Abstract
Background: 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 α-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.
Methods: 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.
Results: 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).
Conclusions: 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.
Keywords
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References
- Neuronal correlates of inferred motion in primate posterior parietal cortex.Nature. 1995; 373: 518-521
- The mechanism of prediction in human smooth pursuit eye movements.J Physiol. 1991; 439: 439-461
- Ocular pursuit responses to repeated, single-cycle sinusoids reveal behavior compatible with predictive pursuit.J Neurophysiol. 2000; 84: 2340-2355
- Functional MRI of lateral occipitotemporal cortex during pursuit and motion perception.Ann Neurol. 1996; 40: 387-398
- Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia.Neuropsychopharmacology. 2000; 23: 351-364
- Impaired attention, genetics, and the pathophysiology of schizophrenia [published erratum appears in Schizophr Bull 1994;20:248].Schizophr Bull. 1994; 20: 31-46
- Effects of diazepam and buspirone on reaction time of saccadic eye movements.Neuropsychobiology. 1995; 32: 156-160
- Measuring nicotine dependence.J Behav Med. 1989; 12: 159-182
- Desensitization of nicotinic receptors in the central nervous system.Ann N Y Acad Sci. 1999; 868: 620-623
- The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia.J Chem Neuroanat. 2000; 20: 299-306
- Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia.Biol Psychiatry. 1995; 38: 22-33
- Social Class and Mental Illness. John Willey & Sons, New York1988
- Pursuit eye movement dysfunctions in schizophrenia. Family evidence for specificity.Arch Gen Psychiatry. 1984; 41: 136-139
- On the influence of smoking upon smooth pursuit eye movements of schizophrenics and normal controls.J Psychophysiol. 1991; 5: 361-369
- Modulation of pursuit eye movements by stimulation of cortical areas MT and MST.J Neurophysiol. 1989; 62: 31-47
- Smoking and schizophrenia.Eur J Pharmacol. 2000; 393: 237-242
- Visual motion processing and sensory-motor integration for smooth pursuit eye movements.Annu Rev Neurosci. 1987; 10: 97-129
- Visual motion analysis for pursuit eye movements in area MT of macaque monkeys.J Neurosci. 1999; 19: 2224-2246
- Smooth-pursuit eye movement representation in the primate frontal eye field.Cereb Cortex. 1991; 1: 95-102
- Deficits in visual motion processing following ibotenic acid lesions of the middle temporal visual area of the macaque monkey.J Neurosci. 1985; 5: 825-840
- Relation of cortical areas MT and MST to pursuit eye movements. II. Differentiation of retinal from extraretinal inputs.J Neurophysiol. 1988; 60: 604-620
- Improvement in smooth pursuit eye movements after cigarette smoking in schizophrenic patients.Neuropsychopharmacology. 1998; 18: 175-185
- Reliability of the Fagerstrom Tolerance Questionnaire and the Fagerstrom Test for Nicotine Dependence.Addict Behav. 1994; 19: 33-39
- Smooth pursuit eye movements in parents of schizophrenic probands.Schizophr Res. 1997; 24: 244-245
- Eye movements in spectrum personality disorders.Am J Psychiatry. 1996; 153: 362-368
- Tobacco smoking increases square-wave jerks during pursuit eye movements.Biol Psychiatry. 1991; 29: 82-88
- Smooth pursuit eye movements to extraretinal motion signals.Psychiatry Res. 1999; 88: 209-219
- Smooth pursuit eye movements to extraretinal motion signals.Arch Gen Psychiatry. 1998; 55: 830-836
- Saccadic eye movement abnormalities in relatives of patients with schizophrenia.Schizophrenia Res. 2000; 45: 235-244
- Functional analysis of human MT and related visual cortical areas using magnetic resonance imaging.J Neurosci. 1995; 15: 3215-3230
- Human smooth pursuit during transient perturbations of predictable and unpredictable target movement.Exp Brain Res. 1988; 72: 95-108
- Ketamine effects on eye movements.Neuropsychopharmacology. 2000; 23: 645-653
Article info
Publication history
Accepted:
January 25,
2002
Received in revised form:
January 8,
2002
Received:
September 28,
2001
Identification
Copyright
© 2002 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
