Schizophrenia Predisposition in 22q11 Deletion Syndrome

描述（由研究者提供）：精神分裂症越来越被视为一种神经发育障碍，但由于缺乏同质研究人群，对其病因和病前表现的前瞻性研究受到阻碍。22q11染色体缺失综合征（22q11DS）是一种常染色体显性微缺失综合征，与先天性异常、认知障碍以及青春期后期/成年期精神分裂症和其他主要精神病的发病率显著增加（40%）有关。由于最近才发现22q11DS与精神病之间的关系，因此对这些个体的发病机制和精神病的临床病程知之甚少。我们假设患有22q11DS的非精神病性儿童的一部分将表现出精神分裂症样认知/行为/神经发育缺陷的高发率。理论证据表明，非精神病个体的这种缺陷预示着青春期后期/成年期精神病的高风险。我们建议对35名22q11DS儿童和35名年龄和性别匹配的健康对照进行横断面研究。该研究将通过形态计量学分析评估精神分裂症风险的医疗状况、家谱数据、神经发育历史、智力、心理测量/生物行为/神经认知测量和脑结构异常。我们对13名患有22q11DS的儿童和13名对照组的初步数据表明，患有22q11DS的儿童在持续注意力和执行功能方面表现出更高的缺陷率。在脑MRI上，中线偏差如透明隔空/vergae是常见的（7/13例）。22q11DS患者胼胝体（CC）面积和胼胝体峡部面积增加。在神经心理学和MRI结果的关联上，CC膝的大小增加与言语智商和言语学习记忆的下降有关。因此，我们的研究结果提示22q11DS患儿的神经心理和神经解剖学异常发生率增加。在拟议的横断面研究中进一步描述这些异常，将为未来对这些儿童患精神分裂症和其他精神病风险的纵向研究奠定基础。成功地描述精神分裂症样缺陷应该有助于识别高危个体。该研究的优势在于，我们将检查与特定遗传异常相关的脆弱性，整合各种医学和心理学领域的措施，并确定一个样本，用于发展精神分裂症和相关疾病的风险的纵向研究。

DESCRIPTION (provided by investigator): Schizophrenia is increasingly viewed as a neurodevelopmental disorder, but prospective studies of the etiology and premorbid manifestations are hampered by the lack of a homogeneous study population. Chromosome 22q11 deletion syndrome (22q11DS) is an autosomal dominant microdeletion syndrome, associated with congenital abnormalities, cognitive impairment and a markedly increased incidence (40%) of schizophrenia and other major psychoses in late adolescence/adulthood. Due to the relatively recent discovery of the relationship between 22q11DS and psychosis - there is little knowledge regarding the pathogenesis and the clinical course of psychoses in these individuals. We hypothesize that a subset of nonpsychotic children with 22q11DS will exhibit elevated rates of schizophrenic-like cognitive/behavioral/neurodevelopmental deficits. Theoretical evidence suggests that such deficits in nonpsychotic individuals predict a heightened risk of psychosis in late adolescence/adulthood. We propose a cross-sectional study on 35 children with 22q11DS and 35 age and gender matched healthy control subjects. The study will assess medical status, pedigree data, neurodevelopmental history, intellectual ability, psychometric/biobehavioral/neurocognitive measures of risk for schizophrenia and structural brain abnormalities by morphometric analyses. Our preliminary data on 13 children with 22q11DS and 13 control subjects indicate that children with 22q11DS exhibit higher rates of deficits in sustained attention and executive functioning. On brain MRI, midline deviations such as cavum septum pellucidum/vergae are common (7/13 patients). The corpus callosum (CC) area and the area of the isthmus of the CC are increased in the 22q11DS patients. On correlating the neuropsychological and MRI findings, increasing size of the genu of the CC is associated with decreasing verbal IQ and verbal learning and memory. Thus, our findings are suggestive of increased rates of neuropsychological and neuroanatomical abnormalities in children with 22q11DS. Further characterization of these abnormalities in the proposed cross-sectional study will form the basis of a future longitudinal study of risk for schizophrenia and other psychoses in these children. The successful characterization of schizophrenic-like deficits should facilitate the identification of individuals at high-risk. The strengths of the proposed study are that we would examine vulnerability associated with a specific genetic abnormality, integrate measures from a variety of medical and psychological domains, and ascertain a sample for longitudinal study of risk for developing schizophrenia and related disorders.