从两个国际队列的治疗耐药精神分裂症中使用克洛札相关的DNA甲基化的纵向变化
Amy L Gillespie1,2, Emma M Walker3, Eilis Hannon3
1Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK. amy.gillespie@psych.ox.ac.uk.
Translational psychiatry
|September 27, 2024
概括
对精神分裂症的克洛扎宾治疗随着时间的推移改变了DNA甲基化和血细胞组成. 这些药物效应可能会混以前关于精神分裂症表观遗传学的研究.
科学领域:
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 克洛扎平是治疗耐药精神分裂症的关键治疗方法.
- 以前的研究将克洛扎与表观遗传变化联系起来,但诊断和药物效应等混因素尚不清楚.
研究的目的:
- 研究克洛扎宾对治疗耐药性精神分裂症谱系障碍患者的DNA甲基化和细胞组成的纵向影响.
- 为了区分药物效应与疾病特异性的表观遗传变化.
主要方法:
- 来自两个独立的患者队伍开始使用克洛扎宾的血DNA甲基化数据的测序分析.
- 利用混合效应回归模型来识别与克洛扎治疗时间相关的差异甲基化位置 (DMP).
- 随着时间的推移,血细胞类型比例的估计变化.
主要成果:
- B细胞比例的显著非线性变化与克洛扎治疗时间有关.
- 鉴定了37个DMP (线性模型) 和90个DMP (非线性模型) 与克洛沙暴露相关.
- 有证据表明,先前确定的精神分裂症相关的DMP可能反映了克洛扎宾的暴露.
结论:
- 克洛扎暴露显著影响DNA甲基化模式和血液细胞组成.
- 药物效应,特别是zapine,可以混神经精神疾病的表观基因组范围的关联研究.
更多相关视频
13:47Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models
Published on: March 29, 2019
9.5K
07:16Rapid and Efficient Spatiotemporal Monitoring of Normal and Aberrant Cytosine Methylation within Intact Zebrafish Embryos
Published on: August 18, 2022
1.4K
相关概念视频
Biological Causes of Schizophrenia
47
Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
47
Epigenetic Regulation
30.9K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
30.9K
Phase II Reactions: Methylation Reactions
150
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
150
Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
507
Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
507
