OBJECTIVE Different cognitive development histories in schizophrenia may reflect variation across dimensions of genetic influence. The authors derived and characterized cognitive development trajectory subgroups within a schizophrenia sample and profiled the subgroups across polygenic scores (PGSs) for schizophrenia, cognition, educational attainment, and attention deficit hyperactivity disorder (ADHD). METHODS Demographic, clinical, and genetic data were collected at the National Institute of Mental Health from 540 schizophrenia patients, 247 unaffected siblings, and 844 control subjects. Cognitive trajectory subgroups were derived through cluster analysis using estimates of premorbid and current IQ. PGSs were generated using standard methods. Associations were tested using general linear models and logistic regression. RESULTS Cluster analyses identified three cognitive trajectory subgroups in the schizophrenia group: preadolescent cognitive impairment (19%), adolescent disruption of cognitive development (44%), and cognitively stable adolescent development (37%). Together, the four PGSs significantly predicted 7.9% of the variance in subgroup membership. Subgroup characteristics converged with genetic patterns. Cognitively stable individuals had the best adult clinical outcomes and differed from control subjects only in schizophrenia PGSs. Those with adolescent disruption of cognitive development showed the most severe symptoms after diagnosis and were cognitively impaired. This subgroup had the highest schizophrenia PGSs and had disadvantageous cognitive PGSs relative to control subjects and cognitively stable individuals. Individuals showing preadolescent impairment in cognitive and academic performance and poor adult outcome exhibited a generalized PGS disadvantage relative to control subjects and were the only subgroup to differ significantly in education and ADHD PGSs. CONCLUSIONS Subgroups derived from patterns of premorbid and current IQ showed different premorbid and clinical characteristics, which converged with broad genetic profiles. Simultaneous analysis of multiple PGSs may contribute to useful clinical stratification in schizophrenia.

中文翻译：

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具有不同认知发展轨迹的精神分裂症亚组的不同多基因评分概况。


目的 精神分裂症的不同认知发展史可能反映了遗传影响各个维度的变化。作者对精神分裂症样本中的认知发展轨迹亚组进行了推导和表征，并对精神分裂症、认知、教育程度和注意力缺陷多动障碍 (ADHD) 的多基因评分 (PGS) 亚组进行了分析。方法 美国国家心理健康研究所收集了 540 名精神分裂症患者、247 名未受影响的兄弟姐妹和 844 名对照受试者的人口统计、临床和遗传数据。认知轨迹亚组是通过使用病前和当前智商估计值进行聚类分析得出的。 PGS 使用标准方法生成。使用一般线性模型和逻辑回归测试关联性。结果聚类分析确定了精神分裂症组中的三个认知轨迹亚组：青春期前认知障碍（19%）、青少年认知发展中断（44%）和青少年认知稳定发展（37%）。四个 PGS 一起显着预测了亚组成员资格的 7.9% 的方差。亚群特征与遗传模式趋同。认知稳定的个体具有最好的成人临床结果，并且仅在精神分裂症 PGS 方面与对照受试者不同。那些患有青少年认知发展障碍的人在诊断后表现出最严重的症状并且存在认知障碍。该亚组的精神分裂症 PGS 最高，并且相对于对照组和认知稳定的个体具有不利的认知 PGS。 与对照组相比，表现出青春期前认知和学业表现受损以及成年结果不佳的个体表现出普遍的 PGS 劣势，并且是唯一在教育和多动症 PGS 方面存在显着差异的亚组。结论 根据病前和当前智商模式得出的亚组表现出不同的病前和临床特征，这些特征与广泛的遗传特征相一致。同时分析多个 PGS 可能有助于精神分裂症的有用临床分层。