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精神分裂症先证者的年轻生物学亲属的海马体积缺陷和形状畸形。

Hippocampal volume deficits and shape deformities in young biological relatives of schizophrenia probands.

机构信息

Department of Psychiatry, W278 GH, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

出版信息

Neuroimage. 2010 Feb 15;49(4):3385-93. doi: 10.1016/j.neuroimage.2009.11.033. Epub 2009 Nov 23.

Abstract

Hippocampal volume decrement may be one of the changes that most closely pre-date schizophrenia onset. Studying hippocampal developmental morphology in adolescent or young adult biological relatives of schizophrenia probands has the potential to further our understanding of the neurodevelopmental etiology of schizophrenia and to discover biomarkers that may aid its early identification. We utilized an artificial neural network segmentation algorithm to automatically define and reliably measure MRI hippocampus volumes. We compared 46 young, nonpsychotic biological relatives of probands against 46 healthy controls without family history of schizophrenia and 46 schizophrenia probands (age range=13 to 28 years). We further contrasted hippocampal shape differences using spherical harmonic functions and assessed how obstetric complications (a trigger for aberrant in utero neurodevelopment) may contribute to hippocampal abnormalities. Similar to schizophrenia probands, unaffected biological relatives of probands had significantly smaller hippocampus volumes than controls; which correspond to inward displacements in shape deformities principally in the anterior hippocampal subregions. Examination of hippocampus volume-age relationships indicate that hippocampus volume normally decreases with age during late adolescence through early adulthood. In contrast, relatives of probands did not show these age-expected changes. Deviant hippocampus volume-age relationships suggest aberrant hippocampal neurodevelopment among biological relatives. Relatives with a history of obstetric complications had significantly smaller left and right hippocampi than relatives without obstetrics complications, including a dose relationship such that greater number of birth complications correlated with smaller hippocampus. Similar hippocampal volume deficits-obstetric complications relationships were observed among schizophrenia probands. Hippocampal abnormalities in schizophrenia are likely to be mediated by different neurobiological mechanisms, including factors associated with obstetric complications which occur during early neurodevelopment. Other brain maturational anomalies affecting the hippocampus in schizophrenia may manifest closer to illness onset in adolescence/early adulthood.

摘要

海马体积减少可能是最早出现精神分裂症前的变化之一。研究精神分裂症患者的青少年或年轻成年生物亲属的海马发育形态,有可能进一步了解精神分裂症的神经发育病因,并发现有助于早期识别的生物标志物。我们使用人工神经网络分割算法自动定义和可靠地测量 MRI 海马体体积。我们将 46 名年轻、非精神病的精神分裂症患者的生物学亲属与 46 名无精神分裂症家族史的健康对照者和 46 名精神分裂症患者(年龄范围为 13 至 28 岁)进行了比较。我们进一步使用球谐函数对比了海马形状差异,并评估了产科并发症(导致宫内神经发育异常的诱因)如何导致海马异常。与精神分裂症患者相似,未受影响的精神分裂症患者的生物学亲属的海马体体积明显小于对照组;这对应于形状变形中的向内位移,主要在前海马亚区。检查海马体体积与年龄的关系表明,在青春期晚期至成年早期,海马体体积通常会随着年龄的增长而减少。相比之下,患者亲属没有表现出这些与年龄相关的变化。异常的海马体体积与年龄的关系表明,患者亲属的海马体神经发育异常。有产科并发症史的亲属的左右海马体明显小于没有产科并发症的亲属,包括剂量关系,即出生并发症越多,海马体越小。在精神分裂症患者中也观察到了类似的海马体体积缺陷-产科并发症关系。精神分裂症中的海马体异常可能是由不同的神经生物学机制介导的,包括与早期神经发育期间发生的产科并发症相关的因素。影响精神分裂症中海马体的其他大脑成熟异常可能在青少年/成年早期更接近发病时表现出来。

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