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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The relationship between obesity and suicide risk is still unclear with controversial research results. The aim of this study is to investigate the relationship between obesity and suicide risk for men and women in a population-based study of young adults. This is a cross-sectional population-based study that identified young adults between 18 and 35 years of age. Suicide risk was investigated through the structured clinical interview Mini. Weight and height were assessed, and participants were classified as normal-weight body mass index (BMI < 30) or obese (BMI > 30). The prevalence of obesity was of 19.9% of the total sample (n = 1953). Obesity was more prevalent among women and participants between 27 and 35 years of age. Suicide risk was present in 13.0% of the sample and more prevalent among women. In our study we found an association between obesity and suicide risk for women, but not for men. Obesity was associated with a higher prevalence of suicide risk in women. Given the strength of the relationship between BMI and suicide, identifying the mechanisms associated with obesity, especially for women, can lead to new insights into the prevention of suicide risk [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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.Trial Registration: NCT01550159. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine the prevalence of and factors associated with depression and stress with perceived quality of life and the salivary cortisol levels in Community Health Agent (CHA).Materials and MethodsCross-sectional descriptive study of CHAs in Pelotas-RS, Brazil. Data collection, including sociodemographic information and factors related to work and health. Beck Depression Inventory (BDI) II was used to assess depressive symptoms, Inventory of Stress Symptoms Lipp (ISSL) was used for the analysis of stress and the WHOQOL-BREF was used to investigate quality of life. Salivary cortisol was quantified via ELISA test.ResultsThe assessments showed that 71.0% are in a state of stress resistance, 30.5% were in the alert state of stress and 32.8% were in the stress state of exhaustion. Depressive episodes (BDI≥12) were observed in 28.2%. The environmental domain had the lowest score for quality of life. We observed significantly higher salivary cortisol levels in CHAs with less than 1 year of service and with the lowest quality of life scores in the environmental subsection.ConclusionA high prevalence of stress and depression was observed in this sample of CHAs. In addition, the worst levels of quality of life were identified in the environmental subsection. Cortisol levels corroborate these findings regarding quality of life within the environmental domain and began working less than a year previously. [ABSTRACT FROM PUBLISHER]

Background The diagnosis of alcohol use disorder is based on clinical signs and on the measurement of biological markers. However, these markers are neither sufficiently sensitive, nor specific enough, for determining the effects of alcohol abuse on the central nervous system. Serum neurotrophins are important regulators of neural survival, development, function, and plasticity and have been found to be reduced in alcohol use disorder. The aim of this study was to investigate the alterations in serum neurotrophin levels (brain-derived neurotrophic factor [ BDNF], glial-derived neurotrophic factor [ GDNF], and nerve growth factor [ NGF]) in alcohol use disorder in a young population, and thus possibly representing the early stages of the illness. Methods This is a cross-sectional study, nested in a population-based study of people aged 18 to 35, involving 795 participants. The participants responded to the CAGE questionnaire, and a CAGE score of ≥2 was considered to be a positive screen for the abuse/dependence or moderate to severe alcohol use disorder. Serum BDNF, GDNF, and NGF levels were measured by ELISA. Results In the CAGE ≥ 2 group, GDNF ( p ≤ 0.001) and NGF ( p ≤ 0.001) serum levels were significantly increased, and the BDNF elevation was near a statistical significance ( p = 0.068) when compared to the CAGE < 2 group. A significantly positive correlation was observed only in the CAGE ≥ 2 group for BDNF/ GDNF ( r = 0.37, p < 0.001) and GDNF/ NGF ( r = 0.84, p < 0.001) levels. The correlation between the NGF and BDNF levels was significantly positive in both groups ( r = 0.28, p < 0.001 for the CAGE < 2 group, and r = 0.30, p = 0.008 for the CAGE ≥ 2 group). Conclusions These results suggest that elevated neurotrophins are candidate markers for the early stages of alcohol misuse. [ABSTRACT FROM AUTHOR]

Recent studies have evaluated the role of brain-derived neurotrophic factor (BDNF) in mood disorders; however, little is known about alterations in nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). The aim of this study was to evaluate differences among serum neurotrophic factors (BDNF, NGF and GDNF) in depressed patients and healthy controls and to verify the association between serum neurotrophic levels and clinical characteristics in a young, depressed population stratified by gender. This is a cross-sectional study with depressed patients and population controls 18-29 years of age. The concentrations of neurotrophic factors were determined by the ELISA method. The diagnosis of depression and the duration of the disease were assessed by the Structured Clinical Interview according to the diagnostic and statistical manual of mental disorders. Depression severity was measured with the 17-item Hamilton Rating Scale for Depression, and the severity of anxiety symptoms was measured using the Hamilton Anxiety Rating Scale. Serum BDNF and GDNF were lower in major depressive disorder (MDD) patients compared to controls ( p ≤ 0.001). Serum NGF levels were higher in MDD patients versus controls ( p ≤ 0.001). BDNF was associated with the duration of disease only in women ( p = 0.005). GDNF was not associated with clinical characteristics in either gender. In women, NGF was associated with the severity of depressive symptoms ( p = 0.009), anxiety ( p = 0.011) and disease duration ( p = 0.005). NGF was associated with disease duration in men ( p = 0.026). Our results demonstrated that significant neurochemical differences in NGF and BDNF, but not in GDNF, were associated with the clinical features of MDD when patients were stratified by gender. [ABSTRACT FROM AUTHOR]

Background: Early adverse experiences are associated with increased risk of developing psychiatric disorders, although little is known about the neurobiological mediators involved. The mechanisms by which early environmental influences may mediate vulnerability in the development of offspring await further investigation. The present study correlated the NGF, BDNF, IL-6 and cortisol levels of mothers with postpartum affective disorders (PPAD) with infant development. Methods: A longitudinal study was performed with 152 pregnant women and their infants. Between 60 and 120 days after delivery, women were interviewed and provided biological samples for biochemical analysis, and the infants were examined for neurobiological-motor development. Results: Overall, the mothers' history of affective disorders, PPAD and anxiety disorder were associated with infant motor development. Using an adjusted linear regression analysis, PPAD (p = 0.049), maternal anxiety disorder (p = 0.043), NGF level (p = 0.034) and infant cortisol level (p = 0.013) were associated with infant motor development. Using a factorial analysis of primary components, two components were retained. The psychological factor was characterized by a positive loading of a history of affective disorder, PPAD and anxiety disorder. For the biological factor, infant cortisol adhered negatively with infant motor development, but NGF was positively associated. The psychological factor had a negative association, but the biological factor had a positive association with infant motor development. Conclusions: There are few studies that have focused on the relationship of biomarkers and infant neurodevelopment. Our study points that psychological and biological factors are associated with infant motor development, however the causal relationship between these factors is still to be defined. [ABSTRACT FROM AUTHOR]

Several biological factors have been recently related with major depression and bipolar disorder. The aim of our paper was to investigate the peripheral levels of the protein neuronal specific enolase (NSE), a putative marker of neuronal damage, comparing patients with major depressive disorder and bipolar disorder to control subjects. This is a case-control study nested in a cross-sectional population-based survey. Psychopathology screen was performed using the Mini-International Neuropsychiatric Interview 5.0 and blood samples were collected from 108 young adults. Three groups were selected, 36 healthy controls, 36 subjects with major depression disorder and 36 subjects with bipolar disorder. Serum levels of NSE significantly decreased ( p = 0.002) in major depression disorder (2.19 ± 1.78 ng/mL) and bipolar disorder subjects (2.53 ± 2.61 ng/mL) compared to the control group (3.55 ± 2.19 ng/mL). In conclusion, peripheral neuronal specific enolase may be a useful marker drug-naïve major depression disorder and bipolar disorder, but its pathophysiological significance and response to treatment should be further investigated. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) is the most common psychiatric complication observed in women after they give birth. Some women are particularly sensitive to hormonal changes, starting in early menarche, thus increasing their vulnerability to psychological stressing agents that are triggered by environmental and physiological factors throughout their lives. Decreased serum brain-derived neurotrophic factor (BDNF) levels have been associated to different neuropsychiatric conditions and BDNF has been considered as a candidate marker for such dysfunctions. The goal of this study was to compare the levels of BDNF between mothers who suffer from PPD and healthy control mothers as well as to searching for associations between BDNF levels and the severity of PPD. This is a case-control study including 36 mothers with PPD and 36 healthy control mothers. PPD was defined according to the Beck Depression Inventory (BDI). Serum BDNF was assayed with the sandwich ELISA method. Results: Serum levels of BDNF were significantly lower in women with PPD than in control mothers ( P ≤ 0.03). A significant negative correlation between BDI score and serum BDNF levels was observed ( P ≤ 0.02 and r = −0.29). Our study demonstrated that low BDNF levels are associated with PPD. This result point out to the potential usage of BDNF in the screening of PPD, which could promote early treatment and, therefore, reduce the burden to the PPD women and to the health system. [ABSTRACT FROM AUTHOR]

Low cognitive performance in school children may cause undesirable phenomena, such as stress. In the crude analysis, lower scores for Vocabulary ( I r i = -0.131; I P i = 0.002), Block Design ( I r i = -0.102; I P i = 0.017), and Similarity ( I r i = -0.201; I P i < 0.001), as well as for Verbal IQ ( I r i = -0.192; I P i < 0.001), Executive IQ ( I r i = -0.097; I P i < 0.001), and Total IQ ( I r i = -0.176; I P i < 0.001) were associated with higher salivary cortisol levels. There is a consensus in the literature that high cortisol levels affect neuronal activity in the hippocampus and prefrontal cortex, which are important brain areas for cognitive performance. [Extracted from the article]