Effects of Second-Generation Antipsychotic Medication on Smooth Pursuit Performance in Antipsychotic-Naive Schizophrenia

Abstract

Context Analyses of smooth pursuit eye movement parameters in patients with schizophrenia provide information about the integrity of neural networks mediating motion perception, sensorimotor transformation, and cognitive processes such as prediction. Although pursuit eye tracking deficits have been widely reported in schizophrenia, the integrity of discrete components of pursuit responses and the effect of second-generation antipsychotic medication on them are not well established. Objective To examine different components of smooth pursuit performance in antipsychotic-naive patients with schizophrenia before and after treatment with second-generation antipsychotic medication. Design, Setting, and Participants Thirty-three antipsychotic-naive patients with schizophrenia performed 3 different smooth pursuit paradigms designed to evaluate specific components of the pursuit response. All of the patients were retested after 6 weeks of treatment with risperidone or olanzapine. Testing was also performed with 39 matched healthy individuals. Thirteen patients and 21 healthy participants were retested after 26 and 52 weeks. Main Outcome Measures Pursuit initiation, maintenance gain (ratio of eye velocity over target velocity), and frequency of catch-up saccades during pursuit maintenance. Results Prior to treatment, pursuit gain when tracking less predictable ramp targets tended to be reduced, latency of pursuit initiation was speeded, and catch-up saccade frequency was increased during predictive pursuit. After antipsychotic treatment initiation, pursuit gain decreased with ramp targets, indicating treatment-emergent impairments in sensorimotor processing. No changes were observed for predictive pursuit. Exploratory analyses in the subgroup with follow-up to 1 year revealed that these effects continued through long-term follow-up with some partial normalization at 1 year. Deficits were unrelated to drug dosage and clinical ratings. Conclusions Impaired sensorimotor function was observed after initiation of second-generation antipsychotic medications, which may be explained by their serotonergic antagonism of brainstem sensorimotor systems. Predictive mechanisms supported by frontostriatal-cerebellar circuitry were not affected by treatment initiation and appear able to compensate for treatment-emergent sensorimotor impairments during predictive tracking.

Eye-Head Coordination Abnormalities in Schizophrenia

“…It is well-known that eye-movement parameters are affected by certain drugs, especially those that affect the central nervous system. Benzodiazepines and second-generation antipsychotics can alter eye movements (e.g., generating a decrease in saccadic peak velocity [68], [69]), but they might also affect other eye-movement parameters. Therefore, we have expressed our results regarding medication in terms of CED.…”

Smoking, nicotine and neuropsychiatric disorders

“…Moreover, this impairment is not affected by dopamine D2 receptor antagonist antipsychotics (Tanabe et al, 2006;Thaker, 2007;Lencer et al, 2008), but is also attenuated by NIC administration (by cigarette smoking, NIC patch, or nasal spray) among patients with schizophrenia (Martin and Freedman, 2007). A recent fMRI study by Tanabe et al (2006) showed that NIC improves abnormal SPEM in schizophrenia through modulation of hippocampal and anterior cingulate activity (Tanabe et al, 2006).…”

Eye Tracking Dysfunction in Schizophrenia: Characterization and Pathophysiology

“…6 However, across all studies published since 1993 (which include all open-loop studies and a large subset of closed-loop studies), open-loop pursuit measures have yielded a medium effect size, d of −0.45 (±0.47, n = 12), whereas closed-loop pursuit gain has yielded a large effect size, d , of −0.87 (±0.42, n = 42). For measures of both open- and closed-loop pursuit, deficits have been found even in neuroleptic naïve and unmedicated patients (Hutton et al 1998; Sweeney et al 1998a, 1999; Thaker et al 1999; Lencer et al 2008). These findings suggest that if motion processing deficits contribute to ETD, higher-order processes that would normally compensate for motion processing deficits are affected as well.…”