Bolbecker Amanda R, Kent Jerillyn S, Petersen Isaac T, Klaunig Mallory J, Forsyth Jennifer K, Howell Josselyn M, Westfall Daniel R, O'Donnell Brian F, Hetrick William P
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN;
Larue D. Carter Memorial Hospital, Indianapolis, IN.
Schizophr Bull. 2014 Sep;40(5):1001-10. doi: 10.1093/schbul/sbt112. Epub 2013 Aug 20.
Consistent with reports of cerebellar structural, functional, and neurochemical anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is also present in schizotypal personality disorder, an intermediate phenotype of schizophrenia. The present work sought to determine whether dEBC deficits exist in nonpsychotic first-degree relatives of individuals with schizophrenia. A single-cue tone dEBC paradigm consisting of 10 blocks with 10 trials each (9 paired and 1 unpaired trials) was used to examine the functional integrity of cerebellar circuitry in schizophrenia participants, individuals with a first-degree relative diagnosed with schizophrenia, and healthy controls with no first-degree relatives diagnosed with schizophrenia. The conditioned stimulus (a 400ms tone) coterminated with the unconditioned stimulus (a 50ms air puff to the left eye) on paired trials. One relative and 2 healthy controls were removed from further analysis due to declining conditioned response rates, leaving 18 schizophrenia participants, 17 first-degree relatives, and 16 healthy controls. Electromyographic data were subsequently analyzed using growth curve models in hierarchical linear regression. Acquisition of dEBC conditioned responses was significantly impaired in schizophrenia and first-degree relative groups compared with controls. This finding that cerebellar-mediated associative learning deficits are present in first-degree relatives of individuals with schizophrenia provides evidence that dEBC abnormalities in schizophrenia may not be due to medication or course of illness effects. Instead, the present results are consistent with models of schizophrenia positing cerebellar-cortical circuit abnormalities and suggest that cerebellar abnormalities represent a risk marker for the disorder.
与精神分裂症中小脑结构、功能和神经化学异常的报道一致，在该疾病中已观察到明显的小脑依赖性延迟眨眼条件反射（dEBC）缺陷。dEBC受损也存在于分裂型人格障碍中，这是精神分裂症的一种中间表型。本研究旨在确定精神分裂症患者的非精神病性一级亲属中是否存在dEBC缺陷。采用由10个块组成的单线索音调dEBC范式，每个块有10次试验（9次配对试验和1次非配对试验），以检查精神分裂症患者、有一级亲属被诊断为精神分裂症的个体以及没有一级亲属被诊断为精神分裂症的健康对照者的小脑回路功能完整性。在配对试验中，条件刺激（400毫秒音调）与非条件刺激（向左眼吹气50毫秒）同时终止。由于条件反应率下降，一名亲属和两名健康对照者被排除在进一步分析之外，最终留下18名精神分裂症患者、17名一级亲属和16名健康对照者。随后使用分层线性回归中的生长曲线模型对肌电图数据进行分析。与对照组相比，精神分裂症组和一级亲属组在dEBC条件反应的习得方面明显受损。这一发现表明，精神分裂症患者的一级亲属中存在小脑介导的联想学习缺陷，这为精神分裂症中dEBC异常可能不是由于药物治疗或病程影响提供了证据。相反，目前的结果与精神分裂症模型中假设的小脑 - 皮质回路异常一致，并表明小脑异常是该疾病的一个风险标志物。
