A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders.

Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.

Neural correlates of negative and disease-specific emotional stimuli in panic disorder: a functional magnetic resonance imaging study.

OBJECTIVE: Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gyrus, of both panic-related and negative conditions among individuals with PD and healthy controls. METHODS: We examined 13 medication-free PD patients and 14 healthy controls with functional magnetic resonance imaging (fMRI) during exposure to negative and neutral pictures and a set of specific panic-related pictures. RESULTS: Subtraction between the conditions indicated activation of the left amygdala region and the right inferior frontal gyrus in PD patients during the specific panic-related condition, whereas the left amygdalar region and left inferior frontal gyrus were activated during the negative condition in controls. CONCLUSION: These results suggest that in patients with PD, a prominent bottom-up process is involved in specific panic-related conditions, which might be associated with weak modulation of the left frontal area. These data add to our current understanding of the neural correlates of PD and can contribute to future clinical interventions targeting the functional reestablishment of these regions.

Neonatal screening tests in Brazil: prevalence rates and regional and socioeconomic inequalities / Realização dos testes de triagem neonatal no Brasil: prevalências e desigualdades regionais e socioeconômicas

Abstract Objective: To identify the prevalence and associated factors with the performance of the Guthrie test, hearing, and red reflex screening tests in Brazil. Methods: This was a population-based, cross-sectional study that analyzed data on 5,231 children under 2 years of age participating in the National Health Survey of 2013. The study described the prevalence and Confidence Intervals (95% CI) of the three neonatal screening tests performed, in any period, and their association with the country's regions, skin color/ethnicity, private health insurance, and per capita household income. Logistic regression models were used, and odds ratios were calculated by incorporating sample weights. Results: The prevalence of Guthrie test screening in Brazil at any time of life was 96.5%, that of the newborn hearing screening was 65.8% and that of the red reflex screening test was 60.4%. The performance of the three screening tests was significantly higher among children whose mothers/guardians reported higher per capita household income, who lived in the South and Southeast regions, and who had private health insurance (p < 0.001). There was no statistically significant difference regarding the performance of the tests according to skin color/ethnicity (p > 0.05). The same inequalities were verified when the tests were performed during the recommended periods, with a strong socioeconomic gradient. Conclusions: There are inequalities in the performance of neonatal screening tests in the country, and also in the performance of these tests during the periods established in the governmental guidelines. The guarantee of the performance of these tests in a universal and public health system, as in Brazil, should promote equity and access to the entire population.

Resumo Objetivo: Identificar prevalência e fatores associados à realização dos testes do pezinho, da orelhinha e do olhinho no Brasil. Método: Estudo transversal analítico de base populacional que analisou os dados de 5.231 crianças menores de dois anos participantes da Pesquisa Nacional de Saúde (2013). Foram descritas prevalências e intervalos de confiança (95% IC) da realização dos três testes de triagem neonatal, em qualquer período, e sua associação com as regiões do país, cor/etnia, posse de plano de saúde e renda domiciliar per capita. Empregaram-se modelos de regressão logística e calcularam-se as odds ratio e incorporaram-se os pesos amostrais. Resultados: A prevalência de realização do teste do pezinho no Brasil em qualquer momento de vida foi de 96,5%; do teste da orelhinha de 65,8% e do teste do olhinho de 60,4%. A realização dos três testes de triagem foi significativamente maior entre as crianças cujas mães/responsáveis reportaram maior renda domiciliar per capita, residiam nas regiões Sul e Sudeste e tinham plano de saúde (p < 0,001). Não houve diferença estatisticamente significativa na realização dos testes segundo cor/etnia (p > 0,05). As mesmas desigualdades foram verificadas para a realização dos testes no período preconizado, com forte gradiente socioeconômica. Conclusões: Existem desigualdades na realização dos testes de triagem neonatal no país e, também, na realização desses dentro dos prazos previstos nas diretrizes governamentais. A garantia desses testes em um sistema universal e público como no Brasil deveria promover a equidade e o acesso a toda a população.

Depression and Health Self-perception: Associations Within the Isolated Mennonite Population in South Brazil.

The Mennonite population suffered several bottlenecks due to religious/political persecution, increasing the frequency of diseases with a strong genetic component. We evaluated health self-perception in 430 Mennonites from South Brazilian settlements (two rural, one urban), along with life habits, xenobiotic exposure, and chronic ilnesses, using a modified version of the 2013 Brazilian National Health Survey and eight psychometric tests (applied in 2016-2018). Mennonites from rural settlements considered their health worse (P < 0.0001). This was independently associated with any psychiatric disease (OR 3.10, P = 0.037), depression diagnosis (OR 2.39, P = 0.002), spinal pain (OR 1.76, P = 0.015), waist circumference (OR 1.02, P = 0.009) and geographic origin (OR 0.64, P = 0.003). In the multivariate analysis including the scales, independent association also occurred with higher anxiety (ASI-R: OR 6.48, P = 0.014) and depression scores (BDI: OR 6.72, P = 0.008). Thus, a worse health self-perception was unequivocally associated with diagnosed or present depression/anxiety, independent of other contributors, suggesting a strong link between both.

Neonatal screening tests in Brazil: prevalence rates and regional and socioeconomic inequalities.

OBJECTIVE: To identify the prevalence and associated factors with the performance of the Guthrie test, hearing, and red reflex screening tests in Brazil. METHODS: This was a population-based, cross-sectional study that analyzed data on 5,231 children under 2 years of age participating in the National Health Survey of 2013. The study described the prevalence and Confidence Intervals (95% CI) of the three neonatal screening tests performed, in any period, and their association with the country's regions, skin color/ethnicity, private health insurance, and per capita household income. Logistic regression models were used, and odds ratios were calculated by incorporating sample weights. RESULTS: The prevalence of Guthrie test screening in Brazil at any time of life was 96.5%, that of the newborn hearing screening was 65.8% and that of the red reflex screening test was 60.4%. The performance of the three screening tests was significantly higher among children whose mothers/guardians reported higher per capita household income, who lived in the South and Southeast regions, and who had private health insurance (p<0.001). There was no statistically significant difference regarding the performance of the tests according to skin color/ethnicity (p>0.05). The same inequalities were verified when the tests were performed during the recommended periods, with a strong socioeconomic gradient. CONCLUSIONS: There are inequalities in the performance of neonatal screening tests in the country, and also in the performance of these tests during the periods established in the governmental guidelines. The guarantee of the performance of these tests in a universal and public health system, as in Brazil, should promote equity and access to the entire population.