EARLY ONSET SCHIZOPHRENIA: GENETICS OF UNSTABLE DNA

早发性精神分裂症：不稳定 DNA 的遗传学

• 批准号: 6264410
• 负责人: MARILYN A DAVIES
• 金额: $ 1.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264410
• 关键词: DNA; bipolar depression; blood chemistry; clinical research; disease /disorder etiology; disease /disorder onset; family genetics; genetic susceptibility; human subject; molecular genetics; schizophrenia

Results of family, twin and adoption studies indicate that genetics is of etiological importance in Bipolar Affective Disorder (BPAD). Investigations show that there is considerable family aggregation for bipolar illness. In these studies there is not only an excess of illness in the relatives of probands, but there is increased risk correlated with relatedness. Genetic research has resulted in promising leads for the location of disease-causing alleles. More recent molecular genetic techniques hold promise for discovery of the genetic mechanism(s) for bipolar illness. Recent discoveries of unstable DNA (aberrant expansion of exonic trinucleotide repeats) in the inherited neuropsychiatric disorders of Fragile X syndrome, myotonic dystrophy and Kennedy's disease have generated interest in whether expanding trinucleotide repeat sequences (TNRs) are related to psychiatric disorders, particularly schizophrenia and bipolar illness. This novel mechanism may have relevance because these psychiatric disorders exhibit two features which are common among the neuropsychiatric disorders with unstable DNA: nonmendelian inheritance patterns and genetic anticipation. This research tests the unstable DNA hypothesis of bipolar affective disorder (BPAD). The hypothesis to be tested is that there will be a significant shift toward larger products in probands than controls. A group of 50 probands with early onset bipolar affective disorder (DMS III-R) will be recruited for study. Early onset is defined as demonstrated symptoms of onset of a psychotic illness prior to age 20. All cases for this research study will be reviewed by a psychiatrist who is experienced in psychiatric diagnostic practice. After case review, the proband (and their family if under 18) will be approached for recruitment. Additional information (including sociodemographic, age of first symptoms, age of first treatment, age of first hospitalization, number of hospitalizations, and family history of psychiatric illness will be collected and validated. For DNA extraction 40ml of venous blood will be drawn from each person. DNA obtained from peripheral blood leukocytes of each proband and control will undergo molecular analysis. The GCRC facility will be used as needed for the blood draws.

家庭、双胞胎和收养研究的结果表明，遗传学在双向情感障碍 (BPAD) 中具有重要的病因学意义。调查显示，躁郁症有相当大的家庭聚集性。 在这些研究中，先证者亲属不仅患病过多，而且与亲缘关系相关的风险也增加。遗传学研究为确定致病等位基因的位置提供了有希望的线索。 最近的分子遗传学技术有望发现双相情感障碍的遗传机制。最近在脆性 X 综合征、强直性肌营养不良和肯尼迪病等遗传性神经精神疾病中发现不稳定 DNA（外显子三核苷酸重复序列的异常扩增），引起了人们对扩展三核苷酸重复序列 (TNR) 是否与精神疾病（特别是精神分裂症和双向情感障碍）相关的兴趣。疾病。 这种新机制可能具有相关性，因为这些精神疾病表现出在具有不稳定 DNA 的神经精神疾病中常见的两个特征：非孟德尔遗传模式和遗传预期。这项研究检验了双相情感障碍 (BPAD) 的不稳定 DNA 假说。 要检验的假设是，先证者将比对照组显着转向更大的产品。将招募 50 名患有早发性双相情感障碍 (DMS III-R) 的先证者进行研究。 早发被定义为 20 岁之前出现精神病发作的症状。本研究的所有病例都将由在精神病诊断实践方面经验丰富的精神科医生进行审查。 病例审查后，将联系先证者（及其未满 18 岁的家人）进行招募。 将收集并验证其他信息（包括社会人口统计、首次出现症状的年龄、首次治疗的年龄、首次住院的年龄、住院次数以及精神疾病家族史。为了提取 DNA，将从每个人身上抽取 40 毫升静脉血从每个先证者和对照的外周血白细胞中获得的 DNA 将根据抽血需要进行分子分析。