Northwestern University Feinberg School of Medicine, Department of Psychiatry and Behavioral Sciences, 710 N Lake Shore Drive, Chicago, IL, 60611, USA.
Northwestern University Feinberg School of Medicine, Department of Psychiatry and Behavioral Sciences, 710 N Lake Shore Drive, Chicago, IL, 60611, USA.
Schizophr Res. 2020 Jan;215:314-321. doi: 10.1016/j.schres.2019.10.008. Epub 2019 Nov 6.
Eye movement (EM) measures can serve as biomarkers to evaluate pharmacological effects on brain systems involved in cognition. In recent onset schizophrenia, antipsychotic treatment can improve attentional control on the antisaccade task and exacerbate working memory impairment on the memory guided saccade task; effects in treatment-resistant schizophrenia (TRS) are less clear. This study evaluated the effects of high versus low dose lurasidone on EM performance in TRS.
TRS patients completed EM testing: 1) at baseline, on existing medication regimen (n = 42), 2) after 6 weeks of low dose (80 mg) lurasidone (n = 38), 3) after 12 weeks following randomization to low (80 mg) or high dose (240 mg) lurasidone (n = 27), and 4) after 24 weeks of treatment (n = 23). EM testing included prosaccade, antisaccade, and memory guided saccade tasks.
Six weeks of lurasidone resulted in increased prosaccade saccade latency and reduced antisaccade errors, with no change in memory guided saccade accuracy. After randomization, prosaccade and antisaccade latencies increased in only the high dose group, with no change in antisaccade errors in both groups. Memory guided saccade error increased in the high dose group and remained stable in the low dose group.
Among TRS, stabilization on low dose lurasidone was associated with improved executive control of attention reflected by reduced antisaccade errors. High dose lurasidone resulted in prolonged speed of reflexive and executive shifts of attention and reduced spatial working memory relative to low dose. These findings indicate that EM measures are helpful biomarkers of dose-dependent antipsychotic treatment effects on executive cognitive abilities in TRS.
眼球运动（EM）测量可作为生物标志物，用于评估对认知相关脑系统的药物作用。在首发精神分裂症中，抗精神病药物治疗可改善反扫视任务中的注意力控制，并加重记忆引导扫视任务中的工作记忆损伤；但在治疗抵抗性精神分裂症（TRS）中效果不太明确。本研究评估了高低剂量鲁拉西酮对 TRS 患者 EM 表现的影响。
TRS 患者完成 EM 测试：1）在基线时，在现有药物治疗方案下（n=42），2）在接受 6 周低剂量（80mg）鲁拉西酮治疗后（n=38），3）在随机分配至低（80mg）或高（240mg）剂量鲁拉西酮后 12 周（n=27），以及 4）在 24 周治疗后（n=23）。EM 测试包括正性眼跳、反扫视和记忆引导眼跳任务。
6 周的鲁拉西酮治疗导致正性眼跳潜伏期延长和反扫视错误减少，而记忆引导眼跳准确性无变化。随机分组后，仅高剂量组的正性眼跳和反扫视潜伏期增加，两组的反扫视错误均无变化。记忆引导眼跳错误在高剂量组增加，而在低剂量组保持稳定。
在 TRS 中，低剂量鲁拉西酮的稳定与执行控制注意力的改善有关，表现为反扫视错误减少。高剂量鲁拉西酮导致反射性和执行性注意力转移速度延长，以及空间工作记忆减少，与低剂量相比。这些发现表明，EM 测量有助于生物标志物来评估 TRS 中执行认知能力的抗精神病药物治疗剂量依赖性作用。
