Os episódios mistos em pacientes portadores de Transtorno Bipolar são descritos freqüentemente como sendo mais graves que os episódios de mania aguda. Além disso, muitos trabalhos na literatura descrevem os pacientes com TB com história de episódios mistos, como um grupo distinto clínica e demograficamente do grupo com apresentação apenas de episódios de mania pura. Os objetivos deste estudo foram comparar clinicamente episódios agudos mistos versus episódios de mania pura e comparar clínica e demograficamente pacientes que apresentaram em algum momento do seguimento clínico pelo menos um episódio misto com pacientes que apresentaram apenas mania pura. Vinte pacientes apresentando episodio de mania pura foram comparados a 29 pacientes em estado misto de acordo com os critérios do DSM-IV. Não houve diferença na duração destes episódios, presença de hospitalização e tentativas de suicídio. Na comparação dos dados demográficos, não encontramos diferenças na idade, distribuição entre os sexos, classe sócio-econômica, estado civil e anos de escolaridade. Em relação ao curso, nosso estudo mostrou que pacientes com pelo menos um estado misto apresentaram maior freqüência de tentativas de suicídio e de episódios, mais comorbidades e idade de início da doença mais precoce. Foi realizada analise multivariada através de regressão logística para a identificação das variáveis clinicas que melhor distinguem um grupo do outro. Esta analise mostrou que a presença de comorbidades e de tentativas de suicídio foram as variáveis identificadas que mais fortemente estão associadas ao diagnóstico de pacientes com estado misto. / Mixed episodes in patients with bipolar disorder (BD) have been frequently described as more severe than acute manic episodes. Moreover, many papers in the literature have described the patients with BD with history of mixed episodes as a group that is clinically and demographically distinct from the group with clinical presentation of pure manic episodes. The purposes of this study were to compare clinically acute mixed episodes with pure manic episodes and compare clinically and demographically patients that present in any moment of their clinical follow-up at least one mixed episode with patients that present only pure mania. Twenty patients with pure manic episode were compared to 29 patients with mixed episodes according to DSM-IV criteria. There were no differences in episodes duration, presence of hospitalization and suicide attempts. Comparing the demographic data, we did not find differences in age, gender distribution, socio-economic status, marital status and years of education. Regarding the course of illness, our study showed that patients with at least one mixed state presented higher frequency of suicide attempts, younger age of illness onset, more co-morbidities, and higher index of impulsivity. A multi-variate analysis was performed with logistic regression to identify the clinical variables that better distinguish one group from the other. This analysis showed that the presence of co-morbidities and suicide attempts were the identified variables that are strongly associated with the diagnosis of patients with mixed state.

Introdução: O transtorno obsessivo-compulsivo (TOC) é uma doença de etiologia complexa, podendo ser influenciada por inúmeros fatores genéticos e ambientais. A falta de homogeneidade na descrição do transtorno dificulta a pesquisa de fatores etiológicos. Um dos subgrupos de TOC com características mais homogêneas é o TOC de início precoce. O objetivo principal deste estudo é investigar o efeito da idade de início dos diversos sintomas nas características clínicas dos transtornos psiquiátricos do Eixo I na trajetória evolutiva de pacientes com TOC. Metodologia: 1001 pacientes com TOC de acordo com os critérios do DSM-IV foram avaliados de forma direta com os instrumentos: Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos (DY-BOCS), Escala Yale-Brown de Sintomas Obsessivo-Compulsivos (Y-BOCS), Entrevista Clínica Estruturada para o DSM-IV - Transtornos do Eixo I (SCID-I/P), Inventários de Ansiedade e de Depressão de Beck, Questionário de História Natural do TOC e Escala de Crenças de Brown. Para comparação das variáveis categoriais foram realizados os testes qui-quadrado e para variáveis numéricas testes não paramétricos de Kruskal-Wallis e testes paramétricos tipo ANOVA. Foram considerados para todos os testes nível de significância de 5%. O estudo das idades de início das comorbidades foi realizado utilizando a abordagem bayesiana. Resultados: Pacientes com início precoce tiveram maior frequência de Ansiedade de Separação (p<0,001); Transtorno de Déficit de Atenção e Hiperatividade (p=0,031); Tiques (p=0,009); Espectro Obsessivo-Compulsivo (OC) (p<0,001); Transtornos do Impulso (p=0,005); e do Humor (p=0,020). Além disso, tiveram maior gravidade em todas as medidas de escore nas escalas Y-BOCS (p<0,001) e DY-BOCS (p<0,001), curso com piora progressiva do TOC (p<0,001) e maior frequência de história familiar de TOC (p<0,001) e transtornos de Tiques (p=0,013). Pacientes com TOC que apresentaram ansiedade de separação como primeiro diagnóstico tiveram uma tendência a apresentar maior frequência de: Transtornos Ansiosos (p=0,058), Somatoformes (p=0,056), TEPT (p=0,004), maior gravidade na dimensão Sexual/Religioso (p=0,053) e escores mais elevados nas escalas Beck depressão (p=0,005) e Beck ansiedade (p<0,001). Pacientes com TOC que apresentaram TDAH como primeiro diagnóstico tiveram maior frequência de Abuso de Substância (p<0,001) e apresentaram um curso com piora mais progressiva do TOC comparados com os outros grupos (p=0,033). Pacientes com TOC que apresentaram transtornos de tiques como primeiro diagnóstico tiveram maior frequência de Transtornos do Espectro OC (p=0,034). Conclusão: O TOC é um transtorno heterogêneo que pode compreender diversos subtipos de acordo com a abordagem escolhida / Introduction: Obsessive-Compulsive Disorder (OCD) has a complex etiology, and can be influenced by several genetic and environmental factors. The lack of homogeneity in the description of the disorders complicates the search for etiological factors. The main goal of this study is to verify the effect of age at onset of several symptoms in the clinical characteristics of Axis I psychiatric disorders in the trajectory of OCD patients. Methodology: 1,001 consecutive OCD patients were evaluated at a single time point. Standardized instruments were used: Structured Clinical Interview for Diagnosis of Axis I, according to DSM-IV and for impulse-control disorders; Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Beck Depression and Anxiety Inventories and Brown Beliefs assessment Scale; and the Natural History Questionnaire. Chi-square test was used for categorical variables, and Kruskal-Wallis and ANOVA tests were used for continuous variables. For all the tests the significant level was considered p <.05. To analyze the distribution of comorbidities according to age at onset a Bayesian approach was used. Results: Patients with early age at onset had higher frequency of separation anxiety disorder (p<0.001), attention deficit hyperactivity disorder (ADHD) (p=0.031); tic disorders (p<0.009); obsessive-compulsive spectrum disorders (p<0.001); impulse-control disorders (p=0.005) and mood disorders (p=0.020). Besides, they presented higher severity of all measures of Y-BOCS score (p<0.001) and DY-BOCS score (p<0.001), OCD course with progressive worsening (p<0.001) and higher frequency of family history of OCD (p<0.001) and tic disorders (p=0.013). OCD patients who presented separation anxiety disorder as the first manifested diagnosis had higher frequencies of: anxiety disorders (p=0.058), somatoform disorders (p=0.056), post-traumatic stress disorder (p=0.004), higher frequency of Sexual/Religious dimension (p=0.053) and higher scores on Beck depression (p=0.005) and Beck anxiety (p<0.001). OCD patients who presented ADHD as first manifested diagnosis presented higher frequency of substance abuse (p<0.001) and presented more OCD course with progressive worsening (p=0.033). OCD patients who presented tic disorder as first manifested diagnosis presented higher frequency of OC spectrum disorders (p=0.034). Conclusion: We can conclude that OCD is a heterogeneous disorder and may include several subtypes according to the chosen approach

Introdução: O transtorno obsessivo-compulsivo (TOC) é uma doença de etiologia complexa, podendo ser influenciada por inúmeros fatores genéticos e ambientais. A falta de homogeneidade na descrição do transtorno dificulta a pesquisa de fatores etiológicos. Um dos subgrupos de TOC com características mais homogêneas é o TOC de início precoce. O objetivo principal deste estudo é investigar o efeito da idade de início dos diversos sintomas nas características clínicas dos transtornos psiquiátricos do Eixo I na trajetória evolutiva de pacientes com TOC. Metodologia: 1001 pacientes com TOC de acordo com os critérios do DSM-IV foram avaliados de forma direta com os instrumentos: Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos (DY-BOCS), Escala Yale-Brown de Sintomas Obsessivo-Compulsivos (Y-BOCS), Entrevista Clínica Estruturada para o DSM-IV - Transtornos do Eixo I (SCID-I/P), Inventários de Ansiedade e de Depressão de Beck, Questionário de História Natural do TOC e Escala de Crenças de Brown. Para comparação das variáveis categoriais foram realizados os testes qui-quadrado e para variáveis numéricas testes não paramétricos de Kruskal-Wallis e testes paramétricos tipo ANOVA. Foram considerados para todos os testes nível de significância de 5%. O estudo das idades de início das comorbidades foi realizado utilizando a abordagem bayesiana. Resultados: Pacientes com início precoce tiveram maior frequência de Ansiedade de Separação (p<0,001); Transtorno de Déficit de Atenção e Hiperatividade (p=0,031); Tiques (p=0,009); Espectro Obsessivo-Compulsivo (OC) (p<0,001); Transtornos do Impulso (p=0,005); e do Humor (p=0,020). Além disso, tiveram maior gravidade em todas as medidas de escore nas escalas Y-BOCS (p<0,001) e DY-BOCS (p<0,001), curso com piora progressiva do TOC (p<0,001) e maior frequência de história familiar de TOC (p<0,001) e transtornos de Tiques (p=0,013). Pacientes com TOC que apresentaram ansiedade de separação como primeiro diagnóstico tiveram uma tendência a apresentar maior frequência de: Transtornos Ansiosos (p=0,058), Somatoformes (p=0,056), TEPT (p=0,004), maior gravidade na dimensão Sexual/Religioso (p=0,053) e escores mais elevados nas escalas Beck depressão (p=0,005) e Beck ansiedade (p<0,001). Pacientes com TOC que apresentaram TDAH como primeiro diagnóstico tiveram maior frequência de Abuso de Substância (p<0,001) e apresentaram um curso com piora mais progressiva do TOC comparados com os outros grupos (p=0,033). Pacientes com TOC que apresentaram transtornos de tiques como primeiro diagnóstico tiveram maior frequência de Transtornos do Espectro OC (p=0,034). Conclusão: O TOC é um transtorno heterogêneo que pode compreender diversos subtipos de acordo com a abordagem escolhida / Introduction: Obsessive-Compulsive Disorder (OCD) has a complex etiology, and can be influenced by several genetic and environmental factors. The lack of homogeneity in the description of the disorders complicates the search for etiological factors. The main goal of this study is to verify the effect of age at onset of several symptoms in the clinical characteristics of Axis I psychiatric disorders in the trajectory of OCD patients. Methodology: 1,001 consecutive OCD patients were evaluated at a single time point. Standardized instruments were used: Structured Clinical Interview for Diagnosis of Axis I, according to DSM-IV and for impulse-control disorders; Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Beck Depression and Anxiety Inventories and Brown Beliefs assessment Scale; and the Natural History Questionnaire. Chi-square test was used for categorical variables, and Kruskal-Wallis and ANOVA tests were used for continuous variables. For all the tests the significant level was considered p <.05. To analyze the distribution of comorbidities according to age at onset a Bayesian approach was used. Results: Patients with early age at onset had higher frequency of separation anxiety disorder (p<0.001), attention deficit hyperactivity disorder (ADHD) (p=0.031); tic disorders (p<0.009); obsessive-compulsive spectrum disorders (p<0.001); impulse-control disorders (p=0.005) and mood disorders (p=0.020). Besides, they presented higher severity of all measures of Y-BOCS score (p<0.001) and DY-BOCS score (p<0.001), OCD course with progressive worsening (p<0.001) and higher frequency of family history of OCD (p<0.001) and tic disorders (p=0.013). OCD patients who presented separation anxiety disorder as the first manifested diagnosis had higher frequencies of: anxiety disorders (p=0.058), somatoform disorders (p=0.056), post-traumatic stress disorder (p=0.004), higher frequency of Sexual/Religious dimension (p=0.053) and higher scores on Beck depression (p=0.005) and Beck anxiety (p<0.001). OCD patients who presented ADHD as first manifested diagnosis presented higher frequency of substance abuse (p<0.001) and presented more OCD course with progressive worsening (p=0.033). OCD patients who presented tic disorder as first manifested diagnosis presented higher frequency of OC spectrum disorders (p=0.034). Conclusion: We can conclude that OCD is a heterogeneous disorder and may include several subtypes according to the chosen approach

Prevalence findings for 1995 of illicit drug use as well as DSM-IV abuse and dependence are reported from a representative population sample of 3,021 respondents from Munich, Germany, aged 14–24 years. Results are based on personal interviews using the M-Composite International Diagnostic Interview (M-CIDI) with its DSM-IV diagnostic algorithms. Findings indicate that more than 30% of the adolescents and young adults are or have been using one or more illicit drugs at least once in their life. Men were slightly more likely to ever use drugs and used them more frequently than women. Cannabinoids were by far the most frequently used type of drug, followed by various stimulating drugs and hallucinogens. There is also considerable polysubstance use among 14- to 24-year-olds. Criteria for DSM-IV abuse without dependence were met by 4.1% of all men and 1.8% of all women, a dependence syndrome of any type of illicit drug was diagnosed in 2.5% of the men and 1.6% of the women. Cumulative age of onset incidence analyses suggest that substance use starts early, in about one-third before the age of 16 years and continues to rise for most drugs throughout adolescence and young adulthood. Overall these findings suggest that substance use and substance disorders are more prevalent than suggested in most previous German studies.

Schizophrenia (SCZ) is a debilitating disorder with a prevalence of approximately 1 % worldwide. SCZ is known to have a high degree of genetic and clinical heterogeneity and is a major health problem worldwide. The integrin-β 3 subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric disorders. We therefore hypothesized that ITGB3 gene polymorphisms might also play a role in SCZ and age at onset (AAO) of SCZ. We investigated the genetic associations of 23 single-nucleotide polymorphisms (SNPs) of the ITGB3 gene with AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear regression analysis and meta-analysis. We observed four ITGB3-SNPs associated with AAO in SCZ in a non-Genetic Association Information Network (GAIN) sample (p < 10-3). Three of these four SNPs were replicated in the GAIN sample. The SNP rs16941771 was most significantly associated with AAO (p = 7.47 × 10-5). Meta-analysis showed that 6 of 23 SNPs were associated with AAO. The haplotype analysis also supports the association of ITGB3 with AAO. Three disease-associated SNPs were located at species-conserved regions, indicating functional importance. This is the first report which shows that ITGB3 variants are associated with AAO in SCZ, providing direct evidence of the use of AAO as an intermediate phenotype to dissect the complex genetics of SCZ.

Schizophrenia (SCZ) is a debilitating disorder with a prevalence of approximately 1 % worldwide. SCZ is known to have a high degree of genetic and clinical heterogeneity and is a major health problem worldwide. The integrin-β 3 subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric disorders. We therefore hypothesized that ITGB3 gene polymorphisms might also play a role in SCZ and age at onset (AAO) of SCZ. We investigated the genetic associations of 23 single-nucleotide polymorphisms (SNPs) of the ITGB3 gene with AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear regression analysis and meta-analysis. We observed four ITGB3-SNPs associated with AAO in SCZ in a non-Genetic Association Information Network (GAIN) sample (p < 10-3). Three of these four SNPs were replicated in the GAIN sample. The SNP rs16941771 was most significantly associated with AAO (p = 7.47 × 10-5). Meta-analysis showed that 6 of 23 SNPs were associated with AAO. The haplotype analysis also supports the association of ITGB3 with AAO. Three disease-associated SNPs were located at species-conserved regions, indicating functional importance. This is the first report which shows that ITGB3 variants are associated with AAO in SCZ, providing direct evidence of the use of AAO as an intermediate phenotype to dissect the complex genetics of SCZ.

No description available.

Alzheimer's disease (AD), the most common form of dementia, is a chronic neurodegenerative disease. The HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene is expressed in human brain and may play a role in the pathogenesis of neurodegenerative disorders. Till now, no previous study has reported the association of the HACE1 gene with the risk and age at onset (AAO) of AD; while few studies have checked the proportional hazards assumption in the survival analysis of AAO of AD using Cox proportional hazards model. In this study, we examined the associations of 14 single nucleotide polymorphisms (SNPs) in the HACE1 gene with the risk and the AAO of AD using 791 AD patients and 782 controls. Multiple logistic regression model identified one SNP (rs9499937 with p = 1.8×10) to be associated with the risk of AD. For survival analysis of AAO, both classic Cox regression model and Bayesian survival analysis using the Cox proportional hazards model were applied to examine the association of each SNP with the AAO. The hazards ratio (HR) with its 95% confidence interval (CI) was estimated. Survival analysis using the classic Cox regression model showed that 4 SNPs were significantly associated with the AAO (top SNP rs9499937 with HR=1.33, 95%CI=1.13-1.57, p=5.0×10). Bayesian Cox regression model showed similar but a slightly stronger associations (top SNP rs9499937 with HR=1.34, 95%CI=1.11-1.55) compared with the classic Cox regression model. Using an independent family-based sample, one SNP rs9486018 was associated with the risk of AD (p=0.0323) and the T-T-G haplotype from rs9786015, rs9486018 and rs4079063 showed associations with both the risk and AAO of AD (p=2.27×10 and 0.0487, respectively). The findings of this study provide first evidence that several genetic variants in the HACE1 gene were associated with the risk and AAO of AD.

<p dir="ltr">Bilingualism and language acquisition research continually struggle with discerning the disparities and resemblances between heritage speakers and second language learners. Both groups draw considerable attention due to their unique language acquisition trajectories. This study investigates potential differences or similarities between heritage speakers and L2 learners of Spanish in their acquisition of syntax-semantics interface areas, focusing on the present perfect.</p><p dir="ltr">The present perfect denotes a past event relevant to the present, primarily establishing a connection between a current state and a preceding situation. However, it is imperative to note that the present perfect, often confused with the perfect aspect, encompasses more than this singular function. It represents merely one aspect within the perfect aspect, encompassing various other uses and functions beyond merely expressing present relevance to past events.</p><p dir="ltr">Despite extensive scholarly interest in studying heritage speakers (HS), including examinations of their distinctive morpho-syntax and aspectual challenges, limited literature exists regarding their utilization of the present perfect, frequently assumed to mirror its English counterpart. The intricate nuances in grammatical aspect when employing the present perfect remain largely unexplored.</p><p dir="ltr">This study aims to investigate the production and intuition of the aspectual values of the present perfect tense by Spanish heritage speakers and Spanish L2 learners, assessing potential divergences between the two groups given their differing levels of language exposure. To achieve this, an elicited production task and an acceptability judgment task will be employed to triangulate the participants' usage and comprehension of the target structure in various contexts.</p><p><br></p>

O câncer de mama em mulheres jovens (idade igual ou abaixo de 35 anos) apresenta-se de forma mais avançada ao diagnóstico, possuindo grau histopatológico menos diferenciado. Além disso, as pacientes apresentam maior taxa de mortalidade e menor sobrevida livre de doença quando comparadas às pacientes menopausadas. Dentre os cânceres de mama em mulheres jovens, apenas 8 a 10% dos casos familiais estão relacionados a mutações nos genes BRCA1 e BRCA2 e esta frequência nos casos esporádicos é ainda menor (3- 10%). Assim, os fatores relacionados à desregulação oncogênica em mulheres jovens com ou sem antecedentes familiares que apresentam testes genéticos negativos para essas mutações não estão suficientemente esclarecidos. Tais evidências sugerem que o câncer em mulheres muito jovens apresenta características biológicas especificas. Considerando que a expressão gênica é regulada em múltiplos níveis, alguns estudos recentes tem referido a importância dos microRNAs neste processo tanto na degradação de RNAs mensageiros como na repressão da tradução. A análise da expressão dos microRNAs em câncer de mama tem revelado perfis característicos de determinados níveis de progressão da doença. No presente trabalho, nosso objetivo foi determinar o perfil de expressão de microRNAs em tumores de mama de mulheres jovens (idade igual ou abaixo de 35 anos) não-portadoras de mutações nos genes BRCA1/2. As pacientes foram subdivididas em 2 grupos [familial (n=8) e não-familial (n=20)] e, em seguida, os dados de expressão foram comparados aos obtidos em amostras normais de mamoplastia. A quantificação da expressão dos microRNAs foi realizada pela reação de RT-PCR em tempo real, utilizando o sistema TaqMan microRNA Assay. As análises estatísticas mostraram 246 miRNAs de expressão diferencial entre os 3 grupos (normal, familial e não-familial) sendo que, destes, encontramos 137 miRNAs diferencialmente expressos entre os grupos familial e normal; 44 miRNAs entre os grupos não-familial e normal e 4 miRNAs entre os grupos familial e não-familial. Nossos dados demonstram que os tumores do grupo de pacientes familiais quando comparados aos normais apresentam um perfil de miRNAs globalmente reduzido. O perfil de expressão de miRNAs no grupo de pacientes com câncer de mama esporádico é pouco distinto do grupo com história familial. Muitos dos miRNAs com expressão reduzida estavam envolvidos, de acordo com a literatura, numa sinalização comum relacionada a mecanismos de proliferação, apoptose e invasão celular. Os 4 miRNAs identificados como diferencialmente expressos entre os grupos familial e nãofamilial embora relacionados com outros tipos de cancer precisam de uma melhor caracterização em cancer de mama / A rise in the incidence of breast cancer among young adult women (with age 35) was observed in recent decades. Breast cancer incidence in young woman has been correlated to poor survival and aggressive features. Due to different type of breast cancers in young woman, 8- 10% with familial history appears with mutation in BRCA1/2 genes, and similar proportion occurs in cases without familial history (3- 10%). However, early onset breast cancer patients with or without familial history, non carriers of BRCA1/BRCA2 mutations is not well elucidated. The deregulation by microRNAs has recently emerged as a major determinant of tumorigenesis. Because miRNAs function by targeting functionally important protein-conding genes, it is of outstanding interest to identify miRNAs involved in the molecular mechanism underlying aggressiveness in tumors of young patients that might represent biomarkers and therapeutic targets. This evidence suggests that breast cancer in young woman has specific biological characteristics. Understanding the patterns of miRNAs expression that potentially alter the regulation of key breast cancer genes we could give a better treatment to these patients. Thirty-two patients were selected: 8 with familial history of breast and ovarian suggestive of hereditary condition according to NCCN criteria and 20 without familial history. Patients of both groups were of non carriers of BRCA1/BRCA2 mutations. The determination of microRNA expression network between those 2 groups was performed by TaqMan microRNA Assay (Applied Biosystems) using as control 3 normal mamoplastia samples from wealthy young women. Data were normalized using endogenous miRNA presented in each array. Statistical comparisons were done using ANOVA and Student T test with adjusted FDR (5%). It was found that 246 miRNAs were differently expressed between the 3 groups. From the comparison of familial group against normal group it was found 137 miRNAs differently expressed. In the comparison between non familial and normal group it was found 44 miRNAs differently expressed. Finally the comparison between familial group and non familial group it was found 4 miRNAs differently expressed. Among these miRNAs are some which was well characterized in breast cancer with down-regulation such as: miR-125b, miR-126 and miR-100. Our findings suggested that tumors from familial or sporadic cases presented discrete differences of microRNA expression patterns. A global downregulation of 137 miRNAs in tumors from familial group of patients when compared to normal group was observed. Based on the literature, most of these miRNAs are related to mechanisms of proliferation, cells migration and apoptosis. To our knowledge, this is the first evidence of miRNA expression in tumors of early onset Breast Cancer patients, non carries BRCA1/2 mutation, providing insights that may lead to the detection of new conducts of treatment