Arnold Sara J M, Ivleva Elena I, Gopal Tejas A, Reddy Anil P, Jeon-Slaughter Haekyung, Sacco Carolyn B, Francis Alan N, Tandon Neeraj, Bidesi Anup S, Witte Bradley, Poudyal Gaurav, Pearlson Godfrey D, Sweeney John A, Clementz Brett A, Keshavan Matcheri S, Tamminga Carol A
Department of Psychiatry, UT Southwestern Medical Center, 5352 Harry Hines Boulevard, NE5.110H, Dallas, TX 75235;
Department of Psychiatry, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA;
Schizophr Bull. 2015 Jan;41(1):233-49. doi: 10.1093/schbul/sbu009. Epub 2014 Feb 20.
This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3 Proc MIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007-.02) and SAD (P = .003-.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18-.55). All relative groups had hippocampal volumes not different from controls (P = .12-.97) and higher than those observed in probands (P = .003-.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64-.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51-.73, P < .05). These findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness.
本研究在双相情感障碍 - 精神分裂症中间表型网络（B - SNIP）的精神病样本中，将海马体体积作为精神病性疾病的一种假定生物标志物进行了研究，对比了手动追踪和半自动（FreeSurfer）感兴趣区域的结果。研究样本（n = 596）包括精神分裂症患者（SZ，n = 71）、分裂情感性障碍患者（SAD，n = 70）和精神病性双相I型障碍患者（BDP，n = 86）；他们的一级亲属（SZ - Rel，n = 74；SAD - Rel，n = 62；BDP - Rel，n = 88）；以及健康对照者（HC，n = 145）。海马体体积通过使用手动追踪/3DSlicer3.6.3和半自动分割/FreeSurfer5.1（64位）从3特斯拉T1加权MPRAGE图像中得出。使用混合效应回归模型（SAS9.3 Proc MIXED），在HC以及3种诊断的患者及其亲属中对比了两种方法的体积测量结果；计算了手动追踪和FreeSurfer结果之间的Pearson相关性。与HC相比，SZ（P = .0007 - .02）和SAD（P = .003 - .14）的海马体体积较小，而BDP双侧体积正常（P = .18 - .55）。除了双相情感障碍患者与亲属之间的FreeSurfer测量结果（P = .64 - .99）外，所有亲属组的海马体体积与对照组无差异（P = .12 - .97）且高于患者组（P = .003 - .09）。手动追踪和FreeSurfer的结果显示出直接的、中度到高度的相关性（r = .51 - .73，P < .05）。来自大量精神病样本的这些发现支持海马体体积减小作为精神分裂症和分裂情感性障碍的一种假定生物标志物，但不支持作为精神病性双相I型障碍的生物标志物，这可能反映了不同原发性疾病过程和/或终生用药的累积效应。手动追踪和半自动分割区域体积测量方法可能为定义严重精神疾病潜在的可测量生物标志物提供有用的结果。
