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Gunvant K Thaker

Publications and source records attributed to Gunvant K Thaker.

36 records · Page 2Linked to original sources
PubMed2004

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 [chi(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.

Adult↗
PubMed2004

Catechol O-methyltransferase polymorphism and eye tracking in schizophrenia: a preliminary report.

OBJECTIVE: This study examined associations between functional polymorphism (Val(108/158) Met) in the catechol O-methyltransferase (COMT) gene and eye tracking measures in schizophrenia. METHOD: Predictive pursuit and closed-loop gains of 62 patients with schizophrenia and 53 healthy comparison subjects with Val-Val, Val-Met, and Met-Met genotypes were compared. RESULTS: There was a significant diagnosis-by-genotype interaction: patients with the Met-Met genotype showed poor predictive pursuit. The Met-Met genotype in healthy subjects was associated with significantly higher predictive pursuit gain values than the Val-Val genotype in healthy subjects. The COMT genotype explained about 10% of the variance in each group's predictive pursuit performance. DISCUSSION: These preliminary data suggest that the COMT gene is associated with predictive eye tracking performance in healthy subjects. Predictive pursuit abnormality in schizophrenia is not attributable to the Val allele. These findings suggest a complex interaction with other etiological factors (e.g., another gene), and/or with prefrontal cortical dopaminergic activity.

Adult↗
PubMed2003

Components of the smooth pursuit function in deficit and nondeficit schizophrenia.

The diagnosis of schizophrenia likely encompasses a heterogeneous group of disorders, complicating the search for its causes. Studies of deficit schizophrenia represent an attempt to reduce this heterogeneity by identifying biologically distinct subgroups. Supplementing clinical phenotypes with biological markers of risk (e.g., eye-tracking and sensory-gating deficits) have also been used to reduce disease heterogeneity. In this study, we examined smooth pursuit eye movements in healthy controls (n = 37), and deficit (n = 18) and nondeficit (n = 32) patients with schizophrenia to determine what aspects of abnormal smooth pursuit are associated with the two patient groups, and which, if any, specifically mark the deficit phenotype. A small sample of relatives of deficit (n = 12) and nondeficit (n = 35) patients was also examined. Positive symptoms were equally present in deficit and nondeficit patients. Subtle, psychotic-like positive traits were also equally present in the relatives of both deficit and nondeficit probands, whereas negative symptoms were significantly more prevalent among the relatives of deficit probands. Deficits in predictive pursuit were present in both patient groups and both groups of relatives. Deficit patients showed significantly lower initiation acceleration. A similar pattern of results was seen in our pilot sample of relatives of deficit patients. These findings suggest that predictive smooth pursuit abnormality is associated with positive symptoms in schizophrenia, and that initiation abnormalities may be associated with the deficit syndrome.

Adult↗
PubMed2003

Association between Val108/158 Met polymorphism of the COMT gene and schizophrenia.

Schizophrenia is a complex disorder with a multifactorial polygenic inheritance with several genes conferring susceptibility at many genetic locations, each with a small effect. An attractive candidate gene for schizophrenia is the catechol-O-methyltransferase (COMT) gene, which is a modulator of dorsolateral prefrontal cortical function. A missense G to A mutation in this gene that results in a substitution of Methionine (Met) for Valine (Val) at codon 108/158 (Val(108/158) Met) has recently been identified in association to schizophrenia. We compared allele frequencies of the variant Val allele between 96 schizophrenia cases and 80 normal controls. We selected controls from a similar pool to cases in ethnicity and gender. The frequency of the Val allele was significantly higher in schizophrenia cases compared to controls (0.620 vs. 0.506; P = 0.043). Calculation of the population attributable risk suggests that the Val allele accounts for as much as 23% of schizophrenia in this population (range: 3-38%). These results provide support for a role of this variant in the etiopathophysiology of schizophrenia.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

Using neurophysiological markers of genetic risk to define the boundaries of the schizophrenia spectrum phenotype.

There is considerable evidence that schizophrenia spectrum personality (SSP) disorders mark genetic risk for schizophrenia. Use of the spectrum phenotype in genetic and neurophysiological studies may prove informative. However, the degree to which the current diagnostic criteria correspond with genetic risk is unclear. This can be assessed by observing how measures of liability among SSP subjects change as a function of diagnostic criteria. In this study the generalized estimating equation method was used to assess changes in eye-tracking performance among SSP and non-SSP family and community groups employing various diagnostic criteria. Eye-tracking deficits among SSP relatives remained statistically higher compared with the other groups across progressively more liberal SSP criteria. The results suggest that fewer traits than are used in clinical diagnoses can effectively identify the spectrum phenotype among relatives of schizophrenia patients. Thus, reduced criteria may be used in research to increase "high risk" sample size and power to detect neurophysiological and genetic differences. Our results provide suggestive evidence that the use of clinical criteria in research may, in fact, underidentify at-risk individuals--potentially distorting genetic and neurophysiological findings.

Adult↗
PubMed2003

Neurodevelopmental interactions conferring risk for schizophrenia: a study of dermatoglyphic markers in patients and relatives.

Schizophrenia is hypothesized to be the result of an interaction between specific genetic factors and nonspecific insults during embryonic development. Dermatoglyphic abnormalities appear to mark these putative insults--providing information about the temporal sequence of aberrant developmental events as well as the organism's vulnerability to their adverse effects. In the present study, dermatoglyphic measures thought to mark first and second trimester development were examined in patients with schizophrenia and first degree relatives and compared with those of healthy controls to examine whether genetic factors may mediate this vulnerability. Both patients with schizophrenia and relatives exhibited dermatoglyphic abnormalities compared with controls. Patients were more likely to exhibit dermatoglyphic abnormalities indicative of early second trimester development, which suggests that vulnerability interacts with the timing of insults to produce overt disease. These findings indicate that the two-hit model, in which schizophrenia-specific genetic factors combine in an additive fashion with environmental insults to produce the illness, may be oversimplified. Rather, the data are consistent with a more complex model in which nonspecific genetic factors that increase susceptibility to developmental abnormalities interact with insults and specific genetic factors.

Adult↗
PubMed2003

A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype.

Smooth pursuit eye movement (SPEM) abnormalities in schizophrenia, although well described, are poorly understood. SPEMs are initiated by motion of an object image on the retina. During initiation, the eyes accelerate until they approximate target velocity and a state of minimal retinal motion is achieved. Pursuit is maintained through predictive eye movements based on extraretinal signals and corrections based on deviations from the fovea. Here, initiation and predictive pursuit responses were used to estimate the contributions of retinal and extraretinal signals to pursuit maintenance in schizophrenia patients' relatives. Relatives exhibited normal initiation, but had lower predictive pursuit gain compared with controls. Relatives had normal gain during pursuit maintenance, presumably by greater reliance on retinal error. This was confirmed by group differences in regression coefficients for retinal and extraretinal measures, and suggests that schizophrenia SPEM deficits involve reduced ability to maintain or integrate extraretinal signals, and that retinal error may be used to compensate.

Humans↗
PubMed2002

The effects of nicotine on specific eye tracking measures in schizophrenia.

BACKGROUND: The role of neuronal nicotinic receptors in the etiology and pathophysiology of schizophrenia has been suggested by postmortem findings as well as by linkage analysis implicating chromosome 15q14, the region where the alpha-7 nicotinic receptor gene is located. In addition, drug probe studies show that acute nicotine administration reverses sensory gating and eye-tracking deficits associated with the genetic liability for schizophrenia. The purpose of the current study was to examine the effects of acute administration of nicotine on specific measures of smooth pursuit eye movements and visual attention. METHODS: Twenty nine subjects with schizophrenia (15 smokers and 14 nonsmokers), and 26 healthy comparison subjects (15 smokers and 11 nonsmokers) completed testing. The effects of 1 mg of nicotine, administered by nasal spray, on smooth pursuit initiation, pursuit maintenance, and predictive pursuit were examined. RESULTS: Nicotine significantly improved eye acceleration during smooth pursuit initiation in both smoker and nonsmoker patients but had no effects in healthy subjects. The fact that patient initiation eye acceleration in response to nicotine was significantly higher than in healthy subjects suggests that the lack of effect in healthy subjects was not due to ceiling effects. Nicotine significantly improved pursuit gain during maintenance at a target velocity of 18.7 deg/sec. There were no effects of nicotine on visually guided and memory saccades, or visual attention (d' from a continuous performance task). CONCLUSIONS: Nicotine showed differential effects in schizophrenic patients compared to healthy subjects. These effects of nicotine were unlikely the result of differences in vigilance or sustained attention, because saccadic peak velocity, a sensitive measure of vigilance, and continuous performance task measures were not affected by nicotine. These findings are not thought to be an artifact of nicotine withdrawal effects at baseline, because the abstinence period was very short, and there were similar effects of nicotine on initiation in nonsmoker patients. These findings suggest an abnormality in neuronal nicotinic system functioning in schizophrenic patients.

Administration, Intranasal↗
PubMed2002

Effects of ketamine on leading saccades during smooth-pursuit eye movements may implicate cerebellar dysfunction in schizophrenia.

OBJECTIVE: Ketamine has proved a useful probe in the study of schizophrenia. Recent studies have shown that ketamine causes abnormalities in eye tracking similar to those seen in patients with schizophrenia. The authors examined the effects of ketamine on leading saccadic eye movements, a specific component of the smooth-pursuit response shown to be abnormal in schizophrenia patients and their relatives. METHOD: Twelve normal healthy volunteers received a 0.1 mg/kg bolus injection of ketamine or placebo in double-blind fashion during a smooth-pursuit eye-movement task. The number of leading saccades and the ratios of leading saccades to smooth-pursuit response time and to total saccadic eye-movement time were measured. RESULTS: Ketamine significantly increased the number of leading saccades and increased the leading saccade ratios for more slowly moving targets. Similar nonsignificant effects were noted at higher target speeds. Ketamine-induced abnormalities were similar to those observed in relatives of schizophrenia patients under drug-free conditions. CONCLUSIONS: These results suggest that neurotransmission mediated by N-methyl-D-aspartate (NMDA) is involved in eye-tracking abnormalities. The generation of disruptive leading saccades during smooth pursuit is thought to be mediated by frontal-thalamic-cerebellar circuitry. Evidence that the locus of this and other ketamine-induced smooth-pursuit eye-movement deficits involves NMDA receptor functioning in the cerebellum is suggested.

Adult↗
PubMed2002

Neurophysiological markers of vulnerability to schizophrenia: sensitivity and specificity of specific quantitative eye movement measures.

Eye-tracking deficits in schizophrenic patients and relatives have generated interest in using eye movements to mark schizophrenia liability. Efforts to develop specific quantitative measures have provided insight into the nature of the deficit and suggested what underlying neurophysiological mechanisms are involved. This study used receiver operating characteristic curve analyses to evaluate and compare the sensitivity, specificity, and overall accuracy of predicting disease liability using single and combined specific and global quantitative measures. Results indicate that measures of predictive pursuit and leading saccades significantly increased predictive accuracy compared with traditional global measures. Combining specific measures provided greater predictive accuracy compared with single measures. Implications for the use of specific eye movement measures to define schizophrenia-related phenotypes in genetic studies are discussed.

Adult↗