Wexler Bruce E, Zhu Hongtu, Bell Morris D, Nicholls Sarah S, Fulbright Robert K, Gore John C, Colibazzi Tiziano, Amat Jose, Bansal Ravi, Peterson Bradley S
Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, 34 Park St., New Haven, CT 06519, USA.
Am J Psychiatry. 2009 Feb;166(2):189-95. doi: 10.1176/appi.ajp.2008.08020258. Epub 2008 Sep 2.
Cognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness.
Patients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N=54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded-stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates.
Both neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects.
Although both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.
认知缺陷在精神分裂症中很突出。患者在广泛的认知测试中的平均得分比正常水平低一个标准差。然而，人们多次注意到，20% - 25%的患者不同于这种一般模式，在神经心理学测试中得分接近正常。本研究采用脑形态测量学来1）识别与更严重认知缺陷相关的脑异常，以及2）帮助确定认知相对完整的患者表现更好是因为他们病情较轻还是因为他们患有不同的疾病。
如果患者在注意力、言语和非言语工作记忆的四项测试中得分在健康对照受试者（N = 30）的0.5个标准差范围内，则被分配到神经心理学接近正常（N = 21）亚组；如果他们的得分比对照受试者至少低1.0个标准差，则被分配到神经心理学受损（N = 54）组。亚组分配通过加利福尼亚言语学习测试和降级刺激连续性能测试得到确认。脑室腔、海马体、杏仁核、丘脑、小脑以及区域皮质灰质和白质的体积为因变量。以性别、年龄和身高作为协变量，使用线性混合模型多变量分析评估组间差异。
神经心理学接近正常和神经心理学受损的患者与健康对照受试者相比，灰质体积明显更小，第三脑室体积更大。然而，只有神经心理学受损的患者与健康对照受试者相比，白质体积明显更小，侧脑室体积更大。
尽管神经心理学受损和神经心理学接近正常的患者在灰质中都有明显的神经病理学改变，但神经心理学接近正常组中相对缺乏白质病理学改变提示疾病过程可能存在差异。
