Child Psychiatry Branch, National Institute of Mental Health/NIH, 10 Center Drive, Bethesda, MD 20892, USA.
J Am Acad Child Adolesc Psychiatry. 2011 Jul;50(7):697-704. doi: 10.1016/j.jaac.2011.03.016. Epub 2011 Jun 11.
Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to "normalize" by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls.
Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval-matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons.
As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17.
Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings.
儿童期发病的精神分裂症(COS)患者的皮质灰质(GM)异常在青春期进展,最终在成年早期定位于前额叶和颞叶皮质。之前对 52 名 COS 先证者的非精神病性兄弟姐妹进行的一项研究显示,前额叶和颞叶 GM 存在显著缺陷,但到 17 岁时似乎“正常化”。在这里,我们呈现了一组具有非重叠的健康同胞和健康对照组的复制研究。
使用自动测量和前瞻性采集的解剖大脑磁共振图像,我们在非精神病性同胞(n = 43,68 次扫描;年龄 5 至 26 岁)中绘制了 COS 患者的皮质 GM 厚度,将其与年龄、性别和扫描间隔匹配的健康对照组(n = 86,136 次扫描)进行对比。使用虚假发现率程序控制由于多次比较而导致的 I 型错误。
与我们之前的研究一样,年轻的非精神病性同胞(<17 岁)在双侧前额叶和左侧颞叶皮质中表现出显著的 GM 缺陷,此外,在顶叶和右侧颞下回皮质中还存在较小的缺陷。这些非精神病性同胞的缺陷随着年龄的增长而正常化,到 17 岁时仅存在最小的异常。
我们的研究结果支持之前的发现,表明 COS 先证者的非精神病性同胞存在早期 GM 缺陷,随着时间的推移会有所改善。在早期,前额叶和/或颞叶的丧失可能是 COS 的家族/特征标志物。青春期后期似乎是先证者缺陷的最大定位或非精神病性同胞的正常化的关键时期。