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Biomedical subjects

O M Wolkowitz

Publications and source records attributed to O M Wolkowitz.

At least 55 records · Page 3Linked to original sources
PubMed1990

Cerebrospinal fluid and plasma monoamine metabolites and their relation to psychosis. Implications for regional brain dysfunction in schizophrenia.

The relationship between central (cerebrospinal fluid [CSF]) and peripheral (plasma) monoaminergic metabolites and psychotic symptoms was examined in 22 drug-free schizophrenic inpatients. The CSF homovanillic acid levels did not differ significantly between patients and normal controls (n = 33). The CSF homovanillic acid levels, however, were negatively correlated with ratings of psychosis and positive symptoms, and the CSF homovanillic acid and 5-hydroxyindoleacetic acid levels correlated negatively with individual deficit symptoms. Stepwise and hierarchical multiple-regression analysis revealed that among monoaminergic measures, only the CSF and plasma homovanillic acid levels contributed significantly to the total Brief Psychiatric Rating Scale and positive symptom variance with negative and positive partial correlations, respectively. Levels of CSF 3-methoxy-4-hydroxyphenylglycol, but not of CSF norepinephrine, were significantly elevated in the schizophrenic patients compared with controls, and plasma 3-methoxy-4-hydroxyphenylglycol levels were positively correlated with negative symptoms. We discuss the potential implications of these findings for a model of dopaminergic dysfunction in schizophrenia involving distinct cortical and subcortical contributions.

Adult↗
PubMed1990

Prednisone effects on neurochemistry and behavior. Preliminary findings.

To evaluate the neurochemical, neuroendocrine, and behavioral effects of exogenous corticosteroids in humans, we administered prednisone (80 mg/d orally for 5 days) in a double-blind manner to 12 medically healthy volunteers. Behavioral measures were assessed before, during, and after prednisone administration in all 12 subjects, and cerebrospinal fluid biochemistry was assessed before and during prednisone administration in 9 of the subjects. Prednisone administration was associated with decreases in cerebrospinal fluid levels of corticotropin, norepinephrine, beta-endorphin, beta-lipotropin, and somatostatinlike immunoreactivity. No significant changes were noted in cerebrospinal fluid levels of alpha-melanocyte-stimulating hormone, corticotropin-releasing hormone, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, or 5-hydroxyindoleacetic acid. No consistent or significant group mean changes were observed in structured behavioral ratings, although 9 (75%) of the volunteers studied reported mild behavioral changes while receiving prednisone. Correlations between the neurochemical and behavioral changes are discussed.

Adult↗
PubMed1990

Prednisone effects on blood-brain barrier permeability and CNS IgG synthesis in healthy humans.

Corticosteroids reportedly decrease blood-brain barrier (BBB) permeability and/or IgG synthesis in patients with multiple sclerosis or brain tumors. However, these effects have not been studied in healthy humans. We investigated the effects of prednisone, 80 mg/day for five days, on the ratio of cerebrospinal fluid (CSF) albumin/serum albumin, a measure of blood-brain barrier (BBB) permeability, and on CSF and serum IgG levels in six healthy, normal volunteers. We found significant steroid-induced decreases in serum and CSF albumin levels and in serum IgG levels. However, we found only a nonsignificant decrease in BBB permeability and no significant change in CNS IgG synthesis. These findings, based on a small number of volunteers, suggest that it may be difficult to further decrease BBB permeability and CNS IgG synthesis in medically healthy subjects.

Adult↗
PubMed1990

Neurochemical and neural mechanisms of positive and negative symptoms in schizophrenia.

It is difficult to come away from review of pharmacologic and metabolite studies without concluding that dopaminergic mechanisms play a significant role in mediating both negative and positive symptoms. Nevertheless, the characteristics of dopaminergic involvement are unclear. Whereas compelling evidence continues to link the mechanism of action of neuroleptic drugs, including therapeutic effects on negative and positive symptoms, to blockade of D2 receptors, neuroleptic-induced alterations in dopaminergic function are time-dependent and may include reductions in variability as well as in net dopamine activity. Moreover, pharmacologic enhancement of dopaminergic function may at least transiently improve symptomatology (negative greater than positive) and levels of CSF HVA appear to be reduced or are negatively correlated with symptoms in some schizophrenic patients. Thus, there is support for both increased and decreased dopamine function in schizophrenia. Functional brain imaging has, after only a few years of application, made significant contributions to our understanding of the pathophysiology of schizophrenia. Studies of cerebral metabolism and regional CBF have shown remarkable consistency in their identification of abnormal function of the frontal cortex in schizophrenia. It should be pointed out, however, that agreement across studies remains largely conceptual with significant discrepancies still existing with regard to the precise localization of dysfunction and its relationship to cognitive activation. Although less well documented than 'hypofrontality' itself, negative symptomatology appears to bear some relationship to this defect. The idea that positive symptoms might be associated with increased subcortical and/or metabolism is less well supported. The recent advances in our understanding of structure and function of CNS dopaminergic systems may help to integrate these two bodies of data into more dynamic models of dopaminergic defects in schizophrenia. For example, the concept that diminished mesocortical coupled with increased subcortical dopaminergic activity might be a 'substrate' for psychosis is compatible with neurochemical evidence suggesting both diminished and enhanced dopaminergic processes as well as with metabolic hypofrontality. Better understanding of the regulatory mechanisms involved in establishing functional balance between cortical and subcortical systems might, therefore, identify new possibilities for biological dysfunction in schizophrenia. The recent study by Weinberger et al. which correlates CSF HVA levels with neuropsychologically induced frontal CBF is an example of how neurochemistry can enhance brain imaging data.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗
PubMed1990

Cognitive effects of corticosteroids.

In three independent studies with different designs and groups of subjects, the authors found that 1) depressed patients who did not suppress cortisol when given dexamethasone (compared to suppressors and normal control subjects), 2) healthy volunteers given a single 1-mg dose of dexamethasone (compared to those given placebo), and 3) healthy volunteers given 80 mg/day of prednisone for 5 days (compared to those given placebo) all made significantly more errors of commission in verbal memory tasks, with no significant change in their rates of errors of omission. These findings raise the possibility of specific corticosteroid-related cognitive impairments.

Adrenal Cortex Hormones↗
PubMed1990

Plasma norepinephrine in chronic schizophrenia.

Several lines of evidence indicate altered noradrenergic function in schizophrenia. The authors examined resting, standing, and change (standing minus resting) in plasma norepinephrine levels in 14 drug-free patients with chronic schizophrenia or schizoaffective disorder and in 33 age- and sex-matched healthy volunteers. Schizophrenic patients had significantly higher resting and standing plasma norepinephrine levels and significantly greater change. Resting and standing levels were significantly related to positive and negative symptoms. There was a significant positive correlation between resting plasma and CSF norepinephrine levels and a significant negative correlation between CSF homovanillic acid and resting, standing, and change in plasma norepinephrine levels.

Adult↗
PubMed1990

Use of the dexamethasone suppression test with mentally retarded persons: review and recommendations.

The correct methodology for performing the Dexamethasone Suppression Test (DST), which has been widely studied in psychiatry for its possible utility as a laboratory test of depression, was reviewed. Factors that may invalidate the test by producing false-positive or false-negative results and current recommendations regarding using the test were discussed. Studies of the use of the DST for patients with mental retardation as well as other patients displaying atypical symptoms of depression, such as children and demented elderly persons, were reviewed.

Adult↗
PubMed1989

Fluphenazine treatment reduces CSF somatostatin in patients with schizophrenia: correlations with CSF HVA.

CSF somatostatin and homovanillic acid (HVA) were measured in 14 schizophrenic patients while they were drug-free and during chronic fluphenazine treatment. CSF somatostatin was significantly reduced and CSF HVA was significantly elevated (p less than 0.002) during fluphenazine treatment. There was a trend toward correlation between CSF somatostatin and CSF HVA in the 14 schizophrenic patients when drug-free (r = 0.49, p less than 0.07) and fluphenazine-treated (r = 0.47, p less than 0.08). When examined in a larger group (n = 46) of drug-free schizophrenics, this relationship was highly significant (r = 0.59, p less than 0.001). These clinical data are consistent with preclinical evidence indicating a functional interaction between CNS somatostatin and dopamine systems.

Adult↗
PubMed1989

Specificity of plasma HVA response to dexamethasone in psychotic depression.

Earlier reports have suggested that dexamethasone significantly increases levels of plasma homovanillic acid (HVA) in normal subjects, but that this effect may be altered in some depressed patients. To investigate the specificity of such alterations, we administered dexamethasone (1 mg p.o. at 11 p.m.) to 33 normal subjects, 27 depressed patients (8 with psychotic features), and 16 schizophrenic patients. Plasma for assay of cortisol and HVA was obtained at 4 p.m. before and on the day following dexamethasone administration. Dexamethasone induced significant increases in plasma HVA in the normal subjects and in the schizophrenic patients, but not in the depressed patients. Indeed, psychotically depressed patients tended to show a dexamethasone-associated decrease in plasma levels of HVA. In contrast to cortisol "suppression" or "nonsuppression," dexamethasone-induced changes in plasma levels of HVA (i.e., increases or decreases) sensitively and specifically discriminated between patients with affective and nonaffective psychoses.

Adult↗
PubMed1989

High prevalence of visual hallucinations in research subjects with chronic schizophrenia.

The authors examined the prevalence of visual hallucinations in severely ill hospitalized research subjects with carefully diagnosed chronic schizophrenia and found it to be high. A chart review of 100 discharged subjects revealed documentation of visual hallucinations in 32%, and a prospective examination of 43 additional subjects revealed a history of visual hallucinations in 56% (N = 24). Also, the fact that in 43% of the patients with visual hallucinations the history of visual hallucinations was first documented during the research ward work-up suggests that clinicians frequently do not inquire about visual hallucinations in patients with chronic schizophrenia.

Chronic Disease↗
PubMed1988

Alprazolam augmentation of the antipsychotic effects of fluphenazine in schizophrenic patients. Preliminary results.

Alprazolam was added, under double-blind conditions, to stable fluphenazine hydrochloride regimens in 12 symptomatic, chronically ill inpatients with schizophrenia. The addition of alprazolam was associated with significant, albeit modest, reductions in global psychosis, thought disorder, and paranoia ratings, with a return to pretreatment levels on discontinuation of alprazolam treatment. Improvement in "negative symptoms" such as emotional withdrawal paralleled the changes in "positive symptoms" but did not, in itself, reach statistical significance. There were no significant changes in group mean plasma levels of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol during alprazolam treatment, although group mean serum cortisol levels were significantly decreased by alprazolam treatment. Patients who responded favorably to alprazolam treatment were significantly more psychotic or anxious before treatment, were older, showed significant alprazolam-associated reductions in plasma levels of homovanillic acid, and had significantly more prominent prefrontal cortex atrophy on computed tomographic scans than patients in whom alprazolam was without therapeutic effect. These preliminary data, based on a small sample, suggest that some patients with schizophrenia who are only partially responsive to standard neuroleptic treatment may benefit from the addition of triazolobenzodiazepines, such as alprazolam.

Adult↗
PubMed1988

Early parental loss and development of adult psychopathology.

We assessed the effect of parental loss during childhood on the development of psychopathology in 90 adults. The subjects with a history of adult psychopathology (PATH group), in comparison with subjects with no history of a psychiatric disorder (NO PATH group), had poorer quality of childhood home life and personal adaptation subsequent to parental loss as assessed by the Home Life and Personal Adaptation (HAPA) scale developed by us. Total HAPA scale scores were the single most powerful predictor of adult psychopathology, accounting for correct prediction of adult psychopathology in 80% (72/90) of the subjects. The PATH subjects had significantly increased plasma levels of cortisol and beta-endorphin immunoreactivity. Moreover, cortisol and adrenocorticotropic hormone levels significantly correlated with total HAPA scores. First-degree family history of psychiatric disorders, age at loss, and parental vs maternal loss were not significantly different between PATH and NO PATH subjects. We conclude that the quality of home life subsequent to early parental loss is critically related to the development of adult psychopathology. The hypothesis that early trauma results in enduring neuroendocrine alterations in hypothalamic-pituitary-adrenal axis function is examined.

Adaptation, Psychological↗
PubMed1988

Neurobiological effects of lumbar puncture stress in psychiatric patients and healthy volunteers.

Several existing laboratory-based stress paradigms have significant shortcomings for assessing neurobiological correlates of stress in healthy volunteers and severely ill psychiatric patients. We have examined neuroendocrine effects of stress associated with the lumbar puncture (LP) procedure in drug-free depressed and schizophrenic patients and healthy volunteers. Healthy volunteers and depressed patients had significant stress-induced elevations in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and growth hormone associated with LP. In contrast, schizophrenic patients had no significant elevations in any of the neuroendocrine parameters. Depressed patients' cerebrospinal fluid norepinephrine levels were negatively correlated with stress-induced activation of the hypothalamic-pituitary-adrenal axis. In addition, depressed patients' basal plasma cortisol levels were strongly predictive of stress-related elevations in ACTH, cortisol, and growth hormone. Furthermore, stress-induced changes in schizophrenic patients' cortisol and ACTH levels were not correlated.

Adrenocorticotropic Hormone↗