Shawn L. Cassady

The Maryland Psychiatric Research Center scale and the characterization of involuntary movements

The Maryland Psychiatric Research Center involuntary movement scale (MPRC scale) has been used in the evaluation of 1107 patients referred for drug-induced movement disorders. The scale has increased discrimination of body area and severity compared to other scales. Validity was examined using principal component analyses, pharmacologic response studies and associations with AIMS, global judgement and motor diagnosis. Reliability was examined using Cronbachs alpha, intraclass correlation coefficient (ICC) between raters and test-retest measurements. The prevalence of dyskinetic and parkinsonian signs at several levels of severity are reported. Total dyskinesia was strongly correlated with AIMS score, r = 0.97. Inter-rater reliability was 0.81-0.90 for total dyskinesia score. Receiver Operating Characteristic (ROC) analysis shows a total dyskinesia score of 4 or above to predict tardive dyskinesia, consistent with RDC-TD criteria. Hand dyskinesia showed a high prevalence comparable to that of oral dyskinesias. The MPRC scale is a valid, sensitive and reliable instrument for the rating of neuroleptic-induced dyskinetic and parkinsonian syndromes and may offer advantages over other scales in neurophysiologic research and brain imaging with its ease of use, uniform structure and greater discrimination of anatomic place and severity in the rating of involuntary movements.

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.

Shifts in covert visual attention in schizophrenic patients and normal controls

Attentional deficits have been consistently demonstrated in schizophrenic patients (Nuecherlein and Dawson 1984). Recently, Posner et al (1988) identified a specific visual attention deficit involving an increased difficulty in shifting covert visual attention, independent of eye movements, when visual attention was invalidly summoned to the left visual field and a target appeared in the right visual field. These investigators also found that the advantage of valid cuing as compared to invalid cuing was less for left visual field targets in schizophrenic patients. However, as the cue served to both alert and spatially orient the subject, their findings may have been due to nonspecific arousal deficits rather than an impaired ability to shift attention. Furthermore, the differences in reaction times in the different cuing conditions may have been due to differences in the perceived brightness or size of the target, as cue and target occurred in close proximity during the valid cuing condition but not in the invalid or uncued condition. Tc examine these alternative possibilities, three modifications were made in the Posner task. First, a 0 msec interval was included as a control

Covert visual attention in schizophrenia spectrum personality disordered subjects: Visuospatial cuing and alerting effects

A recent study observed lateralized deficit in the disengagement of covert visual attention in schizophrenic patients. Subsequent attempts to replicate this finding have had mixed results. Differences in the neuroleptic treatment or other secondary factors associated with schizophrenia are some of the possible reasons for these inconsistent findings. In this study, we examined the ability to shift covert visual attention in neuroleptic-naive, schizophrenia spectrum personality disordered (SSPD; n = 35) subjects and normal controls (n = 34) under a variety of spatial cuing and alerting conditions. We hypothesized that SSPD subjects would have difficulty with disengagement of covert visual attention from an invalidly cued left visual field when the target appeared in the right visual field in comparison to the normal subjects. As predicted, schizophrenia spectrum personality disordered subjects had significantly longer latencies for the right visual field invalid targets than normals (p = .014). Under the remaining cue conditions, spectrum subjects performed normally. Consequently, the cost of left visual field invalid cueing for the right visual field target was significantly higher in spectrum personality subjects than in normals. The cost for the invalid right visual field cue and the benefits of valid cue in both fields were very similar in the two groups. The findings of an asymmetrical deficit in the disengagement and shift of covert visual attention in schizophrenia spectrum subjects are similar to the ones observed in patients with unilateral left hemisphere lesions.

GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia

Saccadic distractibility, Stroop color-word scores, and serial dyskinesia assessments were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol, a potent, direct-acting GABA agonist. Although no significant difference in the measures was evident between conditions, a significant correlation was found between GABA agonist-induced changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo. Improvement in saccadic distractibility was also correlated with reduction in attention performance, as measured by Stroop. These effects are not due to sedation. The correlation between dyskinesia and saccadic distractibility is consistent with a model of parallel motor and oculomotor cortico-striatal-thalamic circuits in humans. This work supports the hypothesis that a dysfunction in GABA-mediated neurotransmission may be the basis for tardive dyskinesia.

Effects of repeated amphetamine administration on antisaccades in schizophrenia spectrum personality

Repeated amphetamine administration is used to examine the responsivity of cerebral dopaminergic systems. Schizophrenia spectrum personality (SSP) provides a unique opportunity to study the pathophysiology of schizophrenia because of shared neurobiology without the confounding factors of acute psychosis and psychotropic exposure. Previously we noted that on repeated amphetamine administration, dyskinesia and SSP symptoms were less likely to worsen in SSP than in healthy volunteers. In the current study, we report the effects of repeated amphetamine on antisaccade task performance. Eleven SSP and seven healthy subjects were given placebo once and amphetamine (30 mg) twice, in randomized double-blind fashion at least 1 week apart. Antisaccade eye measurements (error rate and latency) were recorded over 30 trials in each direction. Analysis of error rate showed no significant main effects of the drug. There was a significant group by field by drug interaction effect on the antisaccade latency. The SSP group showed a significant reduction in antisaccade latency for right field targets whereas no significant effects were noted in healthy control subjects. Findings from this preliminary study suggest SSP may be more receptive to the beneficial effects of repeated amphetamine on cognition than healthy controls.

Negative Symptoms and the Course of Positive Symptoms in Deficit Schizophrenia

Differences in the patterns of negative symptoms between two subgroups of inpatients with chronic schizophrenia and a deficit syndrome were examined: one subgroup presented episodic symptoms, while the other exhibited a continuous course of positive symptoms. Patients with a continuous course of positive symptoms showed significantly higher affective blunting and anhedonia according to the SANS, a lower BPRS activation score and a lower age of onset in males than episodic cases. These results suggest that in deficit schizophrenia different courses of positive symptoms are associated with different severity degrees and different patterns of negative symptoms.