BDNF Levels According to Variations in the CACNA1C Gene: Sex-Based Disparity.

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.

Interleukin-6 and Interleukin-10 in mood disorders: A population-based study.

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.

Metabolic syndrome, depression and anhedonia among young adults.

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.

Serum Biomarkers and Clinical Outcomes in Traumatic Spinal Cord Injury: Prospective Cohort Study.

BACKGROUND: A plethora of reactive cellular responses emerge immediately after a traumatic spinal cord injury (SCI) and may influence the patient's outcomes. We investigated whether serum concentrations of neuron-specific enolase, interleukin-6, glial-derived neurotrophic factor, and neurotrophic growth factor reflect the acute-phase responses to different etiologies of SCI and may serve as predictive biomarkers of neurologic and functional outcomes. METHODS: Fifty-two patients were admitted to the intensive care unit after SCI due to traffic accidents, falls, and firearm wounds and had blood samples collected within 48 hours and 7 days after SCI. Thirty-six healthy subjects with no history of SCI were included as controls. Neurologic and functional status was evaluated on the basis of American Spinal Injury Association and Functional Independence Measure scores over a period of 48 hours and 6 months after SCI. RESULTS: Serum NSE increased significantly 48 hours and 7 days after SCI compared with controls, while interleukin-6 increased only at 48 hours. In contrast, the neurotrophic growth factor level significantly decreased 48 hours and 7 days after SCI. Serum glial-derived neurotrophic factor level did not differ from control at any time point. Also, there was no significant difference in biomarker concentrations between the etiologies of SCI or the level of spinal injury. There were no correlations between biomarker levels at 48 hours with neurologic or functional outcomes 7 days and 6 months after SCI. CONCLUSIONS: Our results suggest expansive axonal damage coupled with an acute proinflammatory response after SCI. However, in our study biomarker concentration did not correlate with short- or long-term prognosis, such as survival rate or sensory and motor function.

Serum GDNF levels and anxiety disorders in a population-based study of young adults.

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.

Childhood trauma and increased peripheral cytokines in young adults with major depressive: Population-based study.

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.

Serum brain-derived neurotrophic factor levels in subjects with major depressive disorder with previous suicide attempt: A population-based study.

Major depressive disorders (MDD) and suicide are significant public health concerns. Recent studies have been demonstrated that alterations in Brain Derived Neurotrophic Factor (BDNF) can be associated with this psychiatric disorders, MDD and suicide. Thus, the aim of this study was to evaluate differences in serum levels in individuals with MDD and with or without suicide attempt (SA), from a population-based sample. This was a paired cross-sectional study nested in a population-based study. The psychopathology screen was performed with the Mini-International Neuropsychiatric Interview (MINI). The total population of the sample consisted of 147 subjects distributed in three groups: 49 healthy controls, 49 subjects with MDD and 49 subjects with MDD and SA (MDD + SA). The BDNF serum levels were significantly reduced in subjects with MDD and MDD + SA compared to the healthy controls. However, there were no significant differences between the MDD and MDD + SA groups with respect to BDNF serum levels. These results suggest that SA did not interfere in the serum levels of BDNF, indicating that this neurotrophin may be related to the diagnosis of MDD and not to suicide attempt.

Serum levels of interleukins IL-6 and IL-10 in individuals with posttraumatic stress disorder in a population-based sample.

To evaluate the serum levels of IL-6 and IL-10 anti-inflammatory interleukins in individuals with post-traumatic stress disorder (PTSD) in a population-based study. This is a paired study nested in a cross-sectional population-based study. All individuals who presented PTSD and did not present major depressive disorder, diagnostic by interview--Mini International Neuropsychiatric Interview were selected. From these, 41 healthy controls were matched by sex and age. Serum levels of IL-6 and IL-10 were measured by the ELISA, using commercial kits. The group of individuals with PTSD showed a significant increase in the serum levels of IL-6 and IL-10. Our results suggest that individuals with PTSD may present an activation of the immune system, which may lead to neuroinflammation.

Brief psychoeducation for bipolar disorder: Evaluation of trophic factors serum levels in young adults.

The aim of this study was to evaluate the impact of psychoeducation in serum levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18-29 years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However, there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing GDNF levels in a sample of young adults with bipolar disorder.

Inflammatory cytokines and functional impairment in drug-free subjects with mood disorder.

OBJECTIVE: To assess the association between peripheral levels of inflammatory cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major Depressive Disorder (MDD) and population controls. METHODS: This was a cross-sectional study with a matched sample of drug-free young adults with BD (n=48), MDD (n=48) and population controls (n=48). Mood disorder was confirmed by a certified psychologist using the Structured Clinical Interview for DSM-IV (SCID-I). Functional impairment was assessed using the Functional Assessment Short Test (FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. RESULTS: Peripheral levels of IL-6 and IL-10 were not significantly different between subjects with BD, MDD compared to controls. Higher levels of functional impairment were verified in subjects with BD and MDD compared to population controls (p≤0.001). In addition, IL-6 and IL-10 levels were positively correlated with functional impairment in subjects with BD (IL-6: r=0.349, p=0.016; and IL-10: r=0.351, p=0.016). CONCLUSION: Inflammatory dysregulation was associated with functional impairment among drug-free subjects with BD. This finding suggests that inflammatory dysregulation may be involved in the neuroprogression of BD.

Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode.

OBJECTIVE: To assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode. METHODS: This was a cross-sectional study with young adults aged 24-30 years old. Depressive episode (bipolar or unipolar) 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). RESULTS: The sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016). CONCLUSION: Metabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis.

Mental disorders, functional impairment, and nerve growth factor.

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.

Biological rhythms, metabolic syndrome and current depressive episode in a community sample.

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<0.001, η(2)=0.163) and MetS (p=0.001, η(2)=0.011) were observed on total BRIAN score. There was a significant interaction between depression and MetS in total biological rhythm scores (p=0.002, η(2)=0.011) as well as sleep (p=0.001, η(2)=0.016) and social domains (p<0.001, η(2)=0.014). In the depressive group, subjects with MetS had a higher disruption in total BRIAN scores (p=0.010), sleep domain (p=0.004), social domain (p=0.005) and in the eating pattern domain approached the level of significance (p=0.098), when compared to subjects with no MetS. The results of the present study showed that self-reported disruptions in biological rhythms are associated with key components of the MetS in community adults with MDD. The understanding of the complex interactions between biological rhythms, MetS and depression are important in the development of preventive and therapeutic strategies.

Neuron-specific enolase levels in drug-naïve young adults with major depressive disorder.

The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18-29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults.

Pro-inflammatory cytokines and psychotherapy in depression: Results from a randomized clinical trial.

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.

Cocaine abuse and effects in the serum levels of cytokines IL-6 and IL-10.

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.

Stress, depression, quality of life and salivary cortisol levels in community health agents.

OBJECTIVE: To 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 Methods Cross-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. RESULTS: The 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. CONCLUSION: A 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.

The effect of proinflammatory cytokines in Cognitive Behavioral Therapy.

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 29years-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.

Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk.

Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD.