Sherr Jay D, Myers Carol, Avila Matthew T, Elliott Amie, Blaxton Teresa A, Thaker Gunvant K
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Catonsville, USA.
Biol Psychiatry. 2002 Oct 1;52(7):721-8. doi: 10.1016/s0006-3223(02)01342-2.
The role of neuronal nicotinic receptors in the etiology and pathophysiology of schizophrenia has been suggested by postmortem findings as well as by linkage analysis implicating chromosome 15q14, the region where the alpha-7 nicotinic receptor gene is located. In addition, drug probe studies show that acute nicotine administration reverses sensory gating and eye-tracking deficits associated with the genetic liability for schizophrenia. The purpose of the current study was to examine the effects of acute administration of nicotine on specific measures of smooth pursuit eye movements and visual attention.
Twenty nine subjects with schizophrenia (15 smokers and 14 nonsmokers), and 26 healthy comparison subjects (15 smokers and 11 nonsmokers) completed testing. The effects of 1 mg of nicotine, administered by nasal spray, on smooth pursuit initiation, pursuit maintenance, and predictive pursuit were examined.
Nicotine significantly improved eye acceleration during smooth pursuit initiation in both smoker and nonsmoker patients but had no effects in healthy subjects. The fact that patient initiation eye acceleration in response to nicotine was significantly higher than in healthy subjects suggests that the lack of effect in healthy subjects was not due to ceiling effects. Nicotine significantly improved pursuit gain during maintenance at a target velocity of 18.7 deg/sec. There were no effects of nicotine on visually guided and memory saccades, or visual attention (d' from a continuous performance task).
Nicotine showed differential effects in schizophrenic patients compared to healthy subjects. These effects of nicotine were unlikely the result of differences in vigilance or sustained attention, because saccadic peak velocity, a sensitive measure of vigilance, and continuous performance task measures were not affected by nicotine. These findings are not thought to be an artifact of nicotine withdrawal effects at baseline, because the abstinence period was very short, and there were similar effects of nicotine on initiation in nonsmoker patients. These findings suggest an abnormality in neuronal nicotinic system functioning in schizophrenic patients.
尸检结果以及涉及15q14染色体（α-7烟碱型受体基因所在区域）的连锁分析表明，神经元烟碱型受体在精神分裂症的病因学和病理生理学中发挥作用。此外，药物探针研究表明，急性给予尼古丁可逆转与精神分裂症遗传易感性相关的感觉门控和眼球追踪缺陷。本研究的目的是检验急性给予尼古丁对平稳跟踪眼球运动和视觉注意力特定指标的影响。
29名精神分裂症患者（15名吸烟者和14名非吸烟者）以及26名健康对照者（15名吸烟者和11名非吸烟者）完成了测试。通过鼻喷雾剂给予1毫克尼古丁，检测其对平稳跟踪启动、跟踪维持和预测性跟踪的影响。
尼古丁显著改善了吸烟者和非吸烟者患者在平稳跟踪启动期间的眼球加速度，但对健康受试者没有影响。患者对尼古丁产生的启动眼球加速度显著高于健康受试者，这表明健康受试者中未出现影响并非由于天花板效应。在目标速度为18.7度/秒的维持过程中，尼古丁显著改善了跟踪增益。尼古丁对视觉引导和记忆性扫视或视觉注意力（连续操作任务中的d'值）没有影响。
与健康受试者相比，尼古丁在精神分裂症患者中表现出不同的效应。尼古丁的这些效应不太可能是警觉性或持续注意力差异的结果，因为扫视峰值速度（一种敏感的警觉性指标）和连续操作任务指标不受尼古丁影响。这些发现不被认为是基线时尼古丁戒断效应的假象，因为戒断期非常短，且尼古丁对非吸烟者患者的启动也有类似影响。这些发现表明精神分裂症患者的神经元烟碱系统功能存在异常。
