Association of sociocultural stressors with bipolar disorder onset in Puerto Rican youth growing up as members of a minoritized ethnic group: results from the Boricua Youth Longitudinal Study

BACKGROUND: The development of bipolar disorder is currently explained by a complex interaction of genetic and environmental factors. Less is known regarding the influence of sociocultural factors. This study aims to evaluate the incidence and impact of sociocultural factors on bipolar disorder onset in two comparable samples of youth growing up in different social settings. METHODS: We leveraged data from two urban population-based cohorts representative of Puerto Rican children growing up in either San Juan (Puerto Rico) or the South Bronx (NYC) and followed up for 17 years. Bipolar disorder diagnoses were based on retrospective self-reports on the World Health Organization Composite International Diagnostic Interview. We used a causal inference approach to estimate associations of sociocultural factors with bipolar disorder onset after adjusting for potential confounders. FINDINGS: We found that South Bronx children, who grew up as a minoritized group, had twice the risk of bipolar disorder onset as young adults, with an incidence rate of 2.22 new cases per 1000 person-years compared to 1.08 new cases in San Juan (incidence rate difference, 1.13; 95% CI, 0.09-1.20). After adjusting for potential confounders, South Bronx children had the same lifetime hazard of bipolar disorder onset compared to San Juan children. However, our analysis demonstrated that caregivers' exposure to societal cultural stress partially explained the increased risk of bipolar disorder onset in the South Bronx, in addition to the potential contribution of genetics. INTERPRETATION: Our results provide evidence that societal cultural stress can increase the risk of lifetime bipolar disorder onset in youth growing up as a minoritized group. Addressing stress in minoritized groups might reduce the risk of bipolar disorder onset. FUNDING: The Boricua Youth Study has been supported by the National Institutes of HealthMH56401, MH098374, DA033172, and AA020191. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article

Utilization of health services in relation to mental health problems in adolescents: A population based survey

BACKGROUND: Only a minority of adolescents reporting symptoms above case-levels on screenings for mental health seeks and receives help from specialist health services. The objective of this study was to a) examine help-seeking for symptoms of anxiety and depression in relation to symptom load dimensionally, b) identify the level of specialization in mental health among service-providers, and c) identify associations between mental health problems and contact with different types of health services. METHODS: This cross-sectional school-based study (response-rate 88%, n = 11154) is based on Norwegian health surveys among 15 and 16 year olds. RESULTS: We found a dose-response association between symptom-load and help seeking. Only 34% of individuals with mental symptom-load above 99(th )percentile reported help-seeking in the last 12 months. Forty percent of help seekers were in contact with specialists (psychiatrists or psychologists), the remaining were mainly in contact with GPs. Mental health problems increased help seeking to all twelve service providers examined. CONCLUSION: It might not be reasonable to argue that all adolescents with case-level mental health problems are in need of treatment. However, concerning the 99(th )percentile, claiming treatment need is less controversial. Even in the Norwegian context where mental health services are relatively available and free of charge, help-seeking in individuals with the highest symptom-loads is still low. Most help seekers achieved contact with health care providers, half of them at a non specialized level. Our results suggest that adolescents' recognition of mental health problems or intention to seek help for these are the major "filters" restricting treatment

Regularity of a kind of marginal functions in Hilbert spaces

We study well-posedness of some mathematical programming problem depending on a parameter that generalizes in a certain sense the metric projection onto a closed nonconvex set. We are interested in regularity of the set of minimizers as well as of the value function, which can be seen, on one hand, as the viscosity solution to a Hamilton-Jacobi equation, while, on the other, as the minimal time in some related optimal time control problem. The regularity includes both the Fréchet differentiability of the value function and the Hölder continuity of its (Fréchet) gradient

Exposure to the tsunami disaster, PTSD symptoms and increased substance use – an Internet based survey of male and female residents of Switzerland

BACKGROUND: After the tsunami disaster in the Indian Ocean basin an Internet based self-screening test was made available in order to facilitate contact with mental health services. Although primarily designed for surviving Swiss tourists as well as relatives and acquaintances of the victims, the screening instrument was open to anyone who felt psychologically affected by this disaster. The aim of this study was to evaluate the influences between self-declared increased substance use in the aftermath of the tsunami disaster, trauma exposure and current PTSD symptoms. METHODS: One section of the screening covered addiction related behavior. We analyzed the relationship between increased substance use, the level of PTSD symptoms and trauma exposure using multivariable logistic regression with substance use as the dependent variable. Included in the study were only subjects who reported being residents of Switzerland and the analyses were stratified by gender in order to control for possible socio-cultural or gender differences in the use of psychotropic substances. RESULTS: In women PTSD symptoms and degree of exposure enlarged the odds of increased alcohol, pharmaceuticals and cannabis use significantly. In men the relationship was more specific: PTSD symptoms and degree of exposure only enlarged the odds of increased pharmaceutical consumption significantly. Increases in alcohol, cannabis and tobacco use were only significantly associated with the degree of PTSD symptoms. CONCLUSION: The tsunami was associated with increased substance use. This study not only replicates earlier findings but also suggests for a gender specificity of post-traumatic substance use increase

Localization of Human RNase Z Isoforms: Dual Nuclear/Mitochondrial Targeting of the ELAC2 Gene Product by Alternative Translation Initiation

RNase Z is an endonuclease responsible for the removal of 3′ extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase ZL) encoded by ELAC2, and a short form (RNase ZS; ELAC1). We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase ZS was found in the cytosol, whereas RNase ZL localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase ZL. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase ZL is the enzyme involved in both, nuclear and mitochondrial tRNA 3′ end maturation

A survey of green plant tRNA 3'-end processing enzyme tRNase Zs, homologs of the candidate prostate cancer susceptibility protein ELAC2

<p>Abstract</p> <p>Background</p> <p>tRNase Z removes the 3'-trailer sequences from precursor tRNAs, which is an essential step preceding the addition of the CCA sequence. tRNase Z exists in the short (tRNase Z^S) and long (tRNase Z^L) forms. Based on the sequence characteristics, they can be divided into two major types: bacterial-type tRNase Z^Sand eukaryotic-type tRNase Z^L, and one minor type, <it>Thermotoga maritima </it>(TM)-type tRNase Z^S. The number of tRNase Zs is highly variable, with the largest number being identified experimentally in the flowering plant <it>Arabidopsis thaliana</it>. It is unknown whether multiple tRNase Zs found in <it>A. thaliana </it>is common to the plant kingdom. Also unknown is the extent of sequence and structural conservation among tRNase Zs from the plant kingdom.</p> <p>Results</p> <p>We report the identification and analysis of candidate tRNase Zs in 27 fully sequenced genomes of green plants, the great majority of which are flowering plants. It appears that green plants contain multiple distinct tRNase Zs predicted to reside in different subcellular compartments. Furthermore, while the bacterial-type tRNase Z^Ss are present only in basal land plants and green algae, the TM-type tRNase Z^Ss are widespread in green plants. The protein sequences of the TM-type tRNase Z^Ss identified in green plants are similar to those of the bacterial-type tRNase Z^Ss but have distinct features, including the TM-type flexible arm, the variant catalytic HEAT and HST motifs, and a lack of the PxKxRN motif involved in CCA anti-determination (inhibition of tRNase Z activity by CCA), which prevents tRNase Z cleavage of mature tRNAs. Examination of flowering plant chloroplast tRNA genes reveals that many of these genes encode partial CCA sequences. Based on our results and previous studies, we predict that the plant TM-type tRNase Z^Ss may not recognize the CCA sequence as an anti-determinant.</p> <p>Conclusions</p> <p>Our findings substantially expand the current repertoire of the TM-type tRNase Z^Ss and hint at the possibility that these proteins may have been selected for their ability to process chloroplast pre-tRNAs with whole or partial CCA sequences. Our results also support the coevolution of tRNase Zs and tRNA 3'-trailer sequences in plants.</p

A connectome of the adult drosophila central brain

The neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions. Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain

A connectome and analysis of the adult Drosophila central brain

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain

Humanities for the Future: a new European Agenda

FGW – Publications not associated with a particular research are