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Biomedical subjects

O M Wolkowitz

Publications and source records attributed to O M Wolkowitz.

At least 73 records · Page 4Linked to original sources

Alternate-day corticosteroid treatment, mood and plasma HVA in patients with systemic lupus erythematosus.

Corticosteroid therapy may produce alterations in mood. Furthermore, several monoamines, including dopamine, have been implicated in the regulation of mood. We, therefore, examined the relationship between alterations in mood and plasma homovanillic acid (HVA) levels in patients on alternate-day corticosteroid treatment. Although several patients had substantial alterations in mood, there was no significant difference in plasma HVA levels between the on- and off-medication day. Furthermore alterations in depression and anxiety levels were not related to plasma HVA levels. The implications of these findings are discussed.

Adult↗

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↗

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↗

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↗

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↗

Diazepam-induced amnesia: a neuropharmacological model of an "organic amnestic syndrome".

Diazepam has well-known amnestic properties. These effects, however, are selective for certain psychobiologically distinct memory functions. In this study, incremental doses of diazepam administered to 10 normal volunteers selectively impaired anterograde episodic memory and attention while totally sparing access to information in long-term memory (semantic or knowledge memory). This pattern of disruption mimics that seen in patients with organic amnesias and is in sharp contrast to the pattern seen in patients with dementia. These findings provide a framework for defining specific psychobiological determinants of cognitive failure.

Adult↗

Controllable and uncontrollable stress in humans: alterations in mood and neuroendocrine and psychophysiological function.

The authors exposed 10 healthy human volunteers to the stress of loud (100 dB) noise under controllable and uncontrollable conditions on two separate days. Subjects reported higher self-ratings of helplessness, lack of control, tension, stress, unhappiness, anxiety, and depression; had greater hypothalamic-pituitary-adrenal axis function as measured by elevations in plasma adrenocorticotropic hormone; and had higher levels of sympathetic nervous system and electrodermal activity after the uncontrollable stress condition than after exposure to controllable stress. Thus, lack of control over even a mildly aversive stimulus can produce alterations in mood as well as neuroendocrine and autonomic nervous system changes in healthy subjects.

Acoustic Stimulation↗

Neuroleptic responsivity of negative and positive symptoms in schizophrenia.

The authors prospectively examined the effects of double-blind, placebo-controlled neuroleptic withdrawal and administration on ratings of negative and positive symptoms in 19 young patients with chronic schizophrenia. Negative symptoms were significantly reduced by neuroleptic treatment, and negative and positive symptoms demonstrated similar patterns of reduction and exacerbation during neuroleptic treatment and withdrawal, respectively. The changes in negative and positive symptoms induced by neuroleptic treatment and withdrawal were not significantly correlated, however. The negative and positive symptom profiles of individual patients were significantly altered by neuroleptic treatment, indicating limitations to the cross-sectional classification of patients on the basis of predominance of one or the other symptom group. The authors discuss implications for the neurobiological underpinnings of negative and positive symptoms.

Adult↗

Dysphoria associated with methylphenidate infusion in borderline personality disorder.

Two patients with borderline personality disorder experienced dramatic dysphoric episodes after acute administration of intravenous methylphenidate in a double-blind manner. These dysphoric episodes were similar to those which occurred spontaneously under conditions of psychological stress. Case histories and the behavioral and cardiovascular effects of the infusions are described. The pharmacology of methylphenidate is discussed in order to elucidate possible mechanisms mediating the observed responses to this drug.

Adult↗

Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients. Correlation with psychosis and response to neuroleptic treatment.

The plasma levels of homovanillic acid (HVA), a major circulating dopamine (DA) metabolite, were measured in schizophrenic patients during five weeks each of double-blind placebo-controlled neuroleptic treatment (N = 16) and withdrawal (N = 11). Both neuroleptic treatment and withdrawal were associated with time-dependent changes in the plasma levels of HVA; treatment was associated with decreases and withdrawal with increases. The levels of plasma HVA measured longitudinally during both conditions were highly correlated with psychosis ratings. Moreover, changes in individual mean weekly levels of plasma HVA were predictive of treatment response, including changes in both positive and negative symptoms of schizophrenia. These data are consistent with the suggestion that the mechanisms of action of antipsychotic drugs involve, in addition to short-term DA receptor blockade, a slowly developing decrease in presynaptic DA activity.

Adult↗

Endogenous opioid regulation of hypothalamo-pituitary-adrenal axis activity in schizophrenia.

We utilized a naloxone challenge strategy to investigate the functioning of the endogenous opioid system (EOS) in schizophrenia. Patients with schizophrenia, who were on neuroleptic medication or drug-free, demonstrated a significantly larger serum cortisol response to opioid blockade by naloxone than did age- and sex-matched normal controls. Patients, but not normal controls, also demonstrated an inverse relationship between baseline cortisol and the magnitude of the response. This enhanced cortisol response is consistent with tonic hyperactivity of the EOS in schizophrenia.

Adult↗