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Biomedical subjects

O Wolkowitz

Publications and source records attributed to O Wolkowitz.

15 recordsLinked to original sources
PubMed2006

Catecholamine response to methamphetamine is related to glucocorticoid levels but not to pleasurable subjective response.

INTRODUCTION: Corticosteroids may modulate addiction. We previously described subjective, physiological, and endocrine effects of 0.5 mg/kg of intravenous methamphetamine after augmenting cortisol level with hydrocortisone or blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone in a double-blind, balanced crossover study. Although the pharmacologic manipulations produced the expected hormonal changes, pleasurable subjective effects of methamphetamine were unchanged. Metyrapone was followed by frequent premature ventricular complexes (PVCs) in two subjects during methamphetamine administration. In order to better understand these results, we examined changes in two plasma catecholamine metabolites, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and their relationship to the previously reported hormonal changes and physiological and subjective responses. METHODS: Plasma from 10 methamphetamine subjects from the earlier study was assayed for HVA and MHPG by high performance liquid chromatography. RESULTS: HVA levels were greater after hydrocortisone or metyrapone pretreatment compared to placebo, and MHPG levels were greater after metyrapone pretreatment. Hydrocortisone pretreatment diminished HVA and MHPG increases after methamphetamine (perhaps explaining the lack of expected increase in pleasurable effects), but metyrapone did not. HVA and MHPG concentrations were not correlated with pleasurable drug effects but were inversely related to reports of "Bad Drug Effect." Increases in MHPG and DHEA concentrations were positively correlated. Metyrapone pre-treated subjects with PVCs had lower HVA and MHPG concentrations. CONCLUSION: Raising cortisol concentration and blocking cortisol synthesis did not produce opposite effects, perhaps because of metyrapone's effect on the hypothalamic-pituitary-adrenal axis, its stress-like effects, and its effects on neurosteroids.

Adult↗
PubMed1996

The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients.

Thirty chronically hospitalized, refractory schizophrenic patients were evaluated while on typical neuroleptics and again after 12 weeks of clozapine treatment. Patients demonstrated small but statistically significant reductions in total Brief Psychiatric Rating Scale (BPRS) symptoms, need for seclusion and restraint, and PRN medications, and they frequently were transferred to a less restrictive treatment environment. Neuropsychological test data from a subset of patients suggested improvement on measures of verbal fluency and graphomotor speed, but deterioration on measures of visual memory and executive/frontal ability. Clozapine's different effects on multiple neurotransmitter systems may be responsible for its mixed effects on cognitive abilities. No significant relationships were found between symptom reduction, cognitive improvement, and transfer to a less restrictive environment.

Adult↗
PubMed1993

Neuropsychiatric effects of anabolic steroids in male normal volunteers.

OBJECTIVE: To evaluate the acute effects of anabolic steroids on mood and behavior in male normal volunteers. DESIGN: A 2-week, double-blind (subject and rater), fixed-order, placebo-controlled crossover trial of methyltestosterone. SETTING: An inpatient research unit at the National Institutes of Health. SUBJECTS: A volunteer sample of 20 men who were medication free, free of medical and psychiatric illness, not involved in athletic training, and had no prior history of anabolic steroid use. INTERVENTION: A sequential trial for 3 days each of the following four drug conditions: placebo baseline, low-dose methyltestosterone (40 mg/d), high-dose methyltestosterone (240 mg/d), and placebo withdrawal. MAIN OUTCOME MEASURES: Mood and behavioral ratings were completed during each drug condition and included both subjective and objective measures. RESULTS: Significant (P < .05) albeit subtle increases in symptom scores were observed during high-dose methyltestosterone administration compared with baseline in positive mood (euphoria, energy, and sexual arousal), negative mood (irritability, mood swings, violent feelings, and hostility), and cognitive impairment (distractibility, forgetfulness, and confusion). An acute manic episode was observed in one of the 20 subjects, representing a 5% incidence, even under these conservative conditions. An additional subject became hypomanic. Baseline characteristics including family psychiatric history or previous drug abuse did not predict symptom changes. CONCLUSION: This is the first placebo-controlled prospective study demonstrating the adverse and activating mood and behavioral effects of anabolic steroids.

Adolescent↗
PubMed1993

Beneficial effects of nalmefene augmentation in neuroleptic-stabilized schizophrenic patients.

It was postulated that chronic blockade of the opioid system in neuroleptic-stabilized schizophrenic patients would have a beneficial behavioral effect. Eleven neuroleptic-stabilized psychotic inpatients received augmentation with nalmefene for an average of 36.7 days in a double-blind placebo-controlled study. The patients exhibited significant reductions in Bunney-Hamburg psychosis ratings and the Brief Psychiatric Rating Scale thinking disturbance subscale during the augmentation period. This study presents preliminary data supporting the hypothesis that chronic augmentation of neuroleptic-stabilized schizophrenic patients with opiate antagonists is beneficial.

Adolescent↗
PubMed1992

Selective effects of triazolam on memory.

The effects of benzodiazepine (triazolam 0.25 and 0.50 mg) on different aspects of cognitive function were assessed. Triazolam impaired free recall and recognition of information presented after drug administration. In contrast to these impairments in explicit memory, a memory function that did not require conscious awareness was not altered by triazolam. Similarly, triazolam did not affect subjects' abilities to access semantic memory.

Adult↗
PubMed1992

Measurement and interpretation of changes in memory in response to drug treatments.

Drug-induced changes in cognitive functions such as memory are generally domain specific rather than general effects, that is, only some components of memory are altered. Changes in memory can be secondary to alterations in other cognitive domains such as attention, or non-cognitive domains (mood and arousal), or the direct result of alterations on those neurobiological systems that determine memory functions. The selective memory impairing effects of benzodiazepines are used to illustrate how cognitive neuroscience methods and theory can be useful in assessing the memory changes produced by psychoactive drugs.

Animals↗
PubMed1986

Chronic corticosterone administration in rats: behavioral and biochemical evidence of increased central dopaminergic activity.

Chronic corticosteroid treatment in humans in frequently complicated by behavioral changes. The present study suggests that chronic steroid administration in rats has distinct neurochemical consequences which are behaviorally relevant. Ten male Sprague-Dawley rats received 7 daily injections of corticosterone, following which they exhibited increased caudate homovanillic acid as well as an attenuated decline in vertical and ambulatory movement (functional measures of dopamine activity) compared to placebo-treated rats. A subgroup of steroid-treated rats which was more behaviorally responsive to corticosterone also showed increased caudate 5-hydroxyindole acetic acid and decreased prefrontal cortex dopamine and serotonin. These results are discussed in relation to the known behavioral side effects of chronic corticosteroid administration in man and the psychiatric manifestations of naturally occurring states of hypercortisolemia.

Animals↗
PubMed1986

Benzodiazepine sensitivity in normal human subjects.

Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.

Adult↗
PubMed1986

Suicide and aggression in schizophrenia. Neurobiologic correlates.

In this study of schizophrenic patients, we were unable to find an association between past history of suicide attempt and levels of CSF amine metabolites, response to DST, and ventricular size by CT scan, neurobiologic variables each of which have been reported to be associated with attempted suicide in some patient groups. Our data, however, demonstrate the marked responsiveness of measures of aggressive behavior to neuroleptic treatment, suggesting a dopaminergic involvement in these behaviors when observed in the presence of overt psychotic symptoms. Some support for an association between decreased CNS serotonin function and aggressive behavior was found in drug-free schizophrenics, although difficulty in separating illness from trait factors is an important confounding variable. The need for clinical interventions required to treat severely disturbed and aggressive behavior in the schizophrenic patients studied could not be predicted by any of the neurobiologic variables.

Aggression↗
PubMed1986

The corticotropin-releasing hormone stimulation test in chronic schizophrenia.

During a drug-free period a group of schizophrenic subjects (N = 9) showed normal mean basal plasma ACTH and cortisol levels in association with normal plasma ACTH and cortisol responses to an infusion of corticotropin-releasing hormone (CRH). Administration of fluphenazine had no effect on basal ACTH and cortisol levels or their responses to CRH (N = 8). These data differ from those previously reported in depressed patients, who showed elevated basal cortisol values in association with a blunted ACTH response to CRH, and add to a growing body of literature which suggests that hypothalamic-pituitary-adrenal regulation is less disturbed in schizophrenia than in depression.

Adrenocorticotropic Hormone↗
PubMed1984

Development of differences in response latencies to right and left visual fields.

Robust lateralization developed in right-handed adults who were asked to judge letter pairs as "same" or "different" during 4608 trials. By the end of the first two blocks (768 trials) "same" responses were favored when presented in the RVF (transmitted directly to the left hemisphere) and "different" responses were favored when presented in the LVF (transmitted direction to the right hemisphere). This gradually reversed over sessions with "same" responses becoming faster for letters presented in the LVF, and "different" responses becoming faster for stimuli presented in the RVF. The laterality acquired under these conditions was cumulative and reproducible, appeared in all 16 subjects, and was preserved between sessions a week apart. The data suggest that laterality is a flexible and reversible characteristic of the human brain even when stimulus and task remain constant.

Discrimination Learning↗