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Biomedical subjects

G K Thaker

Publications and source records attributed to G K Thaker.

At least 37 records · Page 2Linked to original sources
PubMed1996

Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients.

OBJECTIVE: The purpose of the current study was to test the specificity of an association between eye tracking abnormality and schizophrenia spectrum personality symptoms in the family members of schizophrenic patients. The studies of biological markers for genetic vulnerability to schizophrenia, which test an association between a biological measure and schizophrenia spectrum personality symptoms, are constrained, since these personality symptoms may lack the specificity for a schizophrenic phenotype. An association between a behavioral measure and these personality symptoms in general can easily be false (i.e., not related to schizophrenic vulnerability). In contrast, a strong deviant finding in the relatives of schizophrenic patients with spectrum personality symptoms, in the presence of a relatively normal finding in spectrum subjects without a known history of schizophrenia, makes the biobehavioral measure an interesting candidate for such investigations. METHOD: Seventy-five subjects recruited from the community who did not have a family history of psychosis completed the study (24 of the 75 had significant schizophrenia spectrum personality symptoms). Thirty-two first-degree relatives of schizophrenic patients (13 with spectrum symptoms) completed the study. Subjects were 18-45 years old and had no DSM-III-R axis I diagnosis. RESULTS: Qualitative smooth pursuit eye movement score was significantly worse in relatives with the spectrum symptoms than in spectrum subjects without a family history of schizophrenia and the nonspectrum relatives. Schizotypal and schizoid symptoms explained a significant amount of the variance in the eye tracking measure in the relatives (31% and 20%, respectively) but not in the community subjects (less than 2%). Relatives of schizophrenic patients with and without the spectrum symptoms had significantly longer antisaccade latency, in spite of comparable latency for visually guided saccades, than the community subjects. CONCLUSIONS: Smooth pursuit abnormality in subjects with schizophrenia spectrum personality disorders is specifically associated with a family history of schizophrenia.

Adolescent↗
PubMed1996

Association of abnormal smooth pursuit eye movements with the deficit syndrome in schizophrenic patients.

OBJECTIVE: The authors' goal was to test the hypothesis that abnormal smooth pursuit eye movements in schizophrenic patients are associated with the deficit syndrome. METHOD: The eye movements of 24 normal comparison subjects, 32 patients with nondeficit schizophrenia, and 11 patients with deficit schizophrenia were tested with infrared oculography using foveapetal step-ramp targets. RESULTS: The group of schizophrenic patients had normal latency to pursuit onset, abnormally decreased open-loop acceleration and abnormally decreased velocity during the periods of closed-loop acceleration and steady-state pursuit. The subgroup of schizophrenic patients with the deficit syndrome had particularly poor performance during the periods of open- and closed-loop acceleration. CONCLUSIONS: Patients with schizophrenia have abnormal smooth pursuit eye movements in response to a step-ramp stimulus, and the defects are particularly pronounced in patients with the deficit syndrome. Abnormal smooth pursuit eye movements in schizophrenia and related disorders have been consistently linked with primary and enduring negative symptoms.

Adult↗
PubMed1995

Abnormal smooth pursuit eye movements in schizophrenic patients are associated with cerebral glucose metabolism in oculomotor regions.

The purpose of this study was to test the hypothesis that abnormal smooth pursuit eye movements in schizophrenic patients would be related to cerebral glucose utilization in specific oculomotor regions. Eye movements were assessed with infrared oculography in 11 unmedicated schizophrenic patients and 13 normal comparison subjects. For the patients only, regional cerebral metabolic rate of glucose utilization was measured with positron emission tomography. Abnormal pursuit tracking in the patients was associated with relatively decreased metabolism in the frontal eye fields and increased metabolism in the caudate nuclei. The results are consistent with the hypothesis that these cerebral regions are involved in the pathophysiology of abnormal pursuit as related parts of a cortical-subcortical oculomotor circuit.

Adult↗
PubMed1994

Psychosis-proneness and verbal memory in a college student population.

Previous research has revealed numerous neuropsychological deficits in schizophrenics. Research on individuals with schizotypal personality features has also demonstrated similar neuropsychological deficits. However, the latter literature is limited in scope. This study examined verbal memory function in psychometrically identified (Chapman Scales) psychosis-prone college students (n = 409). Subjects were administered a standard verbal memory procedure (Logical Memory; Wechsler Memory Scale-Revised) as well as measures of verbal intelligence (Shipley Scale) and depression (Beck Depression Inventory). Results reveal no relationship between degree of schizotypic features and recall measures (immediate recall, delayed recall, and retention rate). Moreover, comparisons between low schizotypic subjects and those scoring at the extreme (greater than 2 standard deviations above the mean) also failed to reveal significant differences in recall. These results raise the possibility that memory deficits may be specific to schizophrenia and not the schizophrenia spectrum or that they are restricted to only those with the familial form of the disorder (i.e., those with family histories of schizophrenia).

Adolescent↗
PubMed1994

Clozapine in tardive dyskinesia: observations from human and animal model studies.

Clozapine has long been considered a useful treatment in patients who have schizophrenia with the neuroleptic-induced delayed-onset side effect tardive dyskinesia. We present data in support of the clinical impression using both an animal model of the disorder and dyskinetic patients themselves. Clozapine produces a lower rate of oral dyskinesia in laboratory rats after 6 months of chronic treatment than does haloperidol (8.6 +/- 1.3 vs. 13.6 +/- 1.4 vacuous chewing movements every 5 minutes, respectively), suggesting a lower propensity to cause tardive dyskinesia. In the human, when clozapine was compared with haloperidol in the treatment of patients with tardive dyskinesia, clozapine produced significantly greater benefit for motor symptoms after 12 months of treatment than did haloperidol (p < .001). Moreover, the dyskinesia rebound, which occurred equally in both drug groups at the beginning of the study, was sustained in the haloperidol group but lost in the clozapine-treated patients. These data suggest that dyskinetic patients lose their symptoms of tardive dyskinesia, along with dopaminergic hypersensitivity, with long-term clozapine treatment.

Adult↗
PubMed1993

Pharmacologic relationship of antisaccade and dyskinesia in schizophrenic patients.

Abnormalities in saccadic eye movements have been found in schizophrenics with tardive dyskinesia (TD). This finding supports accumulating evidence for a GABAergic dysfunction in the subcortical-cortical circuits controlling motor and oculomotor behavior. We found that in response to muscimol, a direct-acting GABA agonist, changes in the antisaccade error rate and dyskinesia score were strongly correlated. We then looked at the relationship between these measures during single-blind haloperidol withdrawal. Significant changes occurred in antisaccade error during drug withdrawal, but the final measure was not significantly different from the baseline assessment. Antisaccade error change scores were not correlated with dyskinesia change scores. Change score in antisaccade error was positively correlated with change on the Brief Psychiatric Rating Scale, specifically with the Anxiety/Depression factor. These findings suggest that GABAergic mechanisms are more robust than dopaminergic mechanisms in the pathophysiology of persistent tardive dyskinesia.

Adult↗
PubMed1992

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.

Adult↗
PubMed1992

Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome.

A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cerebral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.

Adolescent↗
PubMed1991

Tobacco smoking increases square-wave jerks during pursuit eye movements.

Smooth-pursuit eye-movement (SPEM) abnormalities have been consistently observed in schizophrenia. The SPEM changes in schizophrenia are not thought to be an artifact of voluntary attention or medication, although a number of nondisease factors are known to affect SPEM. However, cigarette smoking has recently been reported to deteriorate SPEM in both smokers and nonsmokers. This finding is particularly relevant to schizophrenia, because schizophrenic patients smoke cigarettes considerably more than do normals, and none of the previous studies in this patient group have controlled for smoking. The current study was initiated to examine the effects of smoking on a number of oculomotor measures, including SPEM in smoker and nonsmoker normal volunteers. The results of this study suggest that cigarette smoking induces or significantly increases square-wave jerks, especially during smooth pursuit in normals. However, the effect is small and the global qualitative SPEM score is not affected. Other eye movements such as latencies for reflex and volitional saccades and saccadic distractibility are also unaffected by smoking. No differences were apparent between chronic smokers and nonsmokers under nonsmoking conditions in any of the eye-movement measures.

Adult↗
PubMed1990

Sleep polygraphy in schizophrenia: methodological issues.

The findings of sleep studies in schizophrenia have remained inconsistent in the literature as exemplified by the recent controversy regarding reduced rapid eye movements (REM) latency in these patients. These inconsistencies can partly be explained by major methodological shortcomings in studies evaluating sleep in schizophrenia. Lack of standardized scoring and diagnostic methods in the earlier studies and more recently, the effect of neuroleptic treatment or its withdrawal, have confounded the sleep results. Data are presented to illustrate the effect of the presence of tardive dyskinesia or active psychotic symptoms that further skew the sleep polygraphic measurements in these patients. Studies in drug-naive patients can circumvent some of these confounds but then these studies are weakened by sampling bias. Available data suggest that previous duration of neuroleptic treatment, duration of neuroleptic withdrawal, presence of tardive dyskinesia, and severity of psychotic symptoms should be considered when interpreting REM sleep measures in schizophrenic patients.

Antipsychotic Agents↗
PubMed1990

Clonazepam treatment of tardive dyskinesia: a practical GABAmimetic strategy.

Because of the efficacy of specific gamma-aminobutyric acid (GABA) agonists in tardive dyskinesia, the authors tested the benzodiazepine clonazepam in a 12-week, double-blind, placebo-controlled, randomized crossover trial in 19 chronically ill patients with tardive dyskinesia who were being treated with neuroleptics. They found a 35% decrease in dyskinesia ratings with clonazepam treatment. The six patients with predominantly dystonic symptoms showed greater benefit than the 13 patients with predominantly choreoathetoid dyskinesias. Tolerance developed to the antidyskinetic effect of clonazepam in the five patients whose long-term use of the drug was followed, but a 2-week clonazepam-free period recaptured its antidyskinetic effect.

Adult↗
PubMed1989

Increased saccadic distractibility in tardive dyskinesia: functional evidence for subcortical GABA dysfunction.

In mammals, GABAergic projections from the substantia nigra reticulata to the superior colliculus provide tonic inhibition to tectal neurons involved in the generation of saccades. Dysfunction of this pathway has been shown to produce saccadic "distractibility" in the experimental monkey. In two oculomotor paradigms, control of saccadic eye movements was tested in chronic schizophrenic patients with (n = 18) and without (n = 16) tardive dyskinesia (TD) and normal controls (n = 8). The three groups were matched by mean age; the TD and non-TD patient groups had similar duration of illness, benztropine and chlorpromazine equivalent doses and educational levels. A twofold increase in saccadic distractibility was observed in TD compared to non-TD schizophrenic patients, and both patient groups demonstrated a greater saccadic distractibility than normals. Furthermore, schizophrenic patients (both with and without TD) showed significantly increased latency for "volitional" saccades compared to the normal controls. These findings may provide further evidence for basal ganglia GABA dysfunction in tardive dyskinesia, as well as demonstrate oculomotor abnormalities in schizophrenic individuals.

Adult↗
PubMed1989

Alterations in sleep polygraphy after neuroleptic withdrawal: a putative supersensitive dopaminergic mechanism.

Although a number of studies have reported sleep disturbances following neuroleptic withdrawal, a full description of such changes in sleep architecture is not available. Polysomnographic, plasma prolactin, and clinical measurements were carried out in a small number of patients on chronic neuroleptic treatment and after drug withdrawal. Preliminary findings show that in these chronically treated schizophrenic patients with and without tardive dyskinesia (TD), abrupt neuroleptic withdrawal induces reductions in total sleep, rapid eye movement (REM) sleep, and plasma prolactin. Furthermore, an increase in delta sleep was observed only in patients without TD. The REM suppression occurred significantly earlier in TD patients compared to the non-TD schizophrenic patients. These changes were transient, and both sleep measures and plasma prolactin stabilized during the 2-4 weeks after withdrawal to levels somewhere between the values observed during chronic treatment and withdrawal (week 1) periods. As the withdrawal-induced exaggerated changes mimicked the dopamine agonist effect on these sleep and hormonal measures, one can hypothesize that the observed changes are due to unmasking of supersensitive dopamine receptors following drug cessation. Normalization of these receptors and/or adaptational changes in other nondopaminergic system(s) can hypothetically explain the eventual stabilization of these measures during the following weeks.

Adult↗