Department of Psychiatry, the University of Texas Southwestern Medical Center, Dallas, TX.
Department of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, GA.
Schizophr Bull. 2021 Jul 8;47(4):1058-1067. doi: 10.1093/schbul/sbab013.
Investigating biomarkers in unaffected relatives (UR) of individuals with psychotic disorders has already proven productive in research on psychosis neurobiology. However, there is considerable heterogeneity among UR based on features linked to psychosis vulnerability. Here, using the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset, we examined cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands, stratified by 2 widely used risk factors: familiality status of the respective proband (the presence or absence of a first- or second-degree relative with a history of psychotic disorder) and age (within or older than the common age range for developing psychosis). We investigated biomarkers that best differentiate the above specific risk subgroups. Additionally, we examined the relationship of biomarkers with Polygenic Risk Scores for Schizophrenia (PRSSCZ) in a subsample of Caucasian probands and healthy controls (HC). Our results demonstrate that the Brief Assessment of Cognition in Schizophrenia (BACS) score, antisaccade error (ASE) factor, and stop-signal task (SST) factor best differentiate UR (n = 169) from HC (n = 137) (P = .013). Biomarker profiles of UR of familial (n = 82) and non-familial (n = 83) probands were not significantly different. Furthermore, ASE and SST factors best differentiated younger UR (age ≤ 30) (n = 59) from older UR (n = 110) and HC from both age groups (age ≤ 30 years, n=49; age > 30 years, n = 88) (P < .001). In addition, BACS (r = -0.175, P = .006) and ASE factor (r = 0.188, P = .006) showed associations with PRSSCZ. Taken together, our findings indicate that cognitive biomarkers-"top-down inhibition" impairments in particular-may be of critical importance as indicators of psychosis vulnerability.
研究未受影响的精神病患者亲属（UR）的生物标志物，已经在精神病神经生物学研究中取得了成果。然而，UR 基于与精神病易感性相关的特征存在相当大的异质性。在这里，我们使用双相-精神分裂症网络中间表型（B-SNIP）数据集，根据两个广泛使用的风险因素：各自先证者的家族性状态（是否存在有精神病病史的一级或二级亲属）和年龄（在或超过精神病发病的常见年龄范围），对精神病先证者的一级 UR 进行认知和神经生理生物标志物研究。我们研究了能够最好地区分上述特定风险亚组的生物标志物。此外，我们在一个白种人先证者和健康对照（HC）的子样本中检查了生物标志物与精神分裂症多基因风险评分（PRSSCZ）的关系。我们的结果表明，简短精神状况检查表（BACS）评分、反扫视错误（ASE）因子和停止信号任务（SST）因子能够最好地区分 UR（n=169）和 HC（n=137）（P=0.013）。家族性（n=82）和非家族性（n=83）先证者 UR 的生物标志物谱没有显著差异。此外，ASE 和 SST 因子能够最好地区分年轻的 UR（年龄≤30 岁）（n=59）与年长的 UR（n=110）和 HC（年龄≤30 岁，n=49；年龄>30 岁，n=88）（P<0.001）。此外，BACS（r=-0.175，P=0.006）和 ASE 因子（r=0.188，P=0.006）与 PRSSCZ 呈关联。总之，我们的研究结果表明，认知生物标志物，特别是“自上而下的抑制”损伤，可能是精神病易感性的重要指标。
