Rapoport J L, Giedd J N, Blumenthal J, Hamburger S, Jeffries N, Fernandez T, Nicolson R, Bedwell J, Lenane M, Zijdenbos A, Paus T, Evans A
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md., USA.
Arch Gen Psychiatry. 1999 Jul;56(7):649-54. doi: 10.1001/archpsyc.56.7.649.
Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence.
To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions.
A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups.
Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.
青春期为研究精神分裂症患者大脑区域及特定疾病相关的晚期异常发育提供了一个窗口。由于先前的数据显示，一组儿童期起病的精神分裂症青少年在2年随访期间脑室逐渐增大，而健康对照组无显著变化，我们推测这些患者在青春期其他脑组织的体积会逐渐减小。
为了研究皮质变化，我们对15名儿童期起病的精神分裂症患者（定义为12岁前出现精神病症状）和34名年龄匹配的健康青少年进行了解剖学脑磁共振成像扫描，初始基线扫描时的平均（标准差）年龄为13.17（2.73）岁，随访扫描时为17.46（2.96）岁。使用自动分析系统获取皮质灰质和白质体积，该系统将脑组织分为灰质、白质和脑脊液，并将皮质分为解剖学定义的叶区域。
健康对照组额叶（2.6%）和顶叶（4.1%）区域的皮质灰质体积显著减少。对于儿童期起病的精神分裂症组，这些区域的体积也减少了（分别为10.9%和8.5%），颞叶灰质体积减少了7%。因此，儿童期起病的精神分裂症组表现出独特的疾病特异性模式（变化X区域X诊断的多变量方差分析：F，3.68；P = .004），额叶和颞叶区域的组间差异最大。两组之间白质体积的变化没有显著差异。
极早期起病的精神分裂症患者在青春期皮质灰质体积减少幅度大4倍，且有疾病特异性变化模式。这些患者疾病的病因模型在临床和神经生物学上似乎与晚发性精神分裂症连续，必须同时考虑大脑发育的早期和晚期干扰因素。
