Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

Anxious Personality and Breast Cancer: Possible Negative Impact on Quality of Life After Breast-Conserving Therapy

Background Quality of Life (QoL) is an important outcome measure in oncology. To assess the influence of surgical treatment and personality on QoL in women with breast cancer, a longitudinal prospective cohort study was done. Methods Women (n = 222) completed questionnaires concerning QoL (WHOQOL 100) and personality (NEO-FFI and STAI) prior to the diagnosis of breast cancer and 1, 3, 6, and 12 months after diagnosis and treatment. One hundred five women were treated with breast-conserving therapy (BCT) and 117 women underwent mastectomy (MTC). Results The two treatment groups did not differ on overall QoL. At all measurement times the influence of trait anxiety on overall QoL was substantial in the BCT group. Women with a high score on trait anxiety were seven times more likely to have a low overall QoL 1 year after BCT. In the MTC group overall QoL was influenced mainly by neuroticism. Conclusions Personality, especially trait anxiety and neuroticism, determined patients' overall QoL scores. Women with an anxious personality fared worse concerning QoL after breast conserving therap

STD-dependent and independent encoding of input irregularity as spike rate in a computational model of a cerebellar nucleus neuron

Copyright The Authors 2011. This article is published with open access at Springerlink.comNeurons in the cerebellar nuclei (CN) receive inhibitory inputs from Purkinje cells in the cerebellar cortex and provide the major output from the cerebellum, but their computational function is not well understood. It has recently been shown that the spike activity of Purkinje cells is more regular than previously assumed and that this regularity can affect motor behaviour. We use a conductance-based model of a CN neuron to study the effect of the regularity of Purkinje cell spiking on CN neuron activity. We find that increasing the irregularity of Purkinje cell activity accelerates the CN neuron spike rate and that the mechanism of this recoding of input irregularity as output spike rate depends on the number of Purkinje cells converging onto a CN neuron. For high convergence ratios, the irregularity induced spike rate acceleration depends on short-term depression (STD) at the Purkinje cell synapses. At low convergence ratios, or for synchronised Purkinje cell input, the firing rate increase is independent of STD. The transformation of input irregularity into output spike rate occurs in response to artificial input spike trains as well as to spike trains recorded from Purkinje cells in tottering mice, which show highly irregular spiking patterns. Our results suggest that STD may contribute to the accelerated CN spike rate in tottering mice and they raise the possibility that the deficits in motor control in these mutants partly result as a pathological consequence of this natural form of plasticity.Peer reviewedFinal Published versio

Stressors in Breast Cancer Post-Treatment: a Qualitative Approach Factores estresantes del post-tratamiento del cáncer de mama: un enfoque cualitativo Estressores pós-tratamento do câncer de mama: um enfoque qualitativo

With the increasing effectiveness of breast cancer treatment, the scientific interest in investigating the quality of life of survivors has increased. However, research addressing the post-treatment period is still scarce. The aim of this study was to identify the stressors present in the lives of women in the one to five years post-diagnosis period. The sample was composed of 16 women assisted at a specialized mastectomy rehabilitation service. Data were collected through semi-structured interviews and analyzed using content analysis. The results indicate conflicts with self-image and alteration in the feeling of autonomy, fear in relation to the evolution of the condition, feelings of guilt about the disorder generated in the family, experience of disturbing social situations and a desire to return to their professional occupation. These results reveal the existence of stressors in this phase and the importance of support offered by psychosocial rehabilitation services for this population.<br>Con la creciente resolutividad del tratamiento del cáncer de mama, ha aumentado el interés científico por la investigación de la calidad de vida de las sobrevivientes. Sin embargo, todavía son escasas las investigaciones que abordan el período post-tratamiento. Este estudio tuvo por objetivo identificar los factores estresantes presentes en la vida de mujeres en el período de uno a cinco años post-diagnóstico. Fueron investigadas 16 mujeres atendidas en un servicio especializado en rehabilitación de mastectomizadas. Los datos fueron recolectados mediante entrevista semiestructurada y analizados por medio del análisis de contenido. Los resultados indicaron conflictos con la autoimagen, alteración en la sensación de autosuficiencia, miedo en relación a la evolución del cuadro, sentimiento de culpa por el trastorno generado en la familia, vivencia de situaciones sociales perturbadoras y, deseo de retornar a la ocupación profesional. Esos resultados refuerzan la comprobación de la existencia de factores estresantes en esta fase y la importancia del apoyo ofrecido por los servicios de rehabilitación psicosocial junto a esa población.<br>Com a crescente resolutividade do tratamento do câncer de mama, tem aumentado o interesse científico pela investigação da qualidade de vida das sobreviventes. No entanto, ainda são escassas as pesquisas que abordam o período pós-tratamento. Este estudo teve por objetivo identificar os estressores presentes na vida de mulheres, no período de um a cinco anos pós-diagnóstico. Foram investigadas 16 mulheres, atendidas em um serviço especializado em reabilitação de mastectomizadas. Os dados foram coletados mediante entrevista semiestruturada e analisados por meio da análise de conteúdo. Os resultados indicaram conflitos com a autoimagem e alteração na sensação de autossuficiência, medo em relação à evolução do quadro, sentimento de culpa pelo transtorno gerado na família, vivência de situações sociais perturbadoras e desejo de retornar à ocupação profissional. Esses resultados reforçam a existência de estressores nessa fase e a importância do apoio oferecido pelos serviços de reabilitação psicossocial, junto a essa população