واکنش ایمنی ذاتی بین بیماری دو قطبی و اسکیزوفرنی دچار بی نظمی متفاوت است
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|30269||2015||7 صفحه PDF||سفارش دهید||محاسبه نشده|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Schizophrenia Research, Volume 161, Issues 2–3, February 2015, Pages 215–221
Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1, CCR5/HCST, C1QA/CD68, CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1, CCR5 and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia.
Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions, with a lifetime prevalence of about 1% (Merikangas et al., 2007, Alaerts and Del-Favero, 2009 and Doherty et al., 2012). Both disorders have a neurodevelopment component, with onset of symptoms occurring most frequently during late adolescence or early adulthood (Maier et al., 2006 and Doherty et al., 2012). Family studies demonstrate that the recurrence risk in families of SZ patients is 8-12% and the recurrence risk in BD families is approximately 10% (Barnett and Smoller, 2009 and Ivleva et al., 2010). The estimates of heritability range between 40 - 80% for both diseases (Sullivan et al., 2003 and Bienvenu et al., 2011) with genetic findings indicating an overlap in familial-genetic susceptibility across the diseases (O'Donovan, et al., 2008, Lichtenstein et al., 2009 and Ivleva et al., 2010). In addition, chromosomal regions, including risk variants show linkage to both BD and SZ (Barnett and Smoller, 2009, Moskvina et al., 2009, Williams et al., 2011a and Williams et al., 2011b). Global gene expression analyses revealed common genes for SZ and BD, which were associated with synapse, neuronal and glial functions, metabolism, cellular and mitochondrial function, nervous system development, immune system development and response, and cell death (Iwamoto et al., 2005, Choi et al., 2008, Shao and Vawter, 2008 and Lin et al., 2012). Due to the similarities between both disorders, gene expression profiling of BD and SZ were first compared as one entity to controls to identify common alterations. Further, genes from this comparison were analyzed in co-expression and protein-protein interaction (PPI) networks contexts allowing the identification of changes in expression and biological processes potentially involved in the different clinical phenotypes observed in SZ and BD.