Finding Rare, Disease-Associated Variants in Isolated Groups: Potential Advantages of Mennonite Populations

Large-scale genotyping and next-generation sequencing techniques have allowed great advances in the field of molecular genetics. Numerous common variants of low impact have been associated with many complex human traits and diseases, such as bipolar disorder and schizophrenia. Although they may exert a greater impact on risk, few rare disease variants have been found, owing to the greatly increased sample sizes that are typically necessary to demonstrate association with rarer variants. One alternative strategy is to study isolated populations, where historical bottlenecks reduce genetic diversity and some otherwise rare variants may drift to higher frequencies. Here we describe the Mennonite population settlements, considering their history of multiple bottlenecks followed by demographic expansion and a currently widespread geographical distribution. We argue that Mennonite populations are valuable partners for studies seeking genetic variants that exert a high impact on risk for a variety of common disorders, including mental illnesses

Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study

BACKGROUND: Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice. METHODS: A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18–40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients. RESULTS: At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others. CONCLUSIONS: Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide information on the most relevant items to be considered when conducting cost-effectiveness studies comparing specific alternatives for the treatment of target patients

Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: Results from the COMETA study

Background: Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice.Methods: A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18-40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients.Results: At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others.Conclusions: Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide information on the most relevant items to be considered when conducting cost-effectiveness studies comparing specific alternatives for the treatment of target patients

Tradução e adaptação transcultural do Questionário de Atividade Física Habitual

BACKGROUND: There has been a growing scientific interest on the interface between exercise and psychiatric disorders. However, there is a lack of self-report instruments to assess levels of physical activity adapted to Brazilian Portuguese. OBJECTIVE: To translate, assess the semantic equivalence of the Habitual Physical Activity Questionnaire and perform a non-psychometric pre-test with subjects (n = 30) from the Brazilian population, with different educational backgrounds. METHODS: The cross-cultural adaptation process consisted of two translations and back translations performed by two independent evaluators; an evaluation of the versions and the development of a synthetic version; and a commented pretest of the questionnaire. RESULTS: For each item of the instrument, the results of the four stages are reported. Most of the participants (91%) did not present any difficulties comprehending the items of the instrument. Further studies should be addressed to determine the adequacy of using this instrument in the less-educated population. We recommend that less instructed subjects be supervised while responding the questionnaire. DISCUSSION: The use of two translations versions, their critical appraisal and the assessment of the target population conceives more safety to the process of semantic equivalence.CONTEXTO: Atualmente há na literatura um crescente interesse na interface entre exercício físico e transtornos psiquiátricos. Apesar disso, ainda há uma deficiência de instrumentos de autorrelato para medir os níveis de atividade física dos pacientes. OBJETIVO: A tradução, a aferição da equivalência semântica e uma aplicação piloto (n = 30), sem pretensão psicométrica, do Questionário de Atividade Física Habitual, visando sua utilização na população brasileira de diferentes níveis de escolaridade. MÉTODOS: O processo envolveu duas traduções e retrotraduções realizadas por avaliadores independentes, avaliação das versões seguida da elaboração de uma versão síntese e pré-teste comentado. RESULTADOS: A maioria dos participantes (91%) não apresentou dificuldades de compreensão com o questionário. Para cada item do instrumento, apresentam-se os resultados das quatro etapas. Mais estudos são necessários para determinar a adequação para populações de baixa escolaridade. Os autores recomendam que sujeitos menos instruídos sejam supervisionados ao preencher o questionário. CONCLUSÕES: A utilização de duas versões de tradução e retrotradução, a discussão sobre a versão síntese e a interlocução com a população-alvo proporcionam maior segurança ao processo de equivalência semântica

Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data’s reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.Research supported by Barretos Cancer Hospital. EIP has a grant from FAPESP (FAPESP, SP, Brazil, #2013/24633-2). N Campacci is supported by a PhD fellowship from FAPESP (FAPESP, SP, Brazil, #2015/02444-9).info:eu-repo/semantics/publishedVersio

Genome-Wide Significant Risk Loci for Mood Disorders in the Old Order Amish Founder Population

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with \u3e2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that OOA-specific risk loci harbor novel risk-associated genes that interact with known neuropsychiatry-associated genes via gene interaction networks. Annotation of the variants at these risk loci revealed population-enriched, non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. Our findings provide insight into the genetic architecture of mood disorders and a substrate for mechanistic and clinical studies

Constituintes químicos de Vernonia scorpioides (Lam) Pers. (Asteraceae)

The chemical investigation of hexane and ethanol extracts from the aerial parts of Vernonia scorpioides resulted in the isolation and characterization of a new polyacetylene lactone, rel-4-dihydro-4β-hydroxy-5a-octa-2,4,6-triynyl-furan-2-(5H)-one, along with the new ethyl 3,4-dihydroxy-6,8,10-triynyl-dodecanoate, and seven known compounds: taraxasteryl acetate, lupeyl acetate, lupeol, lupenone, β-sitosterol, stigmasterol and luteolin. The structure of all compounds was determined by spectrometric techniques (HR-ESI-MS, ¹H and 13C NMR and IV) and comparison with published spectral data