روشی جدید برای #تشخیص #پاسخدهی #مبتلایان به #اختلال #دوقطبی (#BD) به #لیتیوم
#Neurons #derived from #patients with bipolar disorder divide into intrinsically different sub-populations of neurons, #predicting the patients’ #responsiveness to #lithium
🔍🖌پژوهشگران انستیتو #سالک در لاجولا کالیفرنیا 🇺🇸 به تازگی روشی ابداع نموده اند که بر اساس آن می توان با دقتی بیش از 92% پاسخدهی مبتلایان به اختلال دوقطبی (BD) را به داروی #کربنات #لیتیوم (#اسکالیت) مشخص ساخت؛ ذکر این نکته مهم است که تنها 30% مبتلایان به BD به ترکیبات لیتیوم پاسخ می دهند. فقط در ایالات متحده امریکا بیش از 5 میلیون نفر مبتلا به BD هستند.
🔬پژوهش های پیشین این پژوهشگران مشخص ساخته بود در افراد دارای BD #نورون های #شکنج دندانه ای #هیپوکامپ نسبت به افراد غیر بیمارِ عادی تحریک پذیرترند. در گام بعدی پژوهشگران نوع و الگوهای تحریک پذیری عصبی این افراد و نیز پاسخدهی آنها به لیتیوم را مشخص ساختند. بر پایه نتایج پژوهش فعلی تنها با بررسی سلول های #لمفوسیت B می توان پاسخ دهی افراد به لیتیوم را مشخص ساخت.
Abstract
#Bipolar disorder (#BD) is a #progressive #psychiatric disorder with more than 3% #prevalence worldwide. Affected individuals experience recurrent episodes of #depression and #mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and #genetic #heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that #hippocampal #dentate #gyrus (#DG) #neurons differentiated from induced pluripotent stem cell (#iPSC)-derived #fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from #Epstein–Barr #virus-immortalized #B_lymphocytes to verify that the hyperexcitability of #DG-like neurons is reproduced in this different cohort of patients and #cells. #Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. #Extensive #functional #analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from #lithium (Li)-responsive (LR) #patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different #subdisorders. Training a #Naïve #Bayes #classifier with the #electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, #fast #after-hyperpolarization (#AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, #sustained #spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.
لینک منبع 👇🏻(further reading)👇🏻
http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016260a.html
✅(در صورت جذابیت و علاقمندی به موضوع، مطلب را برای دیگران نیز بازنشر فرمایید).
📢کانال #دکترامیرمحمدشهسوارانی
🍃🌹🌸💐🌸🌹🍃
@DrAmirMohammadShahsavarani
#Neurons #derived from #patients with bipolar disorder divide into intrinsically different sub-populations of neurons, #predicting the patients’ #responsiveness to #lithium
🔍🖌پژوهشگران انستیتو #سالک در لاجولا کالیفرنیا 🇺🇸 به تازگی روشی ابداع نموده اند که بر اساس آن می توان با دقتی بیش از 92% پاسخدهی مبتلایان به اختلال دوقطبی (BD) را به داروی #کربنات #لیتیوم (#اسکالیت) مشخص ساخت؛ ذکر این نکته مهم است که تنها 30% مبتلایان به BD به ترکیبات لیتیوم پاسخ می دهند. فقط در ایالات متحده امریکا بیش از 5 میلیون نفر مبتلا به BD هستند.
🔬پژوهش های پیشین این پژوهشگران مشخص ساخته بود در افراد دارای BD #نورون های #شکنج دندانه ای #هیپوکامپ نسبت به افراد غیر بیمارِ عادی تحریک پذیرترند. در گام بعدی پژوهشگران نوع و الگوهای تحریک پذیری عصبی این افراد و نیز پاسخدهی آنها به لیتیوم را مشخص ساختند. بر پایه نتایج پژوهش فعلی تنها با بررسی سلول های #لمفوسیت B می توان پاسخ دهی افراد به لیتیوم را مشخص ساخت.
Abstract
#Bipolar disorder (#BD) is a #progressive #psychiatric disorder with more than 3% #prevalence worldwide. Affected individuals experience recurrent episodes of #depression and #mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and #genetic #heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that #hippocampal #dentate #gyrus (#DG) #neurons differentiated from induced pluripotent stem cell (#iPSC)-derived #fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from #Epstein–Barr #virus-immortalized #B_lymphocytes to verify that the hyperexcitability of #DG-like neurons is reproduced in this different cohort of patients and #cells. #Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. #Extensive #functional #analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from #lithium (Li)-responsive (LR) #patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different #subdisorders. Training a #Naïve #Bayes #classifier with the #electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, #fast #after-hyperpolarization (#AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, #sustained #spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.
لینک منبع 👇🏻(further reading)👇🏻
http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016260a.html
✅(در صورت جذابیت و علاقمندی به موضوع، مطلب را برای دیگران نیز بازنشر فرمایید).
📢کانال #دکترامیرمحمدشهسوارانی
🍃🌹🌸💐🌸🌹🍃
@DrAmirMohammadShahsavarani
♻️ارتباط معکوس بین #اسکیزوفرنی و #ورم مفاصل (#آرتریت رماتوئید)
#Generating testable #hypotheses for #schizophrenia and #rheumatoid arthritis #pathogenesis by integrating #epidemiological, #genomic, and #protein interaction data
پژوهشگران روانپزشکی و اطلاعات بایومدیکال دانشگاه پیتسبورگ 🇺🇸 در پژوهشی که با تازگی منتشر شده است با بررسی های #ژنومی، #همه گیری شناختی، و تعامل #پروتئینی دریافتند که #خطای ژنتیکی منجر به آرتریت رماتوئید و اسکیزوفرنی در نواحی مشابهی از #ژنوم افراد ایجاد می شود.
🔬پیمایش های آمار حیاتی مشخص ساخته اند که در افراد مبتلا به اسکیزوفرنی و خویشاوندان آنها شیوع #رماتوئیدآرتریت به طرز معناداری از جمعیت کلی کمتر است. در پژوهش حاضر آنالیز داده های ژنتیک، به محدوده ای به نام #HLA دست یافت که #ژن های #HLA-B, #TNXB, #NOTCH4, #HLA-C, #HCP5, #MICB, #PSORS1C1, و #C6orf10 در آن قرار دارند. همچنین مشخص شد HLA-B و HLA-C بیشترین دخالت را هم در رماتوئیدآرتریت و هم در اسکیزوفرنی دارند.
Abstract
#Patients with #schizophrenia and their relatives have reduced prevalence of #rheumatoid_arthritis. Schizophrenia and rheumatoid arthritis #genome-wide association studies also indicate negative genetic correlations, suggesting that there may be shared #pathogenesis at the #DNA level or downstream. A portion of the inverse prevalence could be attributed to #pleiotropy, i.e., variants of a single #nucleotide #polymorphism that could confer differential risk for these disorders. To study the basis for such an #interrelationship, we initially compared lists of single nucleotide polymorphisms with significant #genetic associations (p < 1e-8) for schizophrenia or rheumatoid arthritis, evaluating patterns of #linkage #disequilibrium and apparent #pleiotropic risk profiles. Single nucleotide polymorphisms that conferred risk for both schizophrenia and rheumatoid arthritis were localized solely to the extended #HLA region. Among single nucleotide polymorphisms that conferred differential risk for schizophrenia and rheumatoid arthritis, the majority were localized to #HLA-B, #TNXB, #NOTCH4, #HLA-C, #HCP5, #MICB, #PSORS1C1, and #C6orf10; published functional data indicate that HLA-B and HLA-C have the most plausible pathogenic roles in both disorders. #Interactomes of these eight genes were constructed from protein–protein interaction information using publicly available databases and novel #computational #predictions. The genes harboring apparently pleiotropic single nucleotide polymorphisms are closely connected to rheumatoid arthritis and schizophrenia associated genes through common interacting partners. A separate and independent analysis of the interactomes of rheumatoid arthritis and schizophrenia genes showed a significant overlap between the two interactomes and that they share several common pathways, motivating functional studies suggesting a relationship in the #pathogenesis of schizophrenia/rheumatoid arthritis.
لینک منبع 👇🏻(further reading)👇🏻
https://www.nature.com/articles/s41537-017-0010-z
✅(در صورت جذابیت و علاقمندی به موضوع، مطلب را برای دیگران نیز بازنشر فرمایید).
📢کانال #دکترامیرمحمدشهسوارانی
🍃🌹🌸💐🌸🌹🍃
@DrAmirMohammadShahsavarani
#Generating testable #hypotheses for #schizophrenia and #rheumatoid arthritis #pathogenesis by integrating #epidemiological, #genomic, and #protein interaction data
پژوهشگران روانپزشکی و اطلاعات بایومدیکال دانشگاه پیتسبورگ 🇺🇸 در پژوهشی که با تازگی منتشر شده است با بررسی های #ژنومی، #همه گیری شناختی، و تعامل #پروتئینی دریافتند که #خطای ژنتیکی منجر به آرتریت رماتوئید و اسکیزوفرنی در نواحی مشابهی از #ژنوم افراد ایجاد می شود.
🔬پیمایش های آمار حیاتی مشخص ساخته اند که در افراد مبتلا به اسکیزوفرنی و خویشاوندان آنها شیوع #رماتوئیدآرتریت به طرز معناداری از جمعیت کلی کمتر است. در پژوهش حاضر آنالیز داده های ژنتیک، به محدوده ای به نام #HLA دست یافت که #ژن های #HLA-B, #TNXB, #NOTCH4, #HLA-C, #HCP5, #MICB, #PSORS1C1, و #C6orf10 در آن قرار دارند. همچنین مشخص شد HLA-B و HLA-C بیشترین دخالت را هم در رماتوئیدآرتریت و هم در اسکیزوفرنی دارند.
Abstract
#Patients with #schizophrenia and their relatives have reduced prevalence of #rheumatoid_arthritis. Schizophrenia and rheumatoid arthritis #genome-wide association studies also indicate negative genetic correlations, suggesting that there may be shared #pathogenesis at the #DNA level or downstream. A portion of the inverse prevalence could be attributed to #pleiotropy, i.e., variants of a single #nucleotide #polymorphism that could confer differential risk for these disorders. To study the basis for such an #interrelationship, we initially compared lists of single nucleotide polymorphisms with significant #genetic associations (p < 1e-8) for schizophrenia or rheumatoid arthritis, evaluating patterns of #linkage #disequilibrium and apparent #pleiotropic risk profiles. Single nucleotide polymorphisms that conferred risk for both schizophrenia and rheumatoid arthritis were localized solely to the extended #HLA region. Among single nucleotide polymorphisms that conferred differential risk for schizophrenia and rheumatoid arthritis, the majority were localized to #HLA-B, #TNXB, #NOTCH4, #HLA-C, #HCP5, #MICB, #PSORS1C1, and #C6orf10; published functional data indicate that HLA-B and HLA-C have the most plausible pathogenic roles in both disorders. #Interactomes of these eight genes were constructed from protein–protein interaction information using publicly available databases and novel #computational #predictions. The genes harboring apparently pleiotropic single nucleotide polymorphisms are closely connected to rheumatoid arthritis and schizophrenia associated genes through common interacting partners. A separate and independent analysis of the interactomes of rheumatoid arthritis and schizophrenia genes showed a significant overlap between the two interactomes and that they share several common pathways, motivating functional studies suggesting a relationship in the #pathogenesis of schizophrenia/rheumatoid arthritis.
لینک منبع 👇🏻(further reading)👇🏻
https://www.nature.com/articles/s41537-017-0010-z
✅(در صورت جذابیت و علاقمندی به موضوع، مطلب را برای دیگران نیز بازنشر فرمایید).
📢کانال #دکترامیرمحمدشهسوارانی
🍃🌹🌸💐🌸🌹🍃
@DrAmirMohammadShahsavarani
npj Schizophrenia
Generating testable hypotheses for schizophrenia and rheumatoid arthritis pathogenesis by integrating epidemiological, genomic…
Researchers in the USA identify variations in eight genes that potentially confer differential risk for schizophrenia and rheumatoid arthritis. Previous studies have shown that patients with schizophrenia (and their relatives) have a reduced risk of developing…