Alexander-Bloch Aaron F, Reiss Philip T, Rapoport Judith, McAdams Harry, Giedd Jay N, Bullmore Ed T, Gogtay Nitin
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland; Brain Mapping Unit, Behavioural & Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; David Geffen School of Medicine at UCLA, Los Angeles, California.
New York University School of Medicine, New York, New York; Nathan S. Kline Institute for Psychiatric Research, New York, New York.
Biol Psychiatry. 2014 Sep 15;76(6):438-46. doi: 10.1016/j.biopsych.2014.02.010. Epub 2014 Feb 22.
Schizophrenia is a disorder of brain connectivity and altered neurodevelopmental processes. Cross-sectional case-control studies in different age groups have suggested that deficits in cortical thickness in childhood-onset schizophrenia may normalize over time, suggesting a disorder-related difference in cortical growth trajectories.
We acquired magnetic resonance imaging scans repeated over several years for each subject, in a sample of 106 patients with childhood-onset schizophrenia and 102 age-matched healthy volunteers. Using semiparametric regression, we modeled the effect of schizophrenia on the growth curve of cortical thickness in ~80,000 locations across the cortex, in the age range 8 to 30 years. In addition, we derived normative developmental modules composed of cortical regions with similar maturational trajectories for cortical thickness in typical brain development.
We found abnormal nonlinear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing for the first time between cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia. In addition, we showed that when the brain is divided into five normative developmental modules, the areas with abnormal cortical growth overlap significantly only with the cingulo-fronto-temporal module.
These findings suggest that abnormal cortical development in schizophrenia may be modularized or constrained by the normal community structure of developmental modules of the human brain connectome.
精神分裂症是一种大脑连接紊乱和神经发育过程改变的疾病。不同年龄组的横断面病例对照研究表明，儿童期起病的精神分裂症患者皮质厚度的缺陷可能会随着时间推移而正常化，这表明皮质生长轨迹存在与疾病相关的差异。
我们对106例儿童期起病的精神分裂症患者和102名年龄匹配的健康志愿者进行了多年的磁共振成像扫描。使用半参数回归，我们模拟了精神分裂症对8至30岁年龄段皮质约80,000个位置的皮质厚度生长曲线的影响。此外，我们推导了由典型脑发育中皮质厚度成熟轨迹相似的皮质区域组成的规范性发育模块。
我们发现前额叶和颞叶区域存在异常的非线性生长过程，这些区域先前已被认为与精神分裂症有关，首次区分了皮质厚度存在年龄恒定缺陷的皮质区域和精神分裂症中成熟轨迹改变的区域。此外，我们表明，当将大脑分为五个规范性发育模块时，皮质生长异常的区域仅与扣带回-额叶-颞叶模块有显著重叠。
这些发现表明，精神分裂症中异常的皮质发育可能由人类大脑连接组发育模块的正常群落结构模块化或限制。
