PubMed Health⌕ Search

Biomedical subjects

G K Thaker

Publications and source records attributed to G K Thaker.

48 records · Page 3Linked to original sources
PubMed1987

Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment.

A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.

Adult↗
PubMed1986

Dopamine agonist treatment of schizophrenia with N-propylnorapomorphine.

We administered N-propylnorapomorphine, a potent aporphine-family dopamine (DA) agonist, to schizophrenic patients with active psychotic symptoms. After acute administration a significant antipsychotic action of N-propylnorapomorphine, maximal at an oral dose of 19 mg, was noted. The antipsychotic action predominated in subjects with neuroleptic-responsive symptoms, not in neuroleptic-nonresponders. However, when N-propylnorapomorphine was administered on a subchronic dosage schedule, no antipsychotic effect occurred. These observations suggest a rapid-onset tolerance phenomenon of psychosis to N-propylnorapomorphine and are consistent with results from preclinical experiments. These data support the idea that the acute antipsychotic response of DA agonists is mediated by the DA autoreceptor but fail to provide evidence for the potential clinical usefulness of this treatment approach.

Administration, Oral↗
PubMed1986

Neuronal cholecystokinin and schizophrenia: pathogenic and therapeutic studies.

Neuroleptic-free schizophrenic patients received caerulein, a potent analogue of cholecystokinin octapeptide, in a fixed- and rising-dose schedule. In addition, neuroleptic-treated patients received a single dose of the peptide with a 4-week follow-up. No significant change in mental status was observed after any of these administration schedules. Peak plasma levels of caerulein were noted at 20-30 min after IM administration; at this time no changes in cortical evoked potential were demonstrated. Furthermore, levels of cholecystokinin were not found to be reduced, but were in fact elevated in lumbar cerebrospinal fluid of schizophrenic patients. These data argue against the antipsychotic efficacy of systemic caerulein administration and, because evidence of CNS response to CCK is lacking, suggest that other pharmacologic strategies may be necessary to effectively modify central peptide systems with systemically administered drugs.

Adult↗
PubMed1985

GABA dysfunction in the pathophysiology of tardive dyskinesia.

Pharmacologic treatments which diminish central dopaminergic transmission improve symptoms of tardive dyskinesia (TD). These clinical data, supported by results from animal model studies, have provided a basis for the dopamine (DA) receptor hypersensitivity hypothesis of TD. Since its initial formulation, however, knowledge of the multiple effects of prolonged neuroleptic administration in mammalian CNS has greatly expanded. Clinical and animal model studies carried out independently now both suggest that GABA-mediated neuronal tracts of the basal ganglia are important, perhaps pivotal, in TD. Thus, we would extend the DA hypothesis of TD to include the idea that neuroleptic-induced DA receptor hypersensitivity in striatum results in GABA system hypofunction in striatal projection areas in those individuals who develop TD.

Brain↗
PubMedDate not supplied

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 one's observed in patients with unilateral left hemisphere lesions.

Adult↗
PubMedDate not supplied

Children and adolescents with psychotic disorder not otherwise specified: a 2- to 8-year follow-up study.

Although psychotic phenomena in children with disruptive behavior disorders are more common than expected, their prognostic significance is unknown. To examine the outcome of pediatric patients with atypical psychoses, a group of 26 patients with transient psychotic symptoms were evaluated with clinical and structured interviews at the time of initial contact (mean age, 11.6 +/- 2.7 years) and at follow-up 2 to 8 years later. Measures of functioning and psychopathology were also completed at their initial assessment. Risk factors associated with adult psychotic disorders (familial psychopathology, eyetracking dysfunction in patients and their relatives, obstetrical complications, and premorbid developmental course in the proband) had been obtained at study entry. On follow-up examination (mean age, 15.7 +/- 3.4 years), 13 patients (50%) met diagnostic criteria for a major axis I disorder: three for schizoaffective disorder, four for bipolar disorder, and six for major depressive disorder. The remaining 13 patients again received a diagnosis of psychotic disorder not otherwise specified (NOS), with most being in remission from their psychotic symptoms. Among this group who had not developed a mood or psychotic disorder, disruptive behavior disorders were exceedingly common at follow-up and were the focus of their treatment. Higher initial levels of psychopathology, lower cognitive abilities, and more developmental motor abnormalities were found in patients with a poor outcome. Obstetrical, educational, and family histories did not differ significantly between the groups. Through systematic diagnostic evaluation, children and adolescents with atypical psychotic disorders can be distinguished from those with schizophrenia, a difference with important treatment and prognostic implications. Further research is needed to delineate the course and outcome of childhood-onset atypical psychoses, but preliminary data indicate improvement in psychotic symptoms in the majority of patients and the development of chronic mood disorders in a substantial subgroup.

Adolescent↗
PubMedDate not supplied

PET-FDG test-retest reliability during a visual discrimination task in schizophrenia.

OBJECTIVE: Reliability of assessment is important in any kind of neuropsychiatric study, but is particularly pivotal in schizophrenia research where symptom instability is common. MATERIALS AND METHODS: Two fluorodeoxyglucose PET scans, 1 week apart, were carried out in schizophrenic patients while they were performing a simple visual discrimination task. Subject and scan conditions were held constant. Regional metabolic rates of glucose utilization were calculated as absolute and scaled; they were compared using correlational statistics. RESULTS: Average differences between scans were 5-9% for the parietal and occipital cortices, but 1-3% for other cortical areas, differences comparable with reported variances in normal controls. CONCLUSION: These results suggest that test-retest variance in metabolic imaging in schizophrenia is relatively low and that task performance increases metabolic stability in brain areas unrelated to task performance.

Adult↗