Transitive inference deficits in unaffected biological relatives of schizophrenia patients.
Transitive inference deficits in unaffected biological relatives of schizophrenia patients.
复制标题
精神分裂症患者未受影响的生物学亲属的传递推理缺陷。
DOI：
10.1016/j.schres.2016.02.015
复制
发表时间：
2016
影响因子：
4.5
通讯作者：
Ho,Beng-Choon
中科院分区：
文献类型：
--
作者：
Onwuameze,ObioraE;Titone,Debra;Ho,Beng-Choon
目前可用的治疗方法在治疗精神分裂症认知障碍方面效果有限。促进认知增强药物发现的努力建议使用各种实验认知范式（包括关系记忆）作为临床药物试验中的评估工具。尽管关系记忆缺陷越来越被认为是精神分裂症的可靠认知标志，但未受影响的生物亲属中的关系记忆表现仍然未知。因此，我们使用先前用于证明精神分裂症相关记忆障碍的经过充分验证的传递推理 (TI) 实验范式评估了 73 名青少年或年轻人（22 名精神分裂症患者的一级亲属和 26 名二级亲属以及 25 名健康对照者 (HC)）。我们发现，TI 缺陷与精神分裂症风险相关，一级亲属比二级亲属表现出更大的损害。在响应 TI 探针对时，一级亲属的 TI 性能较差，精度明显低于 HC，响应时间也较长。二级亲属的反应时间明显快于一级亲属，并且在 TI 表现上与 HC 更相似。我们进一步探讨了 TI 表现与精神分裂症涉及的神经认知领域之间的关系。在 HC 中，反应时间与 FSIQ、言语学习、处理速度、语言能力和工作记忆呈负相关。相比之下，亲属（尤其是一级亲属）的 TI-神经认知关系模式不同，这表明当亲属编码和检索关系记忆时可能会使用不同的大脑回路。我们发现精神分裂症患者未受影响的生物学亲属存在 TI 缺陷，这为在未来的促认知药物研究中使用关系记忆构建提供了进一步的支持。
Currently available treatments have limited efficacy in remediating cognitive impairment in schizophrenia. Efforts to facilitate cognition-enhancing drug discovery recommend the use of varied experimental cognitive paradigms (including relational memory) as assessment tools in clinical drug trials. Although relational memory deficits are increasingly being recognized as a reliable cognitive marker of schizophrenia, relational memory performance among unaffected biological relatives remains unknown. Therefore, we evaluated 73 adolescents or young adults (22 first- and 26 second-degree relatives of schizophrenia patients and 25 healthy controls (HC)) using a well-validated transitive inference (TI) experimental paradigm previously used to demonstrate relational memory impairment in schizophrenia. We found that TI deficits were associated with schizophrenia risk with first-degree relatives showing greater impairment than second-degree relatives. First-degree relatives had poorer TI performance with significantly lower accuracy and longer response times than HC when responding to TI probe pairs. Second-degree relatives had significantly quicker response times than first-degree relatives and were more similar to HC in TI performance. We further explored the relationships between TI performance and neurocognitive domains implicated in schizophrenia. Among HC, response times were inversely correlated with FSIQ, verbal learning, processing speed, linguistic abilities and working memory. In contrast, relatives (first-degree in particular) had a differing pattern of TI-neurocognition relationships, which suggest that different brain circuits may be used when relatives encode and retrieve relational memory. Our finding that unaffected biological relatives of schizophrenia patients have TI deficits lends further support for the use of relational memory construct in future pro-cognition drug studies.