Gavin David P, Sharma Rajiv P
The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, USA.
Cardiovasc Psychiatry Neurol. 2009;2009:409562. doi: 10.1155/2009/409562. Epub 2009 Jul 22.
Background. Studies have implicated abnormalities in epigenetic gene regulation in schizophrenia. Presentation. We hypothesize that identifying abnormalities in chromatin structure and the epigenetic machinery in peripheral blood mononuclear cells (PBMC) from schizophrenia patients could (a) help characterize a subset of schizophrenia patients and (b) lead to targeted pharmacological interventions. Testing. Investigate the relationship between clinical symptoms, demographics, hormonal fluctuations, substance abuse, disease characteristics across the major mental illnesses, and epigenetic parameters in PBMC. In addition, examine the effects of individual antipsychotics, mood stabilizers, as well as experimental agents both as clinically prescribed as well as in cultured PBMC to understand the effects of these agents on chromatin. Implications. If PBMC could serve as a reliable model of overall epigenetic mechanisms then this could lead to a "biomarker" approach to revealing pathological chromatin state in schizophrenia. This approach may provide an informed method for selecting chromatin modifying agents for psychiatric disorders.
背景。研究表明精神分裂症存在表观遗传基因调控异常。
陈述。我们假设,识别精神分裂症患者外周血单个核细胞(PBMC)中的染色质结构和表观遗传机制异常能够(a)帮助刻画一部分精神分裂症患者的特征,以及(b)带来有针对性的药物干预。
测试。研究临床症状、人口统计学特征、激素波动、药物滥用、主要精神疾病的疾病特征与PBMC中的表观遗传参数之间的关系。此外,研究个体抗精神病药物、心境稳定剂以及临床处方用药和培养的PBMC中的实验药物的作用,以了解这些药物对染色质的影响。
意义。如果PBMC能够作为整体表观遗传机制的可靠模型,那么这可能会带来一种“生物标志物”方法,以揭示精神分裂症中病理性染色质状态。这种方法可能为选择用于精神疾病的染色质修饰剂提供一种明智的方法。