The role of metabolic syndrome as a mediator in the relationship between CCL11 levels and the presence of a mood episode with mixed features in young adults with bipolar disorder.

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.

Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in S. albidoflavus.

Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.

Exploring protective factors in a high-risk subsample: the pivotal role of paternal support in preventing depression in a cohort of young adults.

BACKGROUND: Major depressive disorder (MDD) is a global concern due to its widespread prevalence and morbidity. Identifying protective factors in high-risk individuals, including those with a familial predisposition, maltreatment history, and socio-economic vulnerabilities, is crucial. METHODS: We assessed a high-risk subsample within a young adult population cohort (n = 791; mean age = 31.94 [SD = 2.18]) across three waves. Using multiple regression models to analyse higher education, feeling supported, spirituality, psychotherapy access, higher socioeconomic status, involvement in activities, cohabitation, and family unity in Waves 1 and 2, and their association with MDD resilience at Wave 3. RESULTS: In the high-risk group, MDD incidence was 13.7% (n=24). Paternal support had a protective effect on MDD incidence (OR = 0.366; 95% CI [0.137 to 0.955], p = 0.040) and suicidal attempt risk (OR = 0.380; 95% CI [0.150 to 0.956], p = 0.038). Higher resilience scores were also protective (OR = 0.975; 95% CI [0.953 to 0.997], p = 0.030), correlating with reduced BDI (r = 0.0484; B = -0.2202; 95% CI [-0.3572 to -0.0738]; p = 0.003) and MADRS scores (r = 0.0485; B = -0.2204; 95% CI [-0.3574 to -0.0741]; p = 0.003). CONCLUSIONS: Our paper emphasizes reorienting the MDD approach, focusing on positive prevention strategies. It highlights fathers' crucial role in family-based interventions and promoting resilience in high-risk populations.

Pepticinnamins N, O, and P, Nonribosomal Peptides from the Soil-Derived Streptomyces mirabilis P8-A2.

Cinnamoyl moiety containing nonribosomal peptides represented by pepticinnamin E are a growing family of natural products isolated from different Streptomyces species and possess diverse bioactivities. The soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E (1) and its analogues, pepticinnamins N, O, and P (2-4), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey's reactions. These new compounds did not show a growth inhibitory effect against the LNCaP and C4-2B prostate cancer lines, respectively.

Whitehead, Tansley, Sen, Bobbio e a abordagem One Health / Whitehead, Tansley, Sen, Bobbio and the One Health approach / Whitehead, Tansley, Sen, Bobbio y el enfoque One Health

Objetivo: traçar parâmetros para estruturar conceitos da abordagem One Health através dos pensamentos de Alfred North Whitehead, Arthur George Tansley, Amartya Sen e Norberto Bobbio. Metodologia: tratou-se de pesquisa original, com abordagem dedutiva e viés hermenêutico, baseada nos pensamentos selecionados e na orientação de Saúde Única. Resultados: One Health estrutura-se na afirmativa holística e integrada que a saúde humana, animal e ambiental estão interligadas. Sob a perspectiva de Whitehead, a abordagem One Health pode ser considerada um processo dinâmico e relacional, onde humanos, animais e meio ambiente interagem constantemente, interconectando-se por relações e processos, formando um todo. Pela perspectiva de Tansley, a ideia de One Health pode alinhar-se ao conceito de ecossistema, não podendo a saúde ser analisada isoladamente em indivíduos, mas, necessariamente, pelas interações complexas entre seres humanos, animais e o ambiente. Sob o prisma de desenvolvimento (direitos e liberdades), proposto por Sen, a abordagem One Health pode ser considerada um meio para alcançá-lo, através da interrelação de mecanismos, sistemas e instituições focados na promoção da saúde e do bem-estar. Na visão de Bobbio, direitos fundamentais, democracia e a paz, são formas éticas e primordiais para assegurar direitos, especialmente um novo direito da natureza (humanos, animal e ambiente) na busca conjunta de garantias para a convivência pacífica. Conclusão: a abordagem One Health não é apenas uma estratégia prática, mas também uma visão renovada da antiga percepção que reconhecia a interconexão de todas as formas de vida.

Objective: draw parameters to structure concepts of the One Health approach through the thoughts of Alfred North Whitehead, Arthur George Tansley, Amartya Sen, and Norberto Bobbio. Methodology: this was original research, with a deductive approach, hermeneutic bias based on the selected thoughts and the One Health. Results: One Health is structured on the holistic and integrated assertion that human, animal, and environmental health are interconnected. From Whitehead's perspective, the One Health approach can be considered a dynamic and relational process, where humans, animals, and the environment constantly interact, interconnecting through relationships and processes, forming a whole. From Tansley's perspective, the idea of One Health can align with the ecosystem concept, where health cannot be analyzed in isolation in individuals, but necessarily through the complex interactions between humans, animals, and the environment. From Sen's development prism (rights and freedoms), the One Health approach can be seen to achieve it, through the interrelation of mechanisms, systems, and institutions focused on promoting health and well-being. In Bobbio's view, fundamental rights, democracy, and peace are ethical and primary ways to ensure rights, especially a right of nature (humans, animals, and the environment) in the joint pursuit of guarantees for peaceful coexistence. Conclusion: the One Health approach is not just a practical strategy, but also a renewed vision of the old perception that recognized the interconnection of all forms of life.

Objetivo: establecer parámetros para estructurar conceptos del enfoque One Health a través de los pensamientos de Alfred North Whitehead, Arthur George Tansley, Amartya Sen y Norberto Bobbio. Metodología: se trató de una investigación original, con un enfoque deductivo, sesgo hermenéutico basado en los pensamientos seleccionados y el Salud Única. Resultados: One Health se estructura en la afirmación holística e integrada de que la salud humana, animal y ambiental están interconectadas. Desde la perspectiva de Whitehead, el enfoque One Health puede considerarse un proceso dinámico y relacional, donde humanos, animales y el medio ambiente interactúan constantemente, interconectándose a través de relaciones y procesos, formando un todo. Desde la perspectiva de Tansley, la idea de One Health puede alinearse con el concepto de ecosistema, donde la salud no puede analizarse aisladamente en individuos, sino necesariamente a través de interacciones complejas entre seres humanos, animales y el ambiente. Desde el prisma del desarrollo (derechos y libertades) propuesto por Sen, el enfoque One Health puede considerarse un medio para alcanzarlo, a través de la interrelación de mecanismos, sistemas e instituciones enfocados en la promoción de la salud y el bienestar. Desde la visión de Bobbio, los derechos fundamentales, la democracia y la paz son formas éticas y primordiales para asegurar derechos, especialmente un derecho de la naturaleza (humanos, animales y ambiente) en la búsqueda conjunta de garantías para la convivencia pacífica. Conclusión: el enfoque One Health no es solo una estrategia práctica, sino también una visión renovada de la antigua percepción que reconocía la interconexión de todas las formas de vida.

Factors associated with suicide risk in young women with premenstrual dysphoric disorder: A population-based study.

PURPOSE: Women with premenstrual dysphoric disorder (PMDD) are more likely to report suicide ideation and behavior when compared to women without PMDD. However, there is a lack of studies investigating the risk factors for suicide risk in women with PMDD. Thus, the aim of this study is to assess the factors associated with suicide risk in young women with PMDD. METHODS: This is a cross-sectional study including 128 young women with PMDD who were recruited from the community. PMDD and suicide risk were assessed by trained psychologists using the Mini International Neuropsychiatric Interview (MINI-PLUS). Suicide risk evaluation includes six questions that assess suicidal intention, planning and previous attempts. Subjects who answer yes to any of the six questions are classified as having current suicide risk. RESULTS: The prevalence of current suicide risk in women with PMDD was 28.1%. The factors associated with suicide risk in this population were: presenting current panic disorder (OR: 18.71 [95% CI: 1.02 - 343.27], p=0.048), a non-white skin color (OR: 4.18 [CI 95%: 1.28 - 13.61], p=0.018), greater severity of depressive symptoms (OR: 1.22 [95% CI: 1.12 - 1.32], < 0.001), and history of childhood trauma (OR: 1.04 [95% CI: 1.01 - 1.08], 0.010). CONCLUSION: Our findings indicate that there are key sociodemographic and clinical factors associated with suicide risk in young women with PMDD, enabling clinicians to identify at-risk individuals who could benefit from further screening and interventions.

Are big five personality traits associated to suicidal behaviour in adolescents? A systematic review and meta-analysis.

BACKGROUND: Suicidal behaviour is one of the main causes of death worldwide, especially among teenagers, and its development is potentially associated with the development of personality. The aim of this systematic review and meta-analysis is to describe the association between the Big Five Personality Traits and suicidal behaviour in adolescents. METHODS: Seven databases were systematically searched between June 2022 and July 2022 with no language or year restrictions. We searched for a combination of the following search items (suicid* OR suicidal behaviour OR suicidal ideation OR suicide attempts OR self injury OR self-destructive behaviour OR self-harm OR suicidal risk) AND (personality OR personality traits OR temperament OR neuroticism OR extraversion OR agreeableness OR openness to experience OR conscientiousness) AND (adolescents OR youth OR teenagers OR young adults). Meta-analysis procedures were performed using the R software. A random-effect-model was performed for the models through the incorporation of τ2, based on the DerSimonion Lard method. RESULTS: Seven studies met all inclusion criteria and were included in this systematic review. Our meta-analysis showed that higher neuroticism are both associated and a risk factor for suicidal behaviour. Higher levels of openness to experience and agreeableness, and lower levels of extraversion and conscientiousness, were linked to suicidal behaviour, especially self-harm. LIMITATIONS: Due to the heterogeneity of the studies, we were only able to perform meta-analysis regarding neuroticism. CONCLUSION: The present study may help professionals to identify adolescents in higher risk for suicidal behaviour, enabling the development of early interventions to prevent suicidality in this population.

Cross-cultural adaptation and psychometric properties of the Iowa-Netherlands Comparison Orientation Measure for the Brazilian context

Abstract Introduction The Iowa-Netherlands Comparison Orientation Measure (INCOM) was developed to measure individual differences in social comparison orientation and has been widely used in research and various different settings. Objectives The aim of this study was to adapt the online version of the INCOM and to evaluate its psychometric parameters when applied to a Brazilian population of university students. Methods The procedures were divided into two steps: step 1 - cross-cultural adaptation and analysis of content validity, and step 2 - assessment of psychometric characteristics. Step 1 comprised the processes of translation, evaluation by an expert committee, evaluation by the target population, and back-translation. For step 2, 1,065 university students were recruited and then factor analysis, analysis of reliability, and analysis of validity based on external measures were performed. Results The adaptation process yielded satisfactory results, including good indicators of content validity. Exploratory factor analysis revealed a two-dimensional structure and adequate factor loadings, except for item 11, which was excluded from the final version. Additionally, the final version of the scale had adequate fit indices (χ2 = 148.45, degrees of freedom [df] = 26; p < 0.001; root mean square error of approximation [RMSEA] = 0.06; comparative fit index [CFI] = 0.99; and Tucker-Lewis index [TLI] = 0.98). Evidence of reliability (Cronbach's alpha = 0.83) was observed and there were positive correlations with negative affect (r = 0.36) and negative correlations with positive affect and self-esteem (r = -0.15; r = -0.41, respectively). Conclusion The Brazilian version of the INCOM presents satisfactory psychometric parameters and can thus be used to measure social comparison orientation.

Chromosomal organization of multigene families and meiotic analysis in species of Loricariidae (Siluriformes) from Brazilian Amazon, with description of a new cytotype for genus Spatuloricaria.

In the Amazon, some species of Loricariidae are at risk of extinction due to habitat loss and overexploitation by the ornamental fish market. Cytogenetic data related to the karyotype and meiotic cycle can contribute to understanding the reproductive biology and help management and conservation programs of these fish. Additionally, chromosomal mapping of repetitive DNA in Loricariidae may aid comparative genomic studies in this family. However, cytogenetics analysis is limited in Amazonian locariids. In this study, chromosomal mapping of multigenic families was performed in Scobinancistrus aureatus, Scobinancistrus pariolispos and Spatuloricaria sp. Meiotic analyzes were performed in Hypancistrus zebra and Hypancistrus sp. "pão". Results showed new karyotype for Spatuloricaria sp. (2n=66, NF=82, 50m-10sm-6m). Distinct patterns of chromosomal organization of histone H1, histone H3 and snDNA U2 genes were registered in the karyotypes of the studied species, proving to be an excellent cytotaxonomic tool. Hypotheses to explain the evolutionary dynamics of these sequences in studied Loricariidae were proposed. Regarding H. zebra and H. sp. "pão", we describe the events related to synapse and transcriptional activity during the meiotic cycle, which in both species showed 26 fully synapsed bivalents, with high gene expression only during zygotene and pachytene. Both Hypancistrus species could be used may be models for evaluating changes in spermatogenesis of Loricariidae.

Predicting functional impairment in euthymic patients with mood disorder: A 5-year follow-up.

Major Depressive Disorder and Bipolar Disorder are psychiatric disorders associated with psychosocial impairment. Despite clinical improvement, functional complaints usually remain, mainly impairing occupational and cognitive performance. The aim of this study was to use machine learning techniques to predict functional impairment in patients with mood disorders. For that, analyzes were performed using a population-based cohort study. Participants diagnosed with a mood disorder at baseline and reassessed were considered (n = 282). Random forest (RF) with previous recursive feature selection and LASSO algorithms were applied to a training set with imputed data by bagged trees resulting in two main models. Following recursive feature selection, 25 variables were retained. The RF model had the best performance compared to LASSO. The most important variables in predicting functional impairment were sexual abuse, severity of depressive, anxiety, and somatic symptoms, physical neglect, emotional abuse, and physical abuse. The model demonstrated acceptable performance to predict functional impairment. However, our sample is composed of young participants and the model may not generalize to older individuals with mood disorders. More studies are needed in this direction. The presented calculator has clinical, sociodemographic, and environmental data, demonstrating that it is possible to use such information to predict functional performance.

Ego-defense mechanisms and brief psychotherapies for the management of major depressive disorder in adults: A longitudinal and quasi-experimental study.

OBJECTIVE: To evaluate the effect of psychotherapies on ego defense mechanisms and the reduction of depressive symptoms in a 12-month follow-up period. METHODS: This longitudinal and quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18-60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. Two models of psychotherapy were used: Supportive Expressive Dynamic Psychotherapy (SEDP) and Cognitive Behavioral Therapy (CBT). Defense Style Questionnaire 40 was used to analyze defense mechanisms and the Beck Depression Inventory was used to measure the depressive symptoms. RESULTS: The total sample comprised 195 patients (113 SEDP and 82 CBT), with the mean age was 35.63 (11.44) years. After adjustments, increased mature defenses was significantly associated with reduced depressive symptoms at all follow-up times (p < 0.001) and the decrease in immature defenses was significantly associated with the reduction of depressive symptoms at all follow-up times (p < 0.001). While neurotic defenses were not associated with a reduction in depressive symptoms at any time of follow-up (p > 0.05). CONCLUSION: Both models of psychotherapy were effective in increasing mature defenses and decreasing immature ones, as well as decreasing depressive symptoms at all evaluation times. With this, it is understood that a greater understanding of these interactions will allow a more adequate diagnostic and prognostic evaluation and the design of useful strategies that adapt to the patient's reality.

Biological rhythms disruption mediates the association between mother's diagnosis of bipolar disorder and offspring's emotional/behavioral problems.

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.

Childhood trauma, inflammatory biomarkers and the presence of a current depressive episode: Is there a relationship in subjects from a population study?

This study aims to compare the serum cytokine levels between controls, individuals with a current depressive episode (CDE) with childhood trauma and individuals with CDE without childhood trauma. This is a cross-sectional with paired sample nested in a population-based study. For the purposes of the current study, subjects who had psychotic symptoms, generalized anxiety disorder, and who refused to perform blood collection were excluded. Subsequently, only individuals who had a current depressive episode were selected (n = 76). Another 76 subjects were randomly paired by sex and age, constituting a population control group. The measurements of serum cytokine levels were performed using the multiplex analysis method. In the group with a CDE, when compared to the population control group, the following cytokines were high: IL-1ß, IL-2, IL-4, IL-6, IL-17A, IFN-γ and TNF-α (p < 0.05). On the other hand, there was a decrease in the levels of cytokines IL-10 (p = 0.027) and IL12p70 (p = 0.001). Bonferroni test demonstrates that there is no statistically significant difference in serum cytokine levels between subjects with a CDE, with and without trauma (p > 0.05). In a multivariable logistic regression, adjusting for socioeconomic status, tobacco, alcohol and illicit drugs abuse/dependence, and use of psychiatric medication, we found that cytokines serum levels remained associated with CDE even when adjusted for these potential confounders. Our findings demonstrate that monitoring cytokine levels and immune function may be beneficial in preventing the development of a CDE. However, future research is necessary to investigate the impact of trauma on the relationship between inflammation and CDE.

Maternal expression of miR-let-7d-3p and miR-451a during gestation influences the neuropsychomotor development of 90 days old babies: "Pregnancy care, healthy baby" study.

INTRODUCTION: Studies on maternal microRNA expression have emerged to better understand regulatory mechanisms during the gestational period, since microRNA expression has been associated with pregnancy disorders. OBJECTIVES: This study aims to investigate the association between the expression of the maternal microRNAs miR-let-7d-3p and miR-451a during the second gestational trimester and neuropsychomotor development at 90 days of life of infants. METHODS: This is a case-control study nested within a cohort, with the groups being divided into dyads in which pregnant women presented Major Depressive Episode (MDE) (n = 64), these being the cases, and their respective controls (no MDE; n = 64). The Bayley Scale III was used to assess the outcome of child development, and MDE was assessed through the Mini International Neuropsychiatric Interview Plus. The analysis of miR-let-7d-3p and miR-451a was done via serum from the pregnant women, utilizing the qRT-PCR (n = 128). RESULTS: The results indicated a negative association between expression levels of miR-451a (ß -3.3 CI95% -6.4;-0.3) and a positive associated of the miR-let-7d-3p with the cognitive development domain (ß 1.7 CI95% 0.1; 3.0), and a positive association between expression of miR-let-7d-3p with motor development of the infants (ß 1.6 CI95% 0.3; 2.9). CONCLUSION: This is a pioneering study on the topic that indicates a biological interrelationship between the miRNAs miR-let-7d-3p and miR-451a evaluated during the pregnancy and the motor and cognitive domains of infant development at 90 days postpartum.

Cross-cultural adaptation and psychometric properties of the Iowa-Netherlands Comparison Orientation Measure for the Brazilian context.

INTRODUCTION: The Iowa-Netherlands Comparison Orientation Measure (INCOM) was developed to measure individual differences in social comparison orientation and has been widely used in research and different contexts. The aim of this study was to adapt the online version of the INCOM and to evaluate its psychometric parameters when applied to a Brazilian population of university students. METHODS: The procedures were divided into two steps: step 1 - cross-cultural adaptation and content validity, and step 2 - assessment of psychometric characteristics. In step 1, the processes of translation, evaluation by expert committee, evaluation by the target population, and the back-translation, were performed. In step 2, 1065 university students participated and factor analysis, analysis of reliability and validity based on external measures were performed. RESULTS: The adaptation process showed satisfactory results, such as good indicators of content validity. Exploratory factor analysis indicated a two-dimensional structure and adequate factor loadings, except for item 11, which was excluded from the final version. Also, the final version of the scale presented adequate fit indices (χ2 = 148.45, df = 26; p < 0.001; RMSEA = 0.06; CFI = 0.99; TLI = 0.98). Evidence of reliability (Cronbach's alpha = 0.83) was found, in addition to positive correlations with negative affect (r =0.36) and negative correlations with positive affect and self-esteem (r = -0.15; r = -0.41, respectively). CONCLUSION: The Brazilian version of the INCOM presents satisfactory psychometric parameters and can thus be used to measure social comparison orientation.

Theoretical procedures of the cross-cultural adaptation process of the Child Mania Rating Scale - Parent Version (CMRS-P) for the Brazilian context.

OBJECTIVES: To describe the theoretical procedures employed in the process of cross-cultural adaptation (CCA) for Brazil of the Child Mania Rating Scale - Parent Version (CMRS-P). METHODS: Seven steps were carried out: (1) translations and synthesis; (2) Committee of Judges-I; (3) grammatical review; (4) Committee of Judges-II; (5) semantic analysis (pre-test); (6) back-translation; and (7) discussion with the authors of the original instrument. Participants were two professional translators, 14 experts, a grammar proofreader, and 21 parents/guardians, representatives of the target population. The results were analyzed in terms of the percentage of agreement between evaluators and the content validity coefficient (CVC) and by analysis of comments and suggestions. RESULTS: Grammatical and cultural adjustments were made, in addition to substitution and/or inclusion of words and examples. Adequacy agreement indexes exceeding 86% were achieved and the CVC result for the total scale was excellent (0.95). The pre-test indicated good acceptance and understanding by participants. CONCLUSION: The proposed version proved to be promising for use in the Brazilian context, although further psychometric studies are still needed to prove the scale's validity and reliability.

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.

Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women.

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.