Jay D. Sherr

Effects of Nicotine on Leading Saccades during Smooth Pursuit Eye Movements in Smokers and Nonsmokers with Schizophrenia

Several studies have shown that schizophrenic patients and their biological relatives generate a greater number of leading saccades during smooth pursuit eye movement (SPEM) tasks. This abnormality may reflect a failure of cortical and/or cerebellar areas to coordinate saccadic and pursuit eye movements during visual tracking. The pharmacology of this phenomenon is not known. Here, we sought to replicate and extend the findings of Olincy et al (1998), who found that nicotine transiently reduced the number of leading saccades during SPEMs. A total of 27 subjects with schizophrenia (17 males; 14 smokers), and 25 healthy comparison subjects (nine males; 14 smokers) completed an eye-tracking task after receiving a 1.0 mg nasal spray of nicotine and during drug-free conditions. Results confirm that nicotine reduces the number of leading saccadic eye movements during visual tracking in schizophrenic patients. Baseline impairments and the beneficial effects of nicotine were not restricted to patient smokers, as nonsmoker patients exhibited the greatest number of leading saccades in the no drug condition and exhibited the most pronounced improvements after nicotine administration. Improvement in patient nonsmokers was not a function of previous smoking history. No effect of nicotine was observed in control nonsmokers. In contrast to the previous study, nicotine appeared to improve performance in control smokers. Overall, the study results support a functional role of nACh receptors in improving eye-tracking performance, and are consistent with the hypothesis, articulated by several investigators, that nACh receptor system abnormalities are responsible for a number of schizophrenia-related neurophysiological deficits.

Ethnicity and the course of tardive dyskinesia in outpatients presenting to the motor disorders clinic at the Maryland psychiatric research center.

Background: Although newly emergent tardive dyskinesia (TD) is less of a concern, about one-fourth to one-third of patients on or previously on chronic first-generation antipsychotic agents have TD. The long-term course and outcome, as well as their predictors, are unknown. Earlier studies identify ethnicity as one of the risk factors for the development of TD, and case reports have noted a preponderance of African-American males in cohorts of patients with tardive dystonia. The current study examines the anatomic distribution and course of TD in a cohort of schizophrenia patients of European and African descent with TD who were referred to the Motor Disorders Clinic (MDC). Methods: We evaluated data collected on 1149 TD patients who were given a focused neurologic examination for movement disorders. Movements were evaluated with the MPRC Scale for Involuntary Movements (IMS). All patients met RDC-TD criteria for diagnosis of persistent TD. One to 10-year follow-up data on 528 patients were evaluated to examine the course of TD following recommendations made to referring primary clinicians. Suggested interventions to referring primary clinicians included dose reduction of first-generation antipsychotic medication, or switching to a second-generation antipsychotic. Results: Initial evaluation included 701 European American (EA) patients and 448 African-American (AA) patients. AA patients had a significantly higher proportion of males [χ2(1) = 7.50, P < 0.05]. EA subjects had a higher mean age than AA patients 42.8 ± 11.2 and 39.8 ± 10.4, respectively [F(1,1147) = 22.27, P < 0.05]. Mean neuroleptic exposure (chlorpromazine equivalents) was similar in both groups after controlling for differences in age. Follow-up data analyzed in 528 patients (329 EA and 199AA) showed a significant ethnicity by TD interaction [F(1,504) = 4.26, P < 0.05]. Examination of body distribution of dyskinetic movements showed an effect of ethnicity. Subsequent analyses suggest EA patients experienced more improvement in TD over the course of follow up [F(1,319) = 22.39, P < 0.05] compared with AAs [F(1,189) = 1.58, P > 0.05]. These findings were unchanged when age, change in antipsychotic drug dose, and duration of follow-up were covaried. Conclusion: Reports from earlier studies note ethnicity (African descent) as a risk factor in the development of TD. Our study findings suggest ethnicity might be an important factor in predicting a poor course of TD.