An exploratory study of neurostructural endophenotype among individuals with autistic disorder

自闭症是一种神经发育障碍，其特点是认知能力差，行为和兴趣受到限制和刻板印象，证据表明遗传因素在自闭症的病因中起关键作用。在大约2 / 3的自闭症患者中没有发现自闭症和配偶障碍的家族史。另一方面，神经成像研究表明。在自闭症患者的大脑中不断发现结构异常：在这一点上，结构异常是否与自闭症的家族负荷有关仍有待确定，否则，又是什么。我们研究了1)结构异常是否与自闭症的诊断和自闭症儿童的家族史有关；2)这些异常是否与父亲的出生年龄更大有关。方法选取未接受药物治疗的男性孤独症老年患者（平均年龄2岁，1.2 SD 1.1）和11名健康男性患者（平均年龄22.8 SD 1.6）作为研究对象。诊断是通过半结构化的访谈来确认的。： tic interview-Revised。阳性自闭症家族史的定义是，个体至少有一个一级亲属患有较小的变异（自闭症，由I'给定等人，1997年定义）”，除了lb: Mt：结构异常的参与者外，还通过对至少一个家庭成员的访谈进行了检查，我们对每个参与者进行了AIRIsam。使用统计测图软件（SPM2; hturftwfilion）对图像进行逐体分析。测量的主要指标为脑总体积、脑灰质总体积、脑白质总体积、左右海马体积、小脑总体积，各指标均采用对照组脑总体积的平均值进行标准化。结果14例自闭症患者与11例正常对照组在最大墨迹区未发现体积差异。在14名自闭症患者中，5人的父亲有较少的变异，而对照组中没有发现父亲有更大的变异。然后，我们比较了5名家族性自闭症患者（父亲有较小的变异），9名非家族性自闭症患者，11名对照者的平均兴趣区域体积。在左海马体积上，家族性自闭症个体的均值最高（2.76m1），对照组的均值最低（2.57ml），非家族性自闭症个体的均值最低（2.36ml），两组间差异有统计学意义。14例自闭症个体（32.0岁）的父亲年龄略高于对照组（31.4岁），但两组间差异无统计学意义。结论左海马体积异常可能是家族性/非家族性自闭症的一个指标。少

Background Autism is a neurndevelopmental disorder characterized by poor trial cognition and, by restictod and stereotyped patterns of behavior and interests Evidence suggests that genetic factors play pivotal roles in the aetiology of autistic disorder, whilst. No family history of autistic and Mated disorders can he found in approximately 2 of 3 individuals with autism. On the other hand, nemoimaging studies have suggested that. Structural almonnalities are mnsistently found in brain of individuals with autistic disorder: Tb this point, it remains to be determined whether structuml abnormalities are connected with familial loading to autistic disorder, other-wile, what. Factors, particularly non-genetic litiors (e.g. advanced paternal age at birth), ming for such bruin abnormalities should be expload Objediues We examined 1) whether structural abnormalities rue related to diagnosis of autistic disorder and family history of autistic di: ander and 2) whether such abnormalities me rel … More ated to advanced paternal age at birth. Method Poulton drug-naive male subjects with autistic &senior (mean age 2,1.2 SD 1.1) and 11 healthy male wilutthers (mean age 22.8 SD 1.6) participated in this study. Diagnosis was confirmed using a semi-structured interview, the Autism Di: ann.: tic interview-Revised. Positive family history of autism was defined such that the individual has at least one first-degree relative with lesser variant (of autistic disorder, defined by I'iven, et. Al., 1997)", which was examined through an interview with at least one family member in addition to the participants lb: Mt.: structural abnormalities, we conducted a AIRIsam for each participant. The vosel-wise analyses of images were conducted using statistical pmumetric mapping software (SPM2; hturftwwfilion.uclacads main hi of the measurement were total brain vol tne, total gray matter volume, total white matter volume, left and right hippotnmpal volumes, and total cereballar volume, each of which was standardized using mean value of total brain volume of the control individuals. Results No volume dillerence was found in areas of inkiest between 14 individuals with autisticdisorder and 11 controls. Even alter age WAS adjusted for Among 14 individuals with autistic disorder 5 had the father with lesser variant, whereas no father with hisser variant was found in control group. Thenifine we comparad mean volume of areas of interest among 5 individual with familial autism (having a father with lesser variant), 9 individuals with non-familial autism, 11 control individuals. For left hippommpal volume, individuals with familial autistic disorder indicated the highest mean value (2.76m1), control individuals the Rcond (2.57ml), and the individuals with non-fitmilial autism the lowest (2.36ml), the dillbrence between two groups of autistic disorder being statisticallysignificant Althoughpaternal age wasslightlyhigher in 14 individuals with autism (32.0 yrs) than controls (31.4 yrs), no such difference was found between two groups of autistic disorder. Conslusion Abnormality in left hippocampal volume may be an indicator for familial/non-familial autistic disorder. Less