Inhibition of pyruvate dehydrogenase complex by antipsychotic drugs.
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Biomedical subjects
Publications and source records attributed to J Volavka.
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This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients.
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This study analyzed interrelationships among plasma level of haloperidol (HAL), electroencephalographic (EEG) changes, and clinical response in 37 acutely exacerbated schizophrenic patients after a 6-week period of treatment. Two hypotheses were tested: (1) EEG theta response to HAL depends on levels of HAL in plasma, and this relationship is expressed in patients showing a clear clinical response (responders). (2) Responders and nonresponders are characterized by a different neuroleptic EEG profile. EEG examinations (resting, waking EEG) were performed at study entry, end point of the placebo period ("baseline"), and weekly during the entire HAL treatment period. EEG response was measured by power spectral changes in four frequency bands (delta, theta, alpha, and beta); clinical response was assessed by the Brief Psychiatric Rating Scale. There was a significant relationship between HAL plasma levels and EEG theta activity for treatment responders, whereas no relationship was detected for the nonresponders. Furthermore, there were EEG changes (in the delta and alpha bands) that depended on clinical response but did not show any relationship, either in responders or nonresponders, to HAL plasma levels. These results supported both hypotheses.
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In a visual analysis of electroencephalograms (EEGs) obtained in 33 melancholic men before and after six brief pulse right unilateral, left unilateral, or bilateral electroconvulsive therapy (ECT) treatments, the authors were unable to detect the relation between therapeutic outcome and differential hemispheric lateralization of ECT-induced EEG slowing that had been reported previously for sine wave ECT at the same clinical site. These results may be related to differences in neurophysiologic effects between sine wave and brief pulse ECT, and do not support the hypothesis that lateralization of ECT-induced EEG slowing is central to the antidepressant effects of ECT.
A 13-item questionnaire was constructed to assess risk factors for HIV infection among 476 patients newly admitted over a one-year period to a state psychiatric hospital in New York City. Because psychopathology can affect patients' self-reports, the validity of the instrument was established by HIV antibody tests in a subset of 352 patients. Results of the questionnaire indicated that the 352 patients were almost equally divided between the high-risk and low-risk categories. HIV seroprevalence was .6 percent among the low-risk patients, but 14.4 percent among the high-risk patients. The findings suggest that a screening program to detect HIV-positive patients should be undertaken in this population, that it should be focused on the high-risk subgroup, and that the questionnaire can be used to define that subgroup. However, results of the study may not generalize to other geographic areas.
The antecedents of violent crime may include childhood victimization, head injuries, and alcohol and drug abuse. Neuropsychological and neuropsychiatric findings suggest temporal and frontal lobe dysfunctions in violent offenders; these dysfunctions appear to be more pronounced in the dominant hemisphere. Recent studies implicate disturbances of central serotonergic functions in impulsive homicide and arson. These results provide an adequate rationale for larger interdisciplinary studies using neurochemical, neuropsychiatric/neuropsychological, and psychosocial methods on the same subjects.
This study analyzed the relationship between pretreatment electroencephalogram (EEG) and response to haloperidol medication in a group of acutely exacerbated schizophrenic patients (n = 34). Improvement was assessed after 3 and 6 weeks of treatment; it was measured globally, as decrease in the total score on the Brief Psychiatric Rating Scale (BPRS), as well as multidimensionally through the individual BPRS factors. Relative powers from four clinical EEG frequency bands were employed as predictor variables. Baseline alpha activity was significantly related to clinical response. Higher alpha values were associated with poorer response to treatment. Specifically, improvements on the "thought disturbance" and "hostility-suspiciousness" factors underlied the relationship between the pretreatment EEG and outcome.
Twenty-one consecutive right-handed male psychiatric inpatients treated on a unit designed for the management of violent behavior were given computerized EEGs. We recorded their violent behaviors, the number of staff interventions needed to control their behavior, and their medications. The number of instances of violence as well as the number of staff interventions were related to increased delta band activity and to decreased alpha band activity in the temporal and the parietooccipital areas. These relationships were independent of the current medications and of the length of stay on the special unit. Furthermore, our results demonstrate that violence is very significantly related to the hemispheric asymmetry in EEG for the frontotemporal derivations. With increased levels of violence there was a greater level of delta power in the left compared with the right.
The seroprevalence of the human immunodeficiency virus (HIV) in 515 patients consecutively admitted to a state psychiatric hospital in New York City was 8.9%. There were 365 patients whose results were individually traceable; the remaining 150 patients were tested anonymously. Risk factors including parenteral drug abuse, male homosexual behaviors, and other sexual behaviors were studied in the traceable patients. Logistic regressions indicated that parenteral drug abuse was the main risk factor in both males and females. In females, two additional factors were significant: sex with parenteral drug users or with partners who have the acquired immunodeficiency syndrome (AIDS), and sex with bisexual men. Females with bipolar disorders were particularly likely to report sex with parenteral drug users or with partners who have AIDS.
Because overlapping psychometric scales are used frequently in psychiatric research, examination of the relationship between scales has become increasingly important. The concept of relationship is the focus of this article. By way of illustration, the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS) were compared for correlation and redundancy. Since these scales are frequently represented by derived summary variables (e.g., factors, total scores), it is also important to assess the effect of such representation on measures of relationship. The SANS and the BPRS were found to be highly intercorrelated. Nevertheless, the individual items and the subscale scores of the SANS contain information independent from the BPRS: the best BPRS predictor variates can explain only approximately half of the total variance of the SANS. When the SANS, however, is represented by a single variable (composite score), it becomes highly redundant with the anergia factor of the BPRS.
The authors review the development and the controversies of the neuroleptic threshold theory. According to this theory, the minimum effective antipsychotic dose of a neuroleptic ("threshold dose") correlates with the appearance of "fine motor" symptoms (micrography) as opposed to the appearance of manifest or "coarse motor" extrapyramidal side effects. About half of the acutely exacerbated schizophrenic patients respond to threshold doses, but no predictors are known to characterize the responders. The neuroleptic threshold doses were found to be low, and the low dose treatment strategy is supported by the results of current PET and neuroleptic plasma level studies.
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This double-blind, placebo-controlled study tested the effectiveness of tryptophan (TRP) in the treatment of aggressive psychiatric inpatients. After a baseline observation period of 1 month, patients were randomly assigned to treatment either with TRP (up to 6 g/day) or with placebo. There were 10 subjects in each treatment group. These treatments were administered for 25-35 days, after which the patients were observed for 1 month. Throughout this study, patients were receiving other medications. Injections of antipsychotics and sedatives were administered as needed to control agitated or violent behavior. Blood levels of TRP and other large neutral amino acids were obtained repeatedly, and ratios between TRP and other amino acids were computed. These analyses confirmed significant increases of TRP ratios in TRP-treated patients. TRP treatment had no effect on the number of violent incidents, but it significantly reduced the need for injections of antipsychotics and sedatives. The study thus provided indirect support for beneficial effects of TRP in aggressive psychiatric inpatients.
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Self reports of criminal activity are known to be valid in general populations. Little is known about the validity of self-reports of crime in psychiatric inpatients. A group of 41 psychiatric inpatients had their self-reported arrests contrasted with their official arrest records. Sixty-six percent of the patients gave accurate reports. Twelve percent denied having arrests when their record showed arrests. Twenty-two percent reported arrests when their official records showed none. The authors discuss the implications of these findings.
Investigations of assaults in psychiatric hospitals have found that a small proportion of inpatients are responsible for a large percentage of the violence that occurs. In a large state hospital patients who were repeatedly violent (recidivists) were compared with patients who were violent only once or twice (nonrecidivists), and the relationships between repeatedly violent behavior and gender, age, and diagnosis were examined. All reports of violent incidents over a six-month period for a population of 1,552 inpatients--a total of 497 incidents involving 313 patients--were reviewed. Seventy patients were involved in three or more incidents each and were responsible for 53 percent of all violence. Recidivist men inflicted serious injuries at a rate ten times higher than that for all the other violent patients. Recidivist women were significantly younger than nonrecidivist assaultive women and were about the same mean age as the assaultive men. Recidivist women were also more likely to have organic brain disorder or personality disorder.