Roalf David R, Vandekar Simon N, Almasy Laura, Ruparel Kosha, Satterthwaite Theodore D, Elliott Mark A, Podell Jamie, Gallagher Sean, Jackson Chad T, Prasad Konasale, Wood Joel, Pogue-Geile Michael F, Nimgaonkar Vishwajit L, Gur Ruben C, Gur Raquel E
Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Biol Psychiatry. 2015 Jan 15;77(2):137-46. doi: 10.1016/j.biopsych.2014.05.009. Epub 2014 May 28.
Brain abnormalities of subcortical and limbic nuclei are common in patients with schizophrenia, and variation in these structures is considered a putative endophenotype for the disorder. Multiplex-multigenerational families with schizophrenia provide an opportunity to investigate the impact of shared genetic ancestry, but these families have not been previously examined to study structural brain abnormalities. We estimate the heritability of subcortical and hippocampal brain volumes in multiplex-multigenerational families and the heritability of subregions using advanced shape analysis.
The study comprised 439 participants from two sites who underwent 3T structural magnetic resonance imaging. The participants included 190 European-Americans from 32 multiplex-multigenerational families with schizophrenia and 249 healthy comparison subjects. Subcortical and hippocampal volume and shape were measured in 14 brain structures. Heritability was estimated for volume and shape.
Volume and shape were heritable in families. Estimates of heritability in subcortical and limbic volumes ranged from .45 in the right hippocampus to .84 in the left putamen. The shape of these structures was heritable (range, .40-.49), and specific subregional shape estimates of heritability tended to exceed heritability estimates of volume alone.
These results demonstrate that volume and shape of subcortical and limbic brain structures are potential endophenotypic markers in schizophrenia. The specificity obtained using shape analysis may improve selection of imaging phenotypes that better reflect the underlying neurobiology. Our findings can aid in the identification of specific genetic targets that affect brain structure and function in schizophrenia.
皮层下和边缘核的脑结构异常在精神分裂症患者中很常见，这些结构的变异被认为是该疾病的一种假定内表型。患有精神分裂症的多重多代家庭为研究共同遗传血统的影响提供了机会，但此前尚未对这些家庭进行研究以探讨脑结构异常情况。我们使用先进的形状分析方法，估计多重多代家庭中皮层下和海马脑容量的遗传度以及亚区域的遗传度。
该研究包括来自两个地点的439名参与者，他们接受了3T结构磁共振成像检查。参与者包括来自32个患有精神分裂症的多重多代家庭的190名欧裔美国人以及249名健康对照受试者。在14个脑结构中测量了皮层下和海马的体积及形状。估计了体积和形状的遗传度。
家庭中的体积和形状具有遗传性。皮层下和边缘体积的遗传度估计值范围从右侧海马的0.45到左侧壳核的0.84。这些结构的形状具有遗传性（范围为0.40 - 0.49），并且特定亚区域形状的遗传度估计值往往超过仅体积的遗传度估计值。
这些结果表明，皮层下和边缘脑结构的体积和形状是精神分裂症潜在的内表型标志物。使用形状分析获得的特异性可能会改善对成像表型的选择，从而更好地反映潜在的神经生物学特性。我们的研究结果有助于识别影响精神分裂症脑结构和功能的特定基因靶点。
