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Biomedical subjects

A Breier

Publications and source records attributed to A Breier.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1988

Principles of selectivity of sodium and potassium binding sites of the Na+/K+-ATPase. A corollary hypothesis.

The mechanisms whereby the sodium and potassium binding sites of heart sacrolemmal Na+/K+-ATPase (EC 3.6.1.3) distinguished between monovalent cations were investigated using methods of enzyme kinetics. The properties of the sodium binding sites were studied in the presence of 2,4,6-trinitrobenzenesulfonic acid in concentrations completely inhibiting the action of potassium on the enzyme. To test the selectivity of potassium binding sites, K+-p-nitrophenylphosphatase activity was employed as a model. The results suggest that the selectivity of Na+- and K+-binding sites of Na+/K+-ATPase may be due to two independent mechanisms: (i) The principle of key and lock (formation of coordination bounds); (ii) Optimal difference between solvatation energy (in the specific binding site) and hydration enthalpy of the respective cation.

Animals↗
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↗
PubMed1988

Small sample studies: unique contributions for large sample outcome studies.

There are many important issues relevant to the course of illness and outcome of chronic psychiatric disorders that are not readily amenable to investigation with existing large sample, quantitative methodology. For example, complex interactive phenomena that change over time, such as the longitudinal impact of changes in social and work function on levels of symptomatology, are particularly difficult to quantify and assess in large n studies. Small sample studies are advantageous because they offer the ability to examine the longitudinal interplay of a wide range of variables in individual patients. The small n approach is useful for delineating important new course variables, developing models of course change, and generating unique research hypotheses. In this article, small sample "qualitative" methodology is reviewed, and data derived from recent small n, intensive longitudinal studies are presented. Methodological issues related to addressing qualitative data in large sample, controlled studies are addressed, and specific research hypotheses generated by small sample studies for consideration in future large sample outcome studies are suggested. It is concluded that small sample studies offer unique contributions to the understanding of the determinants of course of illness.

Follow-Up Studies↗
PubMed1988

Plasma homovanillic acid as an index of central dopaminergic activity: studies in schizophrenic patients.

Despite the limitations of the dopamine hypothesis, compelling evidence remains that implicates dysfunction of CNS dopamine systems in the pathophysiology of schizophrenia. The longitudinal measurement of levels of plasma HVA has proved a useful tool in studying neuroleptic effects and has highlighted time-dependent effects as a potentially important facet of the mechanism of antipsychotic action of these drugs. Despite the good clinical correlates of plasma HVA levels, caution is needed in interpreting plasma levels of HVA with regard to CNS dopamine activity. The peripheral nervous system significantly contributes to levels of HVA that circulate in plasma. This issue is underscored by the fact that CSF HVA shows different neuroleptic response patterns than that seen in plasma. The administration of a peripherally acting MAO inhibitor to enhance the CNS "signal" in circulating levels of HVA does not resolve the "problem" of different CSF-plasma HVA neuroleptic response patterns. The possibility that mesocortical dopamine activity is reflected by CSF HVA is suggested by indirect evidence from clinical and preclinical studies. Future studies in which attempts are made at using both plasma and CSF HVA to enhance neurochemical and clinical correlates may help to advance our understanding of the contributions of specific CNS dopamine systems to schizophrenia.

Animals↗
PubMed1987

Prednisone decreases CSF somatostatin in healthy humans: implications for neuropsychiatric illness.

Several neuropsychiatric illnesses, including depression and Alzheimer's disease, are reported to be characterized by hypercortisolemia and by reduced levels of cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI). To investigate a possible causal linkage between these abnormalities we administered prednisone, 80 mg orally per day for 5 days, to 9 healthy volunteers. We observed significant prednisone-induced reductions in CSF-SLI. Moreover, the magnitude of these reductions was inversely related to the magnitude of prednisone-induced reductions in plasma ACTH levels, suggesting a functional interaction between circulating corticosteroids, central somatostatin and pituitary ACTH release.

Adrenocorticotropic Hormone↗
PubMed1987

Clinical and biochemical effects of verapamil administration to schizophrenic patients.

We administered verapamil hydrochloride, a calcium channel antagonist, to seven chronically ill schizophrenic patients for five weeks under double-blind, placebo-controlled conditions. No therapeutic effect was noted. Worsening in hostile and uncooperative behaviors and a syndrome of heightened emotional tone was observed during verapamil treatment and during the postverapamil placebo period. Verapamil produced significant increases in cerebrospinal fluid (CSF) and plasma levels of homovanillic acid and in plasma levels of prolactin, as well as significant decreases in plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol. Verapamil and its active metabolite, norverapamil, were partitioned into CSF with CSF/plasma ratios of 0.06 and 0.04, respectively. The lack of therapeutic effects of verapamil in schizophrenic patients differs from earlier reports of its usefulness in treating manic patients. The biochemical and clinical data from our study suggest the possibility that verapamil exerts behaviorally relevant central nervous system activity in schizophrenic patients.

Adult↗
PubMed1987

The effects of dexamethasone on plasma homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. Evidence for abnormal corticosteroid-catecholamine interactions in major depression.

We investigated the possible interactions between corticosteroids and catecholamines in depression by studying the effects of the synthetic glucocorticoid dexamethasone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) in a group of depressed patients and normal controls. In comparison with metabolite levels on a control day, normal controls showed a significant dexamethasone-induced increase in the plasma HVA level and a trend toward a decrease in the plasma MHPG level at 4 PM following dexamethasone administration (1 mg orally at 11 PM). Conversely, depressed patients, particularly those with psychotic features, showed a significant dexamethasone-induced increase in the plasma MHPG level and a blunting of the plasma HVA response relative to the normal controls. Dexamethasone-induced increases in the plasma MHPG level were directly correlated with the severity of depressive symptoms and with postdexamethasone cortisol levels in the depressed patients. These data suggest abnormal corticosteroid-catecholamine interactions in depression and, specifically, in depressed patients with psychotic features.

Adult↗
PubMed1987

Structural brain pathology in schizophrenia revisited. Prefrontal cortex pathology is inversely correlated with cerebrospinal fluid levels of homovanillic acid.

Computed tomography scan analysis of 35 schizophrenic patients, 26 medical patients, and 31 normal controls revealed significantly larger ventricular brain ratios and structural changes consistent with cortical atrophy in both schizophrenic and medical patients in comparison with normal controls. The schizophrenic patients, however, differed from both control groups in terms of greater prefrontal cortical markings consistent with prefrontal atrophy, and this finding correlated inversely with levels of cerebrospinal fluid homovanillic acid. Results from this study, in addition to replicating previous findings and addressing methodologic issues concerning controls, provide new evidence implicating abnormality of the prefrontal cortex in schizophrenia and link this abnormality to central nervous system dopaminergic function.

Adult↗