دورية أكاديمية
Cortical morphological heterogeneity of schizophrenia and its relationship with glutamatergic receptor variations
العنوان: | Cortical morphological heterogeneity of schizophrenia and its relationship with glutamatergic receptor variations |
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المؤلفون: | Xuan Ouyang, Yunzhi Pan, Xudong Chen, Guowei Wu, Yixin Cheng, Wenjian Tan, Manqi Zhang, Mengjie Deng, Zhening Liu, Lena Palaniyappan |
المصدر: | European Psychiatry, Vol 66 (2023) |
بيانات النشر: | Cambridge University Press, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Psychiatry |
مصطلحات موضوعية: | Cortical folding, polymorphisms, prognosis, stratification, unsupervised machine learning, Psychiatry, RC435-571 |
الوصف: | Abstract Background Recent genetic evidence implicates glutamatergic-receptor variations in schizophrenia. Glutamatergic excess during early life in people with schizophrenia may cause excitotoxicity and produce structural deficits in the brain. Cortical thickness and gyrification are reduced in schizophrenia, but only a subgroup of patients exhibits such structural deficits. We delineate the structural variations among unaffected siblings and patients with schizophrenia and study the role of key glutamate-receptor polymorphisms on these variations. Methods Gaussian Mixture Model clustering was applied to the cortical thickness and gyrification data of 114 patients, 112 healthy controls, and 42 unaffected siblings to identify subgroups. The distribution of glutamate-receptor (GRM3, GRIN2A, and GRIA1) and voltage-gated calcium channel (CACNA1C) variations across the MRI-based subgroups was studied. The comparisons in clinical symptoms and cognition between patient subgroups were conducted. Results We observed a “hypogyric,” “impoverished-thickness,” and “supra-normal” subgroups of patients, with higher negative symptom burden and poorer verbal fluency in the hypogyric subgroup and notable functional deterioration in the impoverished-thickness subgroup. Compared to healthy subjects, the hypogyric subgroup had significant GRIN2A and GRM3 variations, the impoverished-thickness subgroup had CACNA1C variations while the supra-normal group had no differences. Conclusions Disrupted gyrification and thickness can be traced to the glutamatergic receptor and voltage-gated calcium channel dysfunction respectively in schizophrenia. This raises the question of whether MRI-based multimetric subtyping may be relevant for clinical trials of agents affecting the glutamatergic system. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 0924-9338 1778-3585 |
Relation: | https://www.cambridge.org/core/product/identifier/S0924933823024082/type/journal_article; https://doaj.org/toc/0924-9338; https://doaj.org/toc/1778-3585 |
DOI: | 10.1192/j.eurpsy.2023.2408 |
URL الوصول: | https://doaj.org/article/189df00071a54e95b04f97f42177f8af |
رقم الأكسشن: | edsdoj.189df00071a54e95b04f97f42177f8af |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 09249338 17783585 |
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DOI: | 10.1192/j.eurpsy.2023.2408 |