de avaliação do impacto do trabalho (Impacto-Br) e de satisfação da equipe (Satis-Br). A análise dos dados foi realizada através do programa SPSS 21.0.O nível de sobrecarga global dos enfermeiros foi de 2,92 ± 0,42 e de satisfação global de 3,38 ± 0,51. Quando avaliado os escores na escala Satis-Br, houve uma diminuição estatisticamente significativa nos níveis de satisfação dos enfermeiros (3,36 ± 0,77) em relação aos demais profissionais atuantes no serviço (3,78 ± 0,56) no escore qualidade dos serviços oferecido (p = 0,04). O fator que promoveu maior nível de sobrecarga de trabalho entre os enfermeiros estão relacionados ao sentimento de se sentir fisicamente cansado (2,99 ± 0,92). Já o fator que promoveu maior satisfação profissional está relacionado ao bom relacionamento com a equipe (4,06 ± 0,65). Abstract This study assessed job satisfaction and work overload among doctors, nurses, psychologists, and nursing technicians working in community mental health services and conducted a comparison between nurses and other healthcare professionals. Using convenience sampling, a cross-sectional study was conducted with 61 healthcare professionals working in psychosocial care centers in a municipality located in the South Region of Brazil. Data was collected using a sociodemographic questionnaire, work impact assessment scale (Impacto - Br), and mental health professional satisfaction scale (Satis - Br). Data analysis was performed using the statistical software package SPSS 21.0. The average overall work overload score of nurses was 2.92 ± 0.42 and the average overall job satisfaction score was 3.38 ± 0.51. The level of satisfaction of nurses with the quality of services provided was lower than that of other professionals (3.36 ± 0.77 compared to 3.78 ± 0.56, respectively; p = 0.04). The factor that had the greatest negative influence on work overload among nurses was feeling physically tired (2.99 ± 0.92), while the factor that had the greatest positive influence on job satisfaction was good working relationships (4.06 ± 0.65).

Objective Postoperative cognitive dysfunction (POCD) may be related to brain injury. S100B protein and neuron-specific enolase (NSE) have been investigated as potential biochemical markers of neural cell injury in animals and humans. This study aimed to investigate the association between POCD, brain injury and serum concentrations of S100B and NSE after periodontal surgery in aged dogs. Study design Prospective observational animal study. Animals A total of 24 male and female dogs undergoing periodontal surgery. Methods Dogs were separated into two groups based on age: control group, 10 dogs ≤ 8 years and aged group, 14 dogs > 8 years. Cognitive function was measured preoperatively and on the seventh postoperative day using the Canine Cognitive Dysfunction Rating scale and the Age-Related Cognitive and Affective Disorders scale. S100B protein and NSE serum concentrations were measured before and immediately after the surgery. Results POCD was not observed after surgery in the present study. Serum concentrations of S100B and NSE were increased postoperatively in the control group but not in the aged group (p = 0.04 and 0.03, respectively). Preoperative S100B serum concentrations were significantly higher in the aged group (p = 0.01). Conclusions There was no association between POCD and high concentrations of S100B and NSE in dogs. However, increased postoperative serum concentrations of S100B and NSE were found in the control group after surgery, an effect that may indicate neural damage. Clinical relevance The results suggest that anesthesia and oral surgery are associated with higher postoperative serum concentrations of S100B and NSE in dogs ≤ 8 years old, which may indicate neural damage. Serum concentrations of S100B were elevated in aged dogs before anesthesia, a finding that might be related to chronic preoperative brain damage.

Fanny Helena Martins Salles,1 Pedro San Martin Soares,1 Carolina David Wiener,1 Thaise Campos Mondin,1 Paula Moraes da Silva,1 Karen Jansen,1–3 Luciano Dias de Mattos Souza,1 Ricardo Azevedo da Silva,1 Jean Pierre Oses1–3 1Translational Science on Brain Disorders, Department of Health and Behavior, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Translational Psychiatry Program, 3Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, USA Abstract: Nerve growth factor (NGF) is an important member of the neurotrophin family and its alteration has been associated with psychiatric disorders. Functionality consists of the activities that an individual can perform, as well as their social participation, which is an important factor in analyzing the carrier living conditions of subjects with psychiatric suffering. Several studies have evaluated functionality in bipolar disorder; however, no studies have evaluated the functionality in other mental disorders. There are also few studies investigating the association between functionality and the biological bases of mental disorders. This study aimed to evaluate the serum NGF levels in psychiatric patients and to verify a possible association between the serum neurotrophic levels and functionality. This was a cross-sectional study with a convenient sample obtained from the Public Mental Health Service from the south of Brazil. The final sample was composed of 286 patients enrolled from July 2013 to October 2014. Data was collected using a sociodemographic questionnaire, and the diagnosis was confirmed using the Mini International Neuropsychiatric Interview (M.I.N.I) and a Functioning Assessment Short Test. The serum NGF levels were determined using the enzyme-linked immunosorbent assay method. Statistical analyses were performed using IBM SPSS Statistic 21.0 software. NGF serum levels were increased significantly in patients with obsessive–compulsive disorder compared with patients with no obsessive–compulsive disorder (P=0.015). An increase in serum NGF levels in generalized anxiety disorder patients was observed compared with patients with no generalized anxiety disorder (P=0.047). NGF was negatively associated with autonomy (P=0.024, r=–0.136), work (P=0.040, r=–0.124), and cognition (P=0.024, r=–0.137), thereby showing that changes in serum levels of NGF are associated with functionality in mental disorders. Keywords: NGF, mental disorders, functional impairment

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.

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 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.

Resumo O objetivo do estudo foi mensurar a prevalência e os fatores associados à prática de atividade física de lazer, bem como verificar a associação desta com o uso de substâncias lícitas em uma amostra populacional de adultos jovens. Estudo transversal de base populacional com adultos jovens de 18 a 35 anos de idade, residentes da zona urbana da cidade de Pelotas-RS (Brasil). A seleção amostral foi realizada por conglomerados, sendo constituída por 1953 indivíduos, dentre 82 setores censitários sorteados. A prática de atividade física foi avaliada por meio do Questionário Internacional de Atividade Física (IPAQ). Para a análise estatística utilizou-se a regressão de Poisson. A prevalência de jovens ativos em atividade física de lazer foi de 25,3% e esteve associada a ser do sexo masculino, ter entre 18 e 23 anos de idade, pertencer ao maior tercil do indicador econômico nacional e não fazer uso diário de tabaco. Sabendo-se da importância da atividade física de lazer para a saúde, os incentivos para esta prática devem ser focados nos grupos de mulheres, de maior idade, de estratos econômicos inferiores e que fazem uso de tabaco.

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.

Objective The aim of this study was to evaluate the effect of childhood trauma in cytokine serum levels of individuals with MDD. Methods This was a cross-sectional study population-based, with people aged 18 to 35. The Mini International Neuropsychiatric Interview (M.I.N.I) measured to current major depressive disorder (MDD). To evaluate traumatic experiences during childhood, the Childhood Trauma Questionnaire (CTQ) was applied. Serum TNF- α, IL-6 and IL-10 levels were measured by ELISA using a commercial kit. Results The total sample comprised 166 young adults, of these: 40.4% were subjects with MDD and childhood trauma and 59.6% were diagnosed with MDD without childhood trauma. In relation to serum interleukin levels, subjects with childhood trauma showed a significantly higher serum IL-6 (p = 0.013) and IL-10 levels (p = 0.022) to compare no childhood trauma. Subjects with childhood trauma was observed positive correlation between serum IL-6 and physical abuse (r = 0.232, p = 0.035) and emotional abuse (r = 0.460, p ≤ 0.001). Moreover, IL-10 were positive correlation with physical abuse (r = 0.258, p = 0.013). TNF- α was not associated with childhood trauma. Conclusion Childhood maltreatment may result higher inflammation dysregulation in individuals with depression than individuals that no has childhood maltreatment.

Objective: To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. Methods: This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores ≥ 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). Results: Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. Conclusion: These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.

BACKGROUND: Postoperative cognitive dysfunction (POCD) may be related to the systemic inflammatory response and an increase in serum markers of brain injury such as S100B protein and neuron-specific enolase (NSE). OBJECTIVE: The study aims to evaluate the association between POCD and serum levels of S100B and NSE after coronary artery bypass grafting surgery (CABG). DESIGN: Prospective observational study. SETTING: Single university teaching hospital. PATIENTS: We investigated 88 patients undergoing CABG. MAIN OUTCOMES MEASURES: Cognitive function was measured preoperatively, and at the 21st and 180th postoperative days (i.e. 6 months after surgery). S100B protein and NSE serum levels were evaluated preoperatively, after induction of anaesthesia, at the end of surgery and at 6 and 24 h after surgery. RESULTS: The incidence of POCD was 26.1% at 21 days after surgery and 22.7% at 6 months after surgery. Increased serum levels of S100B protein and NSE were observed postoperatively and may indicate brain damage. CONCLUSION: Although serum levels of S100B protein and NSE are both significantly increased postoperatively, our findings indicate that serum levels of S100B protein may be more accurate than NSE in the detection of POCD after CABG.

CONTEXTO: A depressão é um importante problema de saúde global e vem causando impacto negativo na vida dos indivíduos e na de suas famílias, além de elevar a demanda dos serviços de saúde. OBJETIVO: Verificar a prevalência de depressão e de fatores associados em indivíduos com idade superior a 14 anos que buscaram atendimento na atenção primária. MÉTODOS: Estudo transversal em três Unidades Básicas de Saúde vinculadas à Universidade Católica de Pelotas. A depressão, os transtornos de ansiedade e o risco de suicídio foram avaliados por meio da Mini International Neuropsychiatric Interview (MINI), enquanto os fatores associados, como idade, gênero, vive ou não com o/a companheiro/a, escolaridade e uso de substâncias psicoativas, foram avaliados por meio de questionário sociodemográfico. RESULTADOS: A prevalência de depressão foi de 23,9% (n = 256), apresentando-se mais evidente nas mulheres, com 4 a 7 anos de escolaridade, de classe socioeconômica D ou E, que abusam ou são dependentes de álcool, com algum transtorno de ansiedade e com risco de suicídio (p < 0,050). CONCLUSÃO: Diante de tais resultados, salientamos a inserção de cuidados em saúde mental por meio de avaliações diagnósticas e de protocolos de atendimento que abarquem a depressão e suas comorbidades na atenção primária.BACKGROUND: Depression, an important global health problem, negatively impacts the lives of individuals and their families beyond simply increasing the demand for health services. OBJECTIVE: To assess the prevalence of depression and associated mental health issues in individuals older than 14 years of age seeking primary care. METHODS: A cross-sectional study was conducted in three primary care units involved with the Catholic University of Pelotas. Depression, anxiety disorders, and suicide risk were assessed using the Mini International Neuropsychiatric Interview (MINI). Factors such as age, gender, solitary living, education, and psychoactive substance use were evaluated using a sociodemographic questionnaire. RESULTS: The overall prevalence of depression was 23.9% (n = 256). Depression was more prevalent in women with only 4-7 years of education, in women who belong to socioeconomic class D or E, in those who abuse or are dependent on alcohol, or in women who showed an anxiety disorder or suicide risk (p < 0.050). DISCUSSION: Based on these findings, we emphasize the integration of mental health care into primary care through diagnostic evaluations and treatment protocols that cover depression and its comorbidities.

Background: Alcohol abuse is followed by neuroadaptive brain changes, in addition to inducing changes in the immune system. The objective of this study was to investigate the peripheral levels of proinflammatory (IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines, as well the inflammatory balance in relation to alcohol use in subjects from a young population-based sample. Methods: This is a cross-sectional study nested in a population-based study of people aged 18–35 years, involving 629 participants. The CAGE questionnaire was used to evaluate Alcohol Use Disorder, and CAGE scores ≥ 2 were considered a positive screen for alcohol use disorder. Serum levels of IL-6, IL-10 and TNF-α were measured by ELISA using a commercial kit. Results: There was as a statistically significant increase in IL-6 (p ≤ 0.001) and statistically significant decrease in IL-10 (p=0.017) serum levels in the Alcohol Use Disorder group when compared with subjects that did not abuse alcohol and that a CAGE score

The present study aimed to determine whether any gender-related difference exists concerning oxidative stress parameters in a population of 231 subjects, and if these changes might be related to gender-associated differences in major depressive disorder (MDD) or bipolar disorder (BD) vulnerability. This is a case-control nested in a population-based study. The initial psychopathology screen was performed with the Mini-International Neuropsychiatric Interview and the diagnostic was further confirmed with the Structured Clinical Interview for DSM-IV. Blood samples were obtained after the interview and the oxidative stress parameters such as uric acid, advanced oxidation protein product (PCC) and lipid hydroperoxides (TBARS) were determined. Our results indicated a higher prevalence of MDD and BD in women when compared to men. In addition, significant gender differences were found in the levels of PCC (0.27 ± 0.27 vs. 0.40 ± 0.31 nmol CO/mg protein, men vs. women, respectively; P = 0.02) and uric acid (4.88 ± 1.39 mg/dL vs. 3.53 ± 1.02 mg/dL, men vs. women, respectively; P = 0.0001), but not in TBARS (0.013 ± 0.01 nmol/mg of protein vs. 0.017 ± 0.02 nmol/mg of protein, men vs. women respectively; P = 0.243). After sample stratification by gender, no association was found between oxidative stress parameters and clinical diagnosis of MDD and BD for women (P = 0.516 for PCC; P = 0.620 for TBARS P = 0.727 for uric acid) and men (P = 0.367 for PCC; P = 0.372 for TBARS P = 0.664 for uric acid). In this study, women seem more susceptible to oxidative stress than male. However, these gender-based differences do not seem to provide a biochemical basis for the epidemiologic differences in mood disorders susceptibility between sexes.

CONTEXTO: A depressão é um importante problema de saúde global e vem causando impacto negativo na vida dos indivíduos e na de suas famílias, além de elevar a demanda dos serviços de saúde. OBJETIVO: Verificar a prevalência de depressão e de fatores associados em indivíduos com idade superior a 14 anos que buscaram atendimento na atenção primária. MÉTODOS: Estudo transversal em três Unidades Básicas de Saúde vinculadas à Universidade Católica de Pelotas. A depressão, os transtornos de ansiedade e o risco de suicídio foram avaliados por meio da Mini International Neuropsychiatric Interview (MINI), enquanto os fatores associados, como idade, gênero, vive ou não com o/a companheiro/a, escolaridade e uso de substâncias psicoativas, foram avaliados por meio de questionário sociodemográfico. RESULTADOS: A prevalência de depressão foi de 23,9% (n = 256), apresentando-se mais evidente nas mulheres, com 4 a 7 anos de escolaridade, de classe socioeconômica D ou E, que abusam ou são dependentes de álcool, com algum transtorno de ansiedade e com risco de suicídio (p < 0,050). CONCLUSÃO: Diante de tais resultados, salientamos a inserção de cuidados em saúde mental por meio de avaliações diagnósticas e de protocolos de atendimento que abarquem a depressão e suas comorbidades na atenção primária. BACKGROUND: Depression, an important global health problem, negatively impacts the lives of individuals and their families beyond simply increasing the demand for health services. OBJECTIVE: To assess the prevalence of depression and associated mental health issues in individuals older than 14 years of age seeking primary care. METHODS: A cross-sectional study was conducted in three primary care units involved with the Catholic University of Pelotas. Depression, anxiety disorders, and suicide risk were assessed using the Mini International Neuropsychiatric Interview (MINI). Factors such as age, gender, solitary living, education, and psychoactive substance use were evaluated using a sociodemographic questionnaire. RESULTS: The overall prevalence of depression was 23.9% (n = 256). Depression was more prevalent in women with only 4-7 years of education, in women who belong to socioeconomic class D or E, in those who abuse or are dependent on alcohol, or in women who showed an anxiety disorder or suicide risk (p < 0.050). DISCUSSION: Based on these findings, we emphasize the integration of mental health care into primary care through diagnostic evaluations and treatment protocols that cover depression and its comorbidities.

Major depressive disorder (MDD) is a debilitating disorder and its pathophysiology is associated with deregulation of the immune system. We investigated the changes in circulating levels of proinflammatory cytokines (specifically IL-6 and TNF-α) measured by the ELISA kit in two psychotherapeutic interventions for MDD: Narrative Cognitive Therapy (NCT) and Cognitive Behavioral Therapy (CBT). This is a randomized clinical trial including 97 individuals (18 to 29 years-old) with MDD. In CBT there was a significant difference in serum levels of IL-6 and TNF-α, therefore indicating that CBT was more effective than NCT on serum levels proinflammatory cytokines.