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Biomedical subjects

D R Rubinow

Publications and source records attributed to D R Rubinow.

At least 127 records · Page 7Linked to original sources

Lack of effect of chronic carbamazepine on brain somatostatin in the rat.

We investigated the effects of chronic carbamazepine treatment in rats on brain somatostatin. Following 12 days of carbamazepine treatment, no changes in somatostatin levels were found in any of the brain areas examined which included: amygdala, hippocampus, caudate-putamen, median eminence, arcuate nucleus, nucleus accumbens, nucleus interstitialis of the stria terminalis, nucleus periventricularis, parietal cortex, and occipital cortex. Thus, carbamazepine in low doses does not affect basal levels of brain somatostatin in the rat, in contrast to the previous reports of decreased somatostatin in the cerebrospinal fluid of affectively ill patients.

Animals↗

Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: clinical and theoretical implications.

The pattern and time course of antidepressant response to different treatment modalities provide important clinical information and hints about underlying neurobiological mechanisms. Depressed patients who responded to 1 night's sleep deprivation (11 of 33 patients) showed maximal improvement on day 1 and deterioration in mood thereafter. In contrast, slower onset and more sustained effects were observed following carbamazepine (12 of 37) or electroconvulsive therapy (ECT) (8 of 8). Nearly maximal improvement required about 2 weeks for ECT and 3 weeks for carbamazepine. Possible differential or common biological mechanisms with differential times of action are implied by these data, which are of importance to the neuroscientist attempting to uncover neural substrates of antidepressant response and the clinician attempting to find rapid onset, yet sustained antidepressant treatments.

Carbamazepine↗

Reduced anxiety and depression in cystic acne patients after successful treatment with oral isotretinoin.

We evaluated the psychiatric morbidity and mood characteristics of a group (n = 72) of patients with cystic acne before and after treatment with one of three dosage schedules of isotretinoin. Although no excess psychiatric morbidity was observed, substantial evidence of psychologic distress was noted before treatment. Significant reductions in anxiety were observed on several measures of anxiety after treatment, with mitigation of anxiety and depression most robust in those patients with the greatest dermatologic improvement with isotretinoin.

Acne Vulgaris↗

CSF somatostatin in patients with Alzheimer's disease, older depressed patients, and age-matched control subjects.

Somatostatin-like immunoreactivity was measured in the CSF of 12 patients with Alzheimer's disease, 15 age-matched control subjects, and 20 older depressed subjects. Patients with dementia or depression were found to have lower CSF somatostatin concentrations than control subjects despite markedly different clinical presentations. Severity of depression was clearly different in all three groups but showed no significant correlation with CSF concentration of somatostatin. There was a significant positive correlation between CSF somatostatin-like immunoreactivity and cognitive functioning in all 47 subjects, but this association was not statistically significant within individual diagnostic groups. These data raise interesting questions about possible biological links between Alzheimer's disease and depression in older patients.

Age Factors↗

TSH and prolactin responses to TRH in patients with premenstrual syndrome.

The thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH), administered during the follicular and luteal phases of the menstrual cycle, were examined in 14 women with prospectively confirmed premenstrual syndrome and in nine control subjects. There were no differences in basal or maximum increase in TSH or prolactin values between menstrual cycle phases in patients or in control subjects or between patients and control subjects in either phase. However, there was significantly greater variability in TSH response to TRH among symptomatic patients (seven of 10 patients: three with blunted and four with augmented response) than among control subjects (none of nine patients).

Adult↗

The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells.

STUDY OBJECTIVE: To study the neuropsychiatric manifestations of therapy with interleukin-2 and lymphokine-activated killer cells. DESIGN: Longitudinal survey of consecutive patients who were given the treatment. Each patient was initially interviewed within 5 days before treatment, and a personal and family psychiatric history was obtained during this first session. Cognitive tests and mood self-rating instruments were administered at the beginning and end of interleukin-2 and lymphokine-activated killer cell treatments, before discharge, and at a follow-up visit 2 to 4 weeks after discharge. SETTING: National Cancer Institute inpatient units at the National Institutes of Health. PATIENTS OR OTHER PARTICIPANTS: Sequential samples of 44 patients with metastatic cancer (age range, 28 to 69 years) who were treated systemically with recombinant interleukin-2 combined with autologous lymphokine-activated killer cells between 30 December 1985 and 31 March 1986. MEASUREMENTS AND MAIN RESULTS: Of the 44 patients studied, 15 developed severe behavioral changes that necessitated acute intervention, and 22 patients had severe cognitive changes (all 22 became disoriented and many also had psychometric evidence of cognitive deterioration). The neuropsychiatric side effects were dose and time related, appearing more frequently at the higher dose and almost uniformly at the end of each treatment phase. All 39 patients who were seen at follow-up had a return to their baseline cognitive scores. None of the factors investigated was found to be predictive of the development of neuropsychiatric toxicity. CONCLUSIONS: The development of clinically significant neuropsychiatric changes during the administration of interleukin-2 and lymphokine-activated killer cells was common and may be treatment limiting. A marked latency in the appearance of neuropsychiatric changes after treatment onset was noted in almost all patients. Every patient studied recovered from the neuropsychiatric side effects.

Adult↗

Mood disorders and the menstrual cycle.

Since the premenstrual syndromes characteristically present with mood, cognitive and behavioral disturbances, a special relationship between psychiatric disorders and the premenstrual syndromes has been postulated. With a series of questions we attempted to clarify the nature of the relationship between the menstrual cycle and mood and behavior, and we specifically addressed the similarities and differences between the premenstrual syndromes and formal psychiatric disorders. The premenstrual syndromes may serve as a biobehavioral model for the investigation of the biologic contributors to mood state regulation.

Female↗

CSF somatostatin and abnormal response to dexamethasone administration in schizophrenic and depressed patients.

Low levels of cerebrospinal fluid (CSF) somatostatin and abnormal response to dexamethasone are two neuroendocrine disturbances reported to appear in depression and other neuropsychiatric disorders. We measured the levels of CSF somatostatin in patients with schizophrenia (n = 44) and depression (n = 19). In view of in vitro and animal evidence of the ability of somatostatin to inhibit stimulated corticotropin secretion, we also administered the dexamethasone suppression test to a subgroup of the patients with schizophrenia (n = 16) and the total depressed group. Lower levels of CSF somatostatin were found in dexamethasone nonsuppressors regardless of diagnosis and were negatively correlated with maximum postdexamethasone cortisol level in the total and depressed patient groups. These data suggest a functional relationship between hypothalamic-pituitary-adrenal axis hyperactivity and reduced CSF somatostatin level.

Adult↗

Dopaminergic effects of carbamazepine. Relationship to clinical response in affective illness.

Carbamazepine, a drug used widely to treat epilepsy and trigeminal neuralgia, has been shown to be effective in the acute and prophylactic treatment of manic-depressive illness. While the time course of its antimanic effects parallels that of classic neuroleptics, indirect clinical evidence, such as lack of parkinsonian side effects and tardive dyskinesia, suggests that carbamazepine does not act by blocking dopamine receptors. To assess the effects of carbamazepine on dopamine mechanisms, we measured the dopamine metabolite homovanillic acid (HVA) in the cerebrospinal fluid of affectively ill patients before and after treatment. Carbamazepine did not alter basal concentrations of HVA, but decreased probenecid-induced accumulations of HVA, paralleling results in animal studies. In 25 patients, lower baseline cerebrospinal fluid HVA levels were related to subsequent better acute antidepressive responses to carbamazepine. While the precise mechanism of carbamazepine's effects on dopaminergic systems remains to be determined, this study provides further evidence that carbamazepine does not have a biochemical profile typical of neuroleptics.

Adult↗

Effect of carbamazepine on mean urinary free cortisol excretion in patients with major affective illness.

Carbamazepine, a tricyclic anticonvulsant effective in the treatment of major affective disorder, has been observed to induce cortisol non-suppression following dexamethasone administration. The mechanism of this effect has not been clearly established. In this study, the authors report carbamazepine-induced elevations of mean urinary free cortisol in patients with affective illness. The theoretical and practical implications of these findings are discussed.

Carbamazepine↗

Cerebrospinal fluid somatostatin and psychiatric illness.

Somatostatin is a tetradecapeptide that is assuming increasing importance as a regulator of central nervous system activity. Originally identified as the hypothalamic growth hormone release-inhibiting factor, somatostatin has subsequently been shown to be extensively and selectively distributed throughout the central nervous system, to alter neuron excitability, to regulate and be regulated by the activity of classical neurotransmitters and neuropeptides, to exert a number of direct behavioral actions, and to display neuropsychiatric disorder-related alterations. In this article, a three-part study of cerebral spinal fluid (CSF) somatostatin in affective illness and schizophrenia is presented. In part 1, significant reductions in CSF somatostatin were observed in 49 bipolar and unipolar depressed patients relative to 47 controls. Values during depression were also significantly lower than those observed in affective disorder during the improved state or in schizophrenia. Diurnal studies involving paired AM and PM lumbar punctures revealed that depressed patients and normal volunteers had similar somatostatin values in the evening, despite having significantly different values in the morning. In part 2, the effects of several psychopharmacological agents on CSF somatostatin were examined, particularly the tricyclic anticonvulsant carbamazepine. A significant reduction of CSF somatostatin during treatment with carbamazepine was observed. The effect of carbamazepine on somatostatin could be related to its anticonvulsant, analgesic, or psychotropic effects. Part 3 deals with somatostatin as a major regulator of hypothalamic-pituitary-adrenal (HPA) axis activity. Somatostatin affects HPA activity by inhibiting, at a number of cellular levels, the stimulated release of adrenocorticotrophic hormone (ACTH) from the pituitary. A significant negative relationship between CSF somatostatin and the postdexamethasone plasma cortisol level in 22 depressed and 16 schizophrenic patients was observed. This relationship between low CSF somatostatin and escape from dexamethasone suppression was observed irrespective of diagnosis (i.e., depression or schizophrenia). Thus, there is indirect supporting evidence for a role for somatostatin dysregulation in the most consistently observed biological abnormality in depression, escape from dexamethasone suppression. Further study of somatostatin in neuropsychiatric disorders, and particularly depressive illness, offers great promise for better understanding their underlying affective, vegetative, cognitive, and physiological dysregulations.

Affective Disorders, Psychotic↗

Depression and carcinoma of the pancreas.

A systematic psychiatric evaluation of 21 subjects with intraabdominal malignancy (pancreatic or gastric carcinoma) was performed. Depression was frequently associated with and often the presenting symptom complex of patients with carcinoma of the pancreas. This finding was not observed in patients with gastric carcinoma. Clinical and theoretical implications of these findings are discussed.

Adjustment Disorders↗

Premenstrual changes: a comparison of five populations.

Several studies have suggested that a special relationship exists between premenstrual and major affective disorders. The present report describes the incidence of reported premenstrual symptoms in women with and without prospectively confirmed premenstrual syndrome, women with bipolar or seasonal affective disorder, and controls. The inability of reported symptoms to differentiate women with and without confirmed premenstrual syndrome, as well as the reduced prevalence of reported premenstrual changes in our affective populations relative to previous reports, is discussed.

Adult↗

Different neurotransmitter metabolite concentrations in CSF samples from inpatient and outpatient normal volunteers.

Cerebrospinal fluid concentrations of the neurotransmitter metabolites 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared in two groups of healthy volunteer subjects. One group (outpatient) was composed of 27 subjects who were transported to the outpatient clinic on the day of the lumbar puncture (LP). The other group (inpatient) was composed of 10 subjects who were admitted to the NIMH Research Ward on the evening prior to the LP. After statistical adjustment for age, height, sex and season in which LP was performed the inpatient group had significantly higher concentrations of both 5HIAA and HVA (P less than 0.005 and P less than 0.05, respectively) than the outpatient group. The difference in DOPAC concentration approached significance (P = 0.056), but there was no difference in MHPG concentration between the groups. This result indicates the need for strict control of environment in studies of CSF monoamines and their metabolites.

3,4-Dihydroxyphenylacetic Acid↗