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Mixed features presentation in bipolar disorder (BD) represents the most severe form of the disease. BD may lead to cognitive and functional deterioration, a process known as neuroprogression, which appears to be exacerbated by increased serum levels of CCL11, a neuroprogression-related cytokine. Metabolic syndrome (MetS) is highly prevalent in BD, and it is known that the presence of MetS may increase inflammation, which may contribute to increased CCL11 levels, and consequently impact on the severity of the disorder. What is not known is whether the MetS mediates the association between CCL11 levels and the presence of mood episodes with mixed features in BD. Therefore, the aim of this study was to investigate the mediating effect of MetS on the relationship between CCL11 levels and the presence of mood episodes with mixed features in BD, in a population-based study. This is a cross-sectional study that included 184 young adults, 92 with BD and 92 populational controls, matched by sex and age. BD diagnosis was assessed using the Mini International Neuropsychiatric Interview - PLUS. Mood episodes with mixed features was defined according to DSM-IV and DSM-5 criteria. MetS was defined according to the National Cholesterol Education Program (NCEP/ATP III). Substance use was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). CCL11 serum levels were analyzed using the multiplex analysis method Luminex 200™ system. The mediation model was tested using the MedMod module of the JAMOVI 2.4.8 software. Mediation analysis indicated a trend towards significance of MetS mediating the association between CCL11 and the presence of a mood episode with mixed features in BD (p = 0.065). Individuals with BD presenting with a mood episode with mixed features and MetS may have accelerated neuroprogression due to the influence of MetS on CCL11 levels, therefore, assessing for MetS occurrence in this population and implementing early interventions to prevent its development may be effective ways of delaying cognitive impairments related to this cytokine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The current study assesses whether the association between diagnosis of Bipolar Disorder (BD) in mothers and emotional and behavioral problems (EBP) in their offspring is mediated by a disruption in the offspring's biological rhythms., Methods: A probabilistic sample of 492 public school children (ages 7-8, 48 % female) were assessed for biological rhythms disruption and EBP using the Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids and the Strengths and Difficulties Questionnaire, respectively. Mothers' mental health (BD = 64) was evaluated using a standardized clinical interview. A mediation analysis was conducted to assess the effect of the mother's diagnosis of BD on the EBP of their offspring in relation to the offspring's biological rhythms disruptions., Results: When compared to offspring of mothers without BD, offspring of mothers with BD showed greater difficulty in maintaining biological rhythms and higher prevalence of EBP. Using the presence of EBP as the outcome, 75 % of the effect of mother's BD diagnosis was mediated by offspring's biological rhythms disruption., Conclusions: Biological rhythms disruption in children fully mediates the effect of the mother's diagnosis of BD on the child's EBP. These data encourage the development of further studies to find effective strategies to prevent and treat biological rhythms disruption in offspring of mothers with BD., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18-35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737-rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: 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)., Method: 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., Results: 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) p<0.001. 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., Conclusion: 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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is a neuropsychiatric disorder characterized by recurrent episodes of mania/hypomania, affecting more than 1% of the world population. S100B is a calcium-binding protein, mostly produced and secreted by astrocytes in the CNS that participate in several cellular responses. Previous studies have shown that patients with bipolar disorder had higher peripheral S100B levels than healthy individuals, suggesting a potential role for S100B BD., Methods: In this study, a systematic and quantitative meta-analysis of studies S100B serum was performed according to the guidelines PRISMA-statement to confirm the increase of serum S100B in patients with manic bipolar disorder., Results: We included in the meta-analysis two studies that reported the mean and standard deviation of serum S100B 52 patients manic BP and 52 control studies. Our results showed higher levels of S100B peripheral TB patients compared with healthy controls. In this meta-analysis, we found evidence that serum S100B are increased in patients with bipolar disorder., Conclusion: In conclusion, several studies have observed morphological abnormalities in the brains of bipolar disorder patients, changes in the peripheral S100B levels in mood disorders were described, and this protein could be a putative marker for damage to the brain. Thus, in this meta-analysis we have found evidence, based on two studies of 52 patients and 52 healthy controls, that the serum concentrations of S100B are increased in bipolar disorder patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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.

Objective: We describe the prevalence of depressive and bipolar spectrum episodes in fathers in antenatal and postnatal periods, as well as at 12 months after childbirth., Method: A longitudinal follow-up study was conducted with a representative sample of 739 fathers whose children were born between April 2007 and May 2008 in maternity wards in the city of Pelotas, southern Brazil. Paternal psychopathology was measured with the Mini Neuropsychiatric Interview (MINI) across three time points: between 28 and 34 weeks of pregnancy (T1), 30 to 60 days postpartum (T2), and 12 months after childbirth (T3)., Results: The prevalence of depressive episodes was 5.0% at T1, 4.5% at T2, and 4.3% at T3. Mixed episodes were present in 3%, 1.7%, and 0.9% of subjects, respectively, and accounted for 61.1% of the cases of depression in the antenatal period, 37.5% in postpartum, and 21.4% at 12 months. Depressive and manic/hypomanic episodes were significantly associated during pregnancy and in postpartum, but not at 12 months after childbirth., Conclusion: Bipolar episodes were common in men with depressive symptoms during their partner's pregnancy in the postpartum period and, to a lesser extent, 12 months after childbirth. Therefore, this population should be carefully investigated for manic and hypomanic symptoms.

Objective: To identify the association of metabolic syndrome (MetS) and psychiatric disorders in young adults in southern Brazil. Methods: This population based cross-sectional study involved a total of 1,023 young adults between the ages of 21 and 32 years. Current episodes of psychiatric disorders were assessed using the Mini International Neuropsychiatric Interview - Plus version. MetS was evaluated using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). Results: Of the 1,023 participants, 24.3% were identified with MetS, 13.5% were diagnosed with anxiety disorders, 7.5% with current depression, 3.9% with bipolar disorders and 10.1% were at risk of suicide. MetS was associated with ethnicity (p = 0.022), excess weight (p < 0.001), current anxiety disorders (p < 0.001), current mood disorders (bipolar disorder in mood episode and current depression) (p < 0.001), and suicide risk (p < 0.001). Conclusions: MetS was associated with psychiatric disorders. Awareness of factors associated with MetS can help identify high-risk individuals and stimulate disease prevention and control programs, as well as lifestyle changes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]