Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Affective state dependence and relative trait stability of perfectionism in sleep disturbances / Dependência do estado afetivo e estabilidade relativa do traço do perfeccionismo nas perturbações de sono

OBJECTIVE: To evaluate the degree of absolute change, relative stability and state dependence of trait perfectionism in sleep disturbances in a sample of university students. METHOD: Participants completed the Multidimensional Perfectionism Scale and two items concerning sleep difficulties. The mean age at T0 (baseline) was 19.59 years (SD = 1.61, range = 17-25) and 62.5 percent of the sample were female. RESULTS: Absolute changes in self-oriented and socially-prescribed perfectionism were found. Relative stability was found for all perfectionism dimensions. Prior and concurrent sleep disturbances explained a significant amount of variance in perfectionism. Controlling for the effects of sleep measures, prior self-oriented perfectionism and other-oriented perfectionism were the only significant predictors of subsequent self-oriented perfectionism and other-oriented perfectionism, at T1 and T2. Difficulties falling asleep at T1 and socially-prescribed perfectionism at T0 were significant predictors of socially-prescribed perfectionism at T1. CONCLUSION: Despite significant changes in perfectionism mean scores over the follow-up, the correlation analyses demonstrated that participants remained quite stable in regard to their relative levels of perfectionism. As concurrent difficulties initiating sleep also predicted concurrent socially-prescribed perfectionism, this seems to be one dimension of perfectionism with trait-state characteristics.

OBJETIVOS: Avaliar o grau de mudança absoluta, de estabilidade relativa e dependência do estado do perfeccionismo nas perturbações de sono numa amostra de estudantes universitários. MÉTODO: Os sujeitos completaram a Escala Multidimensional do Perfeccionismo e dois itens sobre dificuldades em dormir. Os dados foram recolhidos em três momentos de avaliação, separados por um intervalo de um ano acadêmico. A idade média dos sujeitos no T0 era de 19,59 anos (DP = 1,61, variação = 17-25); 62,5 por cento eram mulheres. RESULTADOS: Foram encontradas ao longo do follow-up mudanças absolutas para o perfeccionismo auto-orientado e para o perfeccionismo socialmente prescrito. Foi encontrada estabilidade relativa para todas as dimensões do perfeccionismo. As dificuldades de sono prévias e concorrentes explicaram significativamente a variância do perfeccionismo. Controlando o efeito das dificuldades em dormir, o perfeccionismo auto-orientado e o perfeccionismo orientado para o outro prévios foram os únicos preditores significativos de perfeccionismo auto-orientado e perfeccionismo orientado para o outro (T1 e T2). As dificuldades em iniciar o sono no T1 e o perfeccionismo socialmente prescrito prévio (T0) revelaram-se preditores significativos de perfeccionismo socialmente prescrito no T1. CONCLUSÃO: Apesar das mudanças significativas nas pontuações médias de perfeccionismo ao longo do follow-up, as análises de correlação demonstraram que os participantes permaneceram relativamente estáveis nos seus níveis de perfeccionismo. Uma vez que as dificuldades em iniciar o sono concorrentes se revelaram um preditor significativo de perfeccionismo socialmente prescrito, esta é a dimensão do perfeccionismo que possui características traço-estado.

Human p53 tumor suppressor gene (TP53) and schizophrenia: case-control and family studies.

The human p53 tumor suppressor gene (TP53) is considered as a candidate susceptibility gene for schizophrenia because of its functions in neurodevelopment. To test for an association between TP53 and schizophrenia, both the case-control study and the transmission disequilibrium test (TDT) were performed on genotype data from eight polymorphisms in TP53. Our samples included 286 Toronto schizophrenia cases and 264 controls, and 163 Portuguese nuclear families. In the Toronto case-control study significant differences of allele frequencies of the CAA Ins/Del (p=0.027) and the 16bp Ins/Del (p=0.022) were detected. In TDT analysis we found significant differences for transmission of the CAA Ins/Del (p=0.017) in Portuguese schizophrenia families. Haplotype analysis also showed a significant association between TP53 and schizophrenia. These results provide further evidence that TP53 may play a role in the pathogenesis of schizophrenia.