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Background: Since the prevalence of both sleep-disordered breathing (SDB) and periodic limb movements in sleep (PLMS) increase with age, we explored whether older schizophrenia patients would have a high incidence of SDB and PLMS. Correlations between sleep and clinical variables were also examined. Methods: Fifty-two patients (mean age = 59.6 years, SD = 8.9) had their sleep/wake, respiration, and leg movements recorded using a modified Medilog/Respitrace portable recording system plus oximetry. A battery of clinical, psychosocial, and motor disturbance variables were collected by research center staff. Results: Forty-eight percent of these patients had at least 10 respiratory events per hour of sleep. These patients reported more symptoms of daytime sleepiness than patients with fewer than 10 events per hour. The relatively high prevalence of SDB in this group may contribute to overall sleep disturbances, and does not appear to be a result of high body mass index. Only 14% of the patients had at least five limb movements per hour of sleep, suggesting the prevalence of PLMS is much lower than expected in this age group. The number of leg jerks was inversely related to symptoms of tardive dyskinesia. Conclusions: The disturbance of sleep in these patients may be due, in part, to SDB, but is unlikely due to PLMS.

We evaluated 21 right-handed psychiatric patients with tardive dyskinesia (TD) for the presence and laterality of neuroleptic-induced tremor and rigidity. The goals of the study were to assess the frequency and coexistence of TD and neuroleptic-induced parkinsonism (NIP) using instrumental and clinical measurements and to evaluate the hypothesis that when TD and NIP coexisted in the same patient, they were more likely to appear in opposite limbs. Results indicated that a high percentage of TD patients had coexisting rigidity and tremor on the basis of both clinical ratings and instrumental procedures; however, only instrumental procedures were useful in identifying tremor and rigidity asymmetries. We found that TD and tremor or rigidity did not lateralize to opposite limbs, thus weakening the hypothesis that TD and NIP stemmed from reciprocal pathophysiological mechanisms.

Metoclopramide (MCP) is a D-2 receptor blocker (Kebabian and Calne 1979), which has been available by prescription in the United States since 1979 for use as an antiemetic in a wide range of situations. One of the common indications for MCP is the e Woerner et al1993). There have been case reports but few systematic studies of MCP-associated TD (Sewell et al 1992; Sewell and Jeste 1992; Ganzini et a1 1993). We present hkre preliminary results of a clinical study of MCPassociated TD. We wished to study the frequency of dy&esia in patients with a history of exposure to MCP compared to a non MCP-treated comparison group. We also wished to study localization and course of MCP-associated TD, as well as factors such as the diagnosis of diabetes mellitus which might be associated with an increased risk of TD.

The voluntary motor disturbances found among many schizophrenic patients consist of motor incoordination, disturbed pursuit tracking, difficulty following movement sequences, desynchronized tapping, and a myriad of neurologic soft signs. The problem with many of these observations is that it is extremely difficult to distinguish movement disorders related to neuroleptic treatment from those that may have occurred spontaneously. The aim of the present study was to examine potential disturbances in the voluntary control of steady-state force in neuroleptic-naive schizophrenic patients and normal comparison subjects. Twenty-one patients and 21 age- and gender-matched comparison subjects were studied. Spectral analyses of hand force instability revealed a significant difference between patients and comparison subjects. In 52 of the patients, the disturbance in the control of force exceeded the 95th percentile of the comparison mean. Degree of force instability was correlated with positive but not negative symptoms of schizophrenia. These findings suggest that schizophrenic patients may exhibit a disturbance in the control of muscle force that cannot be attributed to the neuroleptic effects of antipsychotic medication. The pattern of disruption, characterized by abnormal spectral energy within the 1.5 to 3.0 Hz range, suggests a motor disturbance that resembles tardive dyskinesia. Implicit within these findings of neuroleptic naive patients is the possibility that disturbances in the control of isometric force may represent spontaneous dyskinesia.

Most studies suggest that atypical neuroleptics are about equivalent in subjective measures of efficacy, extrapyramidal side effects, and tardive dyskinesia. We are comparing and contrasting the effects of olanzapine 5–20 mg/day and risperidone 2–8 mg/day in outpatients with schizophrenia. Our hypothesis is that risperidone will cause more hand force instability, tremor, and bradykinesia as compared to olanzapine on computerized objective measures because of its greater ex vivo D-2 receptor occupancy. Preliminary analysis (n 5 18 total) shows that the hand force instability prior to study initiation was 6.03 (3.3) for the risperidone group and 6.56 (5.4) for the olanzapine group. The hand force instability after two months of treatment reduced to 4.77 (2.1), 29% and 2.99 (0.9), 57%; respectively (F 5 4.125, p 5 0.05). Hand tremor changed 210.02db to 25.93db with risperidone treatment and 4.35db to 23.03db with olanzapine treatment. Examination of bradykinesia with measures of velocity scaling demonstrates a transition from 2.28 to 2.23 for risperidone treatment vs. 1.54 to 1.67 for olanzapine treatment. These data show that both risperidone and olanzapine improve hyperkinesia and bradykinesia when compared to their status prior to beginning the study. However, olanzapine treatment demonstrated more improvement in hyperkinesia measures, greater decrease in instability and tremor scores, and greater improvement in bradykinesia ie. increased velocity. We will discuss the implications of these data as well as our analysis of the larger 40 patient data set in this presentation.

Studies have demonstrated asymmetric hemispheric dysfunction in patients with schizophrenia and bipolar disorder. However, few studies have compared directly the dysfunction in schizophrenia to that of bipolar disorder, and few have studied hemispheric asymmetries across modalities, which could address regional specificity of lateralized hemispheric dysfunction. We assembled a battery of assessments designed to measure lateralized hemispheric function of the following modalities: sensory information processing and arousal (dichotic listening, chair identification, consonant-vowel-consonant test), memory (Warrington recognition memory test), and motor (hand force instability, velocity scaling, reaction time). To date, 19 right-handed male patients with schizophrenia (N 5 11) and bipolar disorder (N 5 8) have been assessed to determine whether differences in lateralized performance appear across multiple modalities. Effect sizes between diagnostic groups were large for L-R (left minus right) scores for chair identification and velocity scaling and medium for hand force instability. In measures purported to reflect dopaminergic tone (velocity scaling and hand force instability), schizophrenia patients showed diminished right hemispheric function relative to the left, whereas bipolar patients showed diminished left hemispheric function relative to the right. In a measure purported to reflect hemispheric arousal (chair identification), the reverse was true: schizophrenia patients showed diminished left hemispheric function relative to the right, whereas bipolar patients showed diminished right hemispheric function relative to the left. These findings support the literature demonstrating a hemispheric imbalance in schizophrenia and bipolar disorder. They also suggest the possibility that the hemispheric dysfunction in psychosis is complex and may be related to either increased activity in one hemisphere or decreased activity in the other hemisphere. They also indicate that there may exist different mechanisms of hemispheric control, one responsible for motor activity and another for arousal.

Studiesinvestigatingthe biologicalbasis of seasonalaffectivedisorder (SAD)and the mechanismsof actionof light therapyhavefocussedon serotonergicmechanisms.Sofar, the potentialrole of catecholaminergic pathwayshas not been fully explored.We comparedthe effects of tryptophandepletionwiththoseof catecholaminedepletionin a doubleblind, placebo-controlled, balanced, rsndomired crossover study. Patients with SADwhohad respondedto a standardizedregimenof daily 10,OOO-IUX light treatment were included.Tryptopharrdepletionwas induced by ingestion of aminoacidcapsules and a tryptophsn-free sminoacidbeverage,catecholaminedepletionbyingestionofthetyrosine hydroxylaseinhibitor alpha-methyl-para-tyrosine (AMPT).Diphenhydrarnineanda shambeveragewereusedin the placebocondition.Main effectsofconditionandtime,andtheinteractionofconditionx timewere assessedusing 2-wayanalysesof variancewith repeatedmeasures.Of the 16patientsenrolled,3didnotcompletethe study,andtheirdatawere not used for statistical purposes.As predicted, tryptophsndepletion significantlyreducedplasma total and frm tryptophsmconcentrations, catechokurtinedepletion significantlyreduced plasma 3-methoxy-4hydroxyphenylethylenglycol and homovsnillicacid levels.Bothtryptophsmdepletionand catecholaminedepletion,comparedto shamdepletion, induced a transient reoccurrence of depressive symptoms as measuredwith the HamiltonDepressionRatingScale, SeasonalAffective DisorderVersion.The antidepressanteffects oflight therapywere dismptedby both tryptophandepletionand catechokuninedepletion. These tindingssuggestthat brain serotoninand catecholaminesystems maybe involvedin the mechanismof actionof lighttherapy.

We performed a study of the effects of fluphenazine decanoate and antioxidants on head movements striatal cholinergic neurons in rats. Male Sprague-Dawley rats (aged 13 months) received 10 mg/kg fluphenazine decanoate or sesame seed oil IM q 2 weeks for 4 months. The animals were divided into four groups, with sesame oil or fluphenazine injections and basal or antioxidant diet (with supplemented vitamin E, C, and betacarotene). At baseline and after treatment, head movements were quantified by accelerometry. Striatal cholinergic neurons were quantified by counting ChAT-stained cells using the disector technique. The results of the quantitative motor testing revealed a significant main effect for diet (F 13.01, df(1,25), p < 0.002) and for treatment (F = 4.3, dr(1,25), p < 0.05). The results of the cholinergic neuron analysis revealed a significant main effect for diet (F 20.1, df(1,28), p < 0.0002) and for treatment (F ~ 9.0, df(l,28), p < 0.006). There was a significant correlation (r = -0.50, p < 0.01 ) between the motor change scores and the density of cholinergic neurons in the striatum. Our findings suggest that (1) long-term neuroleptic treatment causes a reduction in striatal cholinergic neurons and an increase in head movements, (2) the increase in head movements relates to the density of cholinergic neurons, and (3) these abnormalities are reduced by antioxidants. The increase in head movements observed in rats treated long-term with neuroleptic drugs suggests that this technique has potential to serve as an animal model for TD.

This paper reports the results of an investigation of voluntary control of lip, jaw, and tongue movements in schizophrenic patients with and without tardive dyskinesia. The aims of the study were to determine if voluntary orofacial motor control is disrupted in schizophrenia and to evaluate the relationship between voluntary motor control deficits and selected neurological and behavioral variables. Twenty-two schizophrenic patients and 13 normal control subjects were studied. Of the patients, 11 had moderate to severe TD. Analyses were made of performance on pursuit tracking tasks to evaluate differences between TD and non-TD patients and between medicated and currently unmedicated patients. The results indicated significant group differences in voluntary orofacial motor control. The finding that many non-TD patients exhibited voluntary motor dyscontrol suggests that this may represent a disorder independent of the involuntary dyskinesia. The findings indicated that the level of neuroleptic and/or antiparkinsonian medication was unrelated to the degree of voluntary motor control impairment. The results are discussed in terms of probable neurophysiological mechanisms underlying the motor control deficits in schizophrenia.