Boudet C, Denise P, Bocca M L, Chabot B, Abadie P, Brazo P, Benali K, Dollfus S
Groupe d'Imagerie Neurofonctionnelle (GIN), UMR 6095 CNRS/CEA/Université de Caen/Université Paris V, Centre Cycéron, boulevard H. Becquerel, 14000 Caen.
Encephale. 2001 Nov-Dec;27(6):551-8.
Several studies have confirmed the existence of genetic factors in schizophrenia. However, the genotype predisposing for the disease is not known yet. Nevertheless, those genetic factors in the families of schizophrenic patients urge us to search for genetic vulnerability markers of schizophrenia. Ocular pursuit disorders, in particular, could be one of those vulnerability markers. Eye movements have been often tested in schizophrenia. Most of the schizophrenic patients have eye-tracking disorders and their biological relatives demonstrate an increased prevalence of eye-tracking impairments. The aim of the study was to research if smooth pursuit eye movements could be a vulnerability marker of schizophrenia. In order to have an indication about this hypothesis, impairments of smooth pursuit eye movements were researched in both schizophrenics and their parents.
Fifteen DSM IV schizophrenic patients stabilized at the time of the inclusion and not treated with lithium, benzodiazepines, barbiturates, or chloral hydrate; 19 parents without history of schizophrenic spectrum disorders (SADSLA and IPDE), and 2 groups of healthy subjects matched in age and sex with probands and with the parents, were included in the study. Parents only were included (fathers or mothers) in order to have an homogeneous population for the genetic risk and age. The eye-tracking paradigm used was a smooth pursuit task. The stimulus was a sinusoidal wave form moving on a horizontal line, with a frequency of 0.4 Hz and an amplitude of 30 degrees. Different parameters were measured: gain (ratio between the eye velocity and the target velocity) and saccades frequencies (catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks). For each parameter, analysis of covariance (ANCOVA) with age as covariable was carried out. For the results reaching the significance of 0.05, the Bonferroni correction was applied (level of significance 0.016). The effect size of the parameter was calculated ((the mean of the subjects minus the mean of the matched controls) divided by standard deviation of the two groups). According to Cohen, 0.20 indicates a small effect size, 0.50 indicates a medium effect size and 0.80 indicates a large effect size.
Comparison between patients and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between patients and their matched controls. The size effects are 0.31 for the global gain, 0.20 for the movements to the left and 0.41 for the movements to the right. The frequencies of total saccades, catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks did not differ significantly between patients and their controls. The size effects for those parameters were 0.09, 0.03, 0.00, 0.39 and 0.63 respectively. Comparison between parents and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between the two groups. The size effects for those parameters were 0.00, 0.05 and 0.17 respectively. The frequency of total saccades did not differ significantly between the groups whereas the size effect was 0.63. The frequency of catch-up saccades was significantly more important in parents than in controls (p = 0.006) and the size effect was 0.80. The other saccadic parameters did not differ significantly between groups, their size effects were 0.24 for the back-up saccades, 0.21 for the anticipatory saccades and 0.00 for the square-wave-jerks. Whereas the gain of the patients had a tendency to be lower than the gain of their controls, no significant difference was observed between patients and their controls. Only a size effect of 0.63 for the frequency of square-wave-jerks was obtained. This large effect size suggests that the difference between patients and controls might be significant in a larger sample. The catch-up saccades frequency between parents and controls was significant. The differences between our study and the previous studies could be due to several factors. The paradigms used were different between the studies and our sample was small (only 15 patients and 19 relatives). Moreover, some patients in the previous studies were treated by lithium, drug well known to modify ocular pursuit and, finally the relatives in the other studies were 10 years older than ours and age is known to alter ocular pursuit. Since an impairment of the smooth pursuit was observed in the relatives of schizophrenic patients but not in the probands, this study does not support the hypothesis that eye-tracking disorders could be considered as a marker of vulnerability of schizophrenia.
多项研究已证实精神分裂症存在遗传因素。然而,导致该疾病的基因型尚不明确。尽管如此,精神分裂症患者家族中的这些遗传因素促使我们去寻找精神分裂症的遗传易感性标记。尤其是眼球追踪障碍可能就是其中一种易感性标记。在精神分裂症研究中,眼动常被检测。大多数精神分裂症患者存在眼动追踪障碍,其生物学亲属的眼动追踪损伤患病率也有所增加。本研究的目的是探究平稳跟踪眼动是否可能是精神分裂症的易感性标记。为了验证这一假设,对精神分裂症患者及其父母的平稳跟踪眼动损伤情况进行了研究。
纳入15例符合《精神疾病诊断与统计手册》第四版(DSM-IV)标准且在纳入时病情稳定、未接受锂盐、苯二氮䓬类药物、巴比妥类药物或水合氯醛治疗的精神分裂症患者;19名无精神分裂症谱系障碍病史(采用情感障碍和精神分裂症检查提纲[SADS-LA]及国际人格障碍检查表[IPDE]评估)的父母,以及两组在年龄和性别上与先证者及父母相匹配的健康受试者。仅纳入父母(父亲或母亲),以便在遗传风险和年龄方面形成同质人群。所采用的眼动追踪范式是一项平稳跟踪任务。刺激物是在水平线上移动的正弦波形,频率为0.4赫兹,振幅为30度。测量了不同参数:增益(眼速度与目标速度之比)和扫视频率(追赶性扫视、反向扫视、预期性扫视和方波急跳)。对于每个参数,以年龄作为协变量进行协方差分析(ANCOVA)。对于达到0.05显著性水平的结果,应用Bonferroni校正(显著性水平为0.016)。计算参数的效应大小((受试者的平均值减去匹配对照组的平均值)除以两组的标准差)。根据科恩的标准,0.20表示小效应大小,0.50表示中等效应大小,0.80表示大效应大小。
患者与匹配对照组的比较:患者与其匹配对照组之间,整体增益、向左运动的增益和向右运动的增益平均值无显著差异。整体增益的效应大小为0.31,向左运动的效应大小为0.20,向右运动的效应大小为0.41。患者与其对照组之间,总扫视、追赶性扫视、反向扫视、预期性扫视和方波急跳的频率无显著差异。这些参数的效应大小分别为0.09、0.03、0.00、0.39和0.63。父母与匹配对照组的比较:两组之间整体增益、向左运动的增益和向右运动的增益平均值无显著差异。这些参数的效应大小分别为0.00、0.05和0.17。两组之间总扫视频率无显著差异,而效应大小为0.63。父母中追赶性扫视的频率显著高于对照组(p = 0.006),效应大小为0.80。其他扫视参数在两组之间无显著差异,反向扫视的效应大小为0.24,预期性扫视的效应大小为0.21,方波急跳的效应大小为0.00。虽然患者的增益有低于其对照组的趋势,但患者与其对照组之间未观察到显著差异。仅方波急跳频率获得了0.63的效应大小。这种大效应大小表明,在更大的样本中患者与对照组之间的差异可能具有显著性。父母与对照组之间追赶性扫视频率存在显著差异。我们的研究与先前研究之间的差异可能归因于几个因素。研究中使用的范式不同,且我们的样本较小(仅15例患者和19名亲属)。此外,先前研究中的一些患者接受了锂盐治疗,锂盐是一种已知会改变眼球追踪的药物,最后,其他研究中的亲属比我们的研究对象大10岁,且已知年龄会改变眼球追踪。由于在精神分裂症患者的亲属中观察到了平稳跟踪损伤,但在先证者中未观察到,本研究不支持眼动追踪障碍可被视为精神分裂症易感性标记的假设。