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R T Rubin

Publications and source records attributed to R T Rubin.

At least 19 recordsLinked to original sources
PubMed1992

Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects.

To ascertain the extent of dysregulation of melatonin secretion in endogenous depression, we measured nocturnal and diurnal serum melatonin concentrations in 38 depressed patients (23 women and 15 men) who had primary, definite endogenous depression according to the Research Diagnostic Criteria and in 38 individually matched normal control subjects. Previous reports have suggested that such patients may have reduced nocturnal melatonin secretion, often in conjunction with increased hypothalamic-pituitary-adrenal cortical axis activity. This has been considered as a possible reflection of reduced noradrenergic activity in depression. Compared with their matched controls, the depressed patients showed a trend toward a significantly elevated average nocturnal melatonin concentration that was accounted for primarily by the 14 premenopausal women--the postmenopausal female and male depressive patients did not differ significantly from their respective controls. The average diurnal melatonin concentration also showed a trend toward being higher in both the female and male depressed patients. The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects. Our findings thus failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin and nocturnal cortisol concentrations in depression. This discrepancy may be related to methodologic differences among studies; our data are in accord with those findings of the one other reported study in which normal controls were individually matched to patients on variables that were known to influence melatonin secretion. Most of the studies, including ours, have been cross-sectional.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography.

We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99m d,l-hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (average r = .48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic form. Compared with their matched controls, the patients with OCD had significantly increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with 133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Neuroendocrine aspects of primary endogenous depression: XII. Receiver operating characteristic and kappa analyses of serum and urine cortisol measures in patients and matched controls.

The majority of studies investigating the diagnostic utility of hypothalamo-pituitary-adrenal (HPA) axis measures in major depression have focused on the dexamethasone (DEX) suppression test (DST). The DST correlates well, but imperfectly, with other measures of HPA activity. Fewer studies have considered the ability of basal cortisol measures to discriminate depressives from non-depressed patients or normal subjects. We used receiver operating characteristic (ROC) analysis to examine the mean 24-hr serum cortisol concentration, our benchmark of basal HPA axis activity, compared to smaller segments of the 24-hr cortisol profile, post-DEX serum cortisol values, and pre- and post-DEX 24-hr urinary free cortisol (UFC) levels in 40 primary endogenous major depressives compared to 40 matched normal control subjects. No statistically significant differences in ROC curves were found between mean 24-hr cortisol and the other cortisol measures. The mean 24-hr, 1300h-1600h, 1600h-1900h, and 16-hr post-DEX serum cortisol concentrations and the post-DEX UFC level all appeared to be comparable estimators of HPA activity. The single 2300h pre-DEX serum cortisol concentration and the pre-DEX 24-hr UFC level performed notably poorer than did the other measures. We additionally calculated kappa statistics to determine the optimally sensitive and specific discriminators of the cortisol measures between the depressives and the normal controls. The 2300h post-DEX serum cortisol measure was optimally sensitive, and the 1500h post-DEX serum cortisol was optimally specific. The 0700h, 1500h, and 2300h post-DEX serum cortisols were very close together as the optimally efficient measures (best combination of sensitivity and specificity).

Adult↗
PubMed1992

Effects of hypothalamic peptides on the aging brain.

The hypothalamic peptide hormones, TRH, LHRH (GnRH), CRH, GHRH, and GHIRH (somatostatin), influence the release of the anterior pituitary hormones, which in turn promote the release of target endocrine gland hormones and other metabolites. These latter compounds feed back to the brain to help control the secretion of the hypothalamic hormones. This is a dynamic interaction that is influenced by the aging process: Most of these hormones systems become less responsive with advancing age, due to decreased function of peptide-containing secretory neurons, a loss of hormone receptor sensitivity, and/or a reduction in the output of the target endocrine glands. That the hypothalamic peptides themselves can influence brain function is supported by the fact that most are found in areas of the brain other than the hypothalamus and that receptors for them exist in these other areas. For example, CRH is contained in a number of central neural systems that can influence behavior, including limbic areas, the hypothalamus, locus coeruleus, median raphé nuclei, and cortical interneurons. CRH has been shown to be anxiogenic in animal models, and its effect can be blocked by CRH receptor antagonists. CRH content in the locus coeruleus is particularly increased by stress and may influence norepinephrine neurotransmitter function in this structure. In aging there is a gradual reduction of the sensitivity of the brain to the negative feedback of corticosteroids, such that CRH secretion becomes somewhat increased under basal conditions. The behavioral effects of this change are unclear, however, as is the influence of stress-related activation of CRH, ACTH, and glucocorticoid secretion on behavior in the elderly. Other hypothalamic peptides have different patterns of change with aging, and some are markedly altered in pathological conditions; for example, in Alzheimer's disease the content of CRH and somatostatin in certain brain areas is decreased. However, whether the changes in hypothalamic peptides precede or follow the pathological behavioral changes, and how they participate in the changes, is still unclear.

Aged↗
PubMed1992

Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia.

OBJECTIVE: The authors' goal was to evaluate the relationship between plasma concentrations of alprazolam and both treatment response and side effects in patients with panic disorder and agoraphobia. METHOD: Ninety-six patients with panic disorder and agoraphobia were treated at three sites in a 6-week, fixed-dose, double-blind, placebo-controlled, dose-response study of 2 mg/day or 6 mg/day of alprazolam. Assessments were made of panic attacks, avoidance behavior, generalized anxiety, and global response. Blood samples were collected throughout the study and analyzed for alprazolam and other benzodiazepines. RESULTS: Patient compliance with the protocol was judged to be good on the basis of plasma concentrations. According to logistic regression analysis, the relationships between plasma alprazolam concentration and response, as reflected by number of panic attacks reported, phobia ratings, physicians' and patients' ratings of global improvement, and the emergence of side effects, were significant. However, there was no significant relationship between plasma alprazolam concentration and the degree of generalized anxiety symptoms. CONCLUSIONS: The authors conclude that plasma concentration of alprazolam is related to treatment response, particularly in panic attacks. The alprazolam concentration associated with treatment response or with emergence of a given side effect varied widely among individuals, highlighting the necessity for individualized dose adjustment to obtain optimal treatment response while minimizing side effects.

Adult↗
PubMed1992

Discontinuation of alprazolam after long-term treatment of panic-related disorders.

Discontinuation of alprazolam after long-term treatment of 142 patients with panic-related disorders was examined in five study sites using a telephone interview. The majority (67%) of patients interviewed discontinued alprazolam for a period of at least 3 days after a gradual dosage reduction schedule over a 4-week period at the end of the long-term treatment study. A marked difference among the study sites in percentages of patients discontinuing therapy with alprazolam suggests that physician intervention played an important role in determining the ability of patients successfully to discontinue use of alprazolam: 90% and 95% of patients ceased therapy at two sites whereas only 21%, 38%, and 66% of patients discontinued therapy at the other three sites. The mean daily dosage for patients who continued using alprazolam decreased from 5.1 mg/day at the end of the long-term segment to 2.7 mg/day at the time of the poststudy interview. This decline indicates a lack of tolerance to the therapeutic effectiveness of alprazolam over an extended period of time.

Adult↗
PubMed1992

A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

Adolescent↗
PubMed1991

Adrenal gland volume determination by computed tomography and magnetic resonance imaging in normal subjects.

To compare the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) for the quantitative determination of adrenal gland size in human subjects, adrenal gland volumes were determined by both techniques in five female and five male, normal, nonstressed adult volunteers. Mean left and right adrenal volumes were slightly larger by CT, and the left adrenal volume was slightly larger than the right by both imaging techniques. Volume determinations by CT and MRI correlated +0.85 and +0.82 for the left and right glands, respectively. Body surface area was highly correlated, and sex moderately correlated, with left and right adrenal volumes by both techniques. Both CT and MRI somewhat overestimated the known volumes of a set of phantoms, CT by an average of 42% and MRI by an average of 20%. The results of this initial study suggest that MRI holds promise as a technique for in vivo adrenal gland measurements, and that the influence of both body surface area and sex should be considered in comparative studies of adrenal size.

Adrenal Glands↗
PubMed1991

Dose-dependent effects of scopolamine on nocturnal growth hormone secretion in normal adult men: relation to delta-sleep changes.

To explore the sensitivity of nocturnal GH secretion to different degrees of cholinergic blockade, we investigated the effects of two doses of the muscarinic receptor antagonist scopolamine (SCOP; 3.0 and 6.0 micrograms/kg, im) and placebo, administered in a randomized fashion at 2300 h on three nights to eight normal male volunteers. Both doses of SCOP produced significant reductions in mean nocturnal GH concentration compared to the effects of the placebo; the higher dose of SCOP reduced GH to a greater degree than the lower dose, but this difference was not statistically significant (mean, 2.3 micrograms/L after 6 micrograms/kg vs. 3.0 micrograms/L after 3 micrograms/kg). Both SCOP doses significantly shifted GH secretion into later portions of the night, with a significantly greater delay observed after the larger dose. Similarly, a significant delay in the time of the GH rise was produced by SCOP. In contrast, the effects of both doses of SCOP on delta-sleep or sleep onset were small. These data confirm earlier reports demonstrating that cholinergic muscarinic input represents a potentially important source of regulation of nocturnal GH release and suggest that the magnitude of the reduction in GH and the extent of delay in the GH rise time may reflect quantitative differences in the degree of cholinergic blockade. These data are in agreement with recent studies suggesting that the timing of GH release need not be associated with delta-sleep per se.

Adult↗
PubMed1990

Basal and haloperidol-stimulated prolactin in neuroleptic-free men with schizophrenia defined by 11 diagnostic systems.

Forty-four male, neuroleptic-free, acutely psychotic patients with at least one diagnosis of schizophrenia among 11 diagnostic systems, and 28 healthy controls, underwent measurement of prolactin (PRL) concentrations before and after intravenous administration of haloperidol (0.5 mg). Basal PRL concentrations were lower in the patients with Research Diagnostic Criteria (RDC) DSM-III, Cloninger, and Taylor and Abrams schizophrenias than in controls. Compared with the controls, the PRL response to haloperidol was lower in the patients with schizophrenia defined by all diagnostic systems except those of Schneider and M. Bleuler. Neither basal nor stimulated PRL concentrations were correlated with positive symptoms, but basal PRL was correlated with the Brief Psychiatric Rating Scale (BPRS) depression-related subscore. This study lends further support for the presence of dopaminergic dysfunction in schizophrenia, and demonstrates the advantages and problems in the use of multidiagnostic psychopathological evaluation to categorize a disorder where there is major disagreement among diagnostic systems.

Acute Disease↗
PubMed1990

Neuroendocrine aspects of primary endogenous depression. X: Serum growth hormone measures in patients and matched control subjects.

To determine the extent of dysregulation of growth hormone (GH) secretion in endogenous depression, we measured nocturnal serum GH concentrations and GH responses to thyrotropin-releasing hormone (TRH, gonadotropin-releasing hormone (LHRH), and dexamethasone administration in 40 Research Diagnostic Criteria primary, definite endogenous depressives and 40 individually matched normal control subjects. Compared with their controls, the patients showed no difference in basal nocturnal GH concentrations or in GH responses to TRH or LHRH. The GH measures were not significantly related to the other endocrine measures reported previously, including dexamethasone suppression test status. None of the diagnostic schemes for endogenous/melancholic depression which we studied was significantly related to the GH measures in the patients. Of the other subject and symptom variables, the mood depression factor of the Hamilton depression scale and the performance difficulty factor of the Beck depression inventory were moderately negatively correlated with the nocturnal GH measures. These findings suggest that, in contrast to the previously reported hypothalamopituitary-adrenal cortical and thyroid axis abnormalities in our patients, GH secretion was relatively normal. Patients with more severe depressed mood and greater difficulty accomplishing tasks did have moderately lower nocturnal GH values.

Adult↗
PubMed1990

Neuroendocrine aspects of primary endogenous depression: IX. Receiver operating characteristic analysis of the dexamethasone suppression index vs. the dexamethasone suppression test in patients and controls.

The dexamethasone suppression index (DSI), which is the product of the postdexamethasone (DEX) serum DEX concentration and the post-DEX serum cortisol concentration, has been suggested to be a more sensitive discriminative test for depression than the standard DEX suppression test (DST). We used receiver operating characteristic (ROC) analysis to examine the DSI, calculated in several ways, versus the standard DST in a sample of 40 endogenous major depressives and 40 matched normal control subjects. The ROC analysis indicated that the DSI offers no advantage over the standard DST, regardless of which criterion values are used to define cortisol nonsuppression. Serum DEX determinations appear to have value primarily as an indicator of the minimum DEX concentration necessary for an accurate DST.

Adult↗
PubMed1989

Specificity of the salivary cortisol dexamethasone suppression test across psychiatric diagnoses.

One hundred forty-eight psychiatric inpatients, 12 outpatients, and 17 normal controls were given the 1.0-mg overnight Dexamethasone Suppression Test (DST), with salivary cortisol concentrations being measured as the dependent variable. Based on the Structured Clinical Interview for DSM-III, the patients were diagnosed as having major depression with melancholia (n = 21), nonmelancholic major depression (n = 50), mania (n = 15), schizophrenia (n = 32), dementia (n = 6), substance dependence/abuse n = 18), and miscellaneous (n = 18). Neither the melancholic major depressives nor the entire group of major depressives had significantly higher salivary cortisol pre- or postdexamethasone as compared with all the other patients combined, nor did the melancholic patients have significantly higher cortisol than the nonmelancholic depressives. The inpatients as a group had significantly higher pre- and postdexamethasone cortisol values than the normal controls; cortisol values for the outpatients were intermediate between these two groups. Illness severity (in the depressives), length of time in hospital before the DST, and medication regimen were all unrelated to DST outcome. Thus, in this study, the salivary cortisol DST showed little clinical utility in discriminating major depressives with and without melancholia from other patients with a broad range of psychiatric diagnoses. The test did distinguish between hospitalized psychiatric patients and normal control subjects and between depressed inpatients and depressed outpatients, indicating that hospitalization-related variables contributed to DST outcome.

Adult↗
PubMed1989

Differential effects of scopolamine on nocturnal cortisol secretion, sleep architecture, and REM latency in normal volunteers: relation to sleep and cortisol abnormalities in depression.

Scopolamine (SCOP) (3.0 mu/kg and 6.0 micrograms/kg) and saline were administered intramuscularly at 11:00 PM to eight normal male volunteers in a randomized design, and the effects on the sleep electroencephalogram (EEG) and nocturnal cortisol secretion (via blood sampling every 15 min) were evaluated. Compared to saline, SCOP produced a significant dose-related delay in rapid eye movement (REM) latency. In contrast, neither dose of SCOP significantly affected nocturnal plasma cortisol concentrations. These results suggest that the central cholinergic system that regulates the onset of REM sleep is more sensitive to dysregulation than the cholinergic system that controls the degree of nocturnal cortisol secretion. If central cholinergic overactivity is responsible for both the REM sleep latency and cortisol abnormalities in depressed patients, then our findings with SCOP might help explain why the incidences of these abnormalities are different.

Adult↗
PubMed1989

Pharmacoendocrinology of major depression.

Major depressives often have abnormalities in the secretion patterns of their anterior pituitary hormones and target endocrine gland hormones. There are changes in both basal hormone secretion and the responses of these hormones to perturbation tests. Considerable work has been done attempting to develop a clinical application for some of these changes as biological state markers of endogenous depression. Prominent among the changes is an overactivity of the hypothalamo-pituitary-adrenocortical (HPA) axis. The dexamethasone suppression test (DST), as a reflection of HPA axis activity, has been the most thoroughly investigated "biological test" in psychiatry to date. Considerably fewer studies have addressed more fundamental issues of HPA axis regulation in depression, such as the relationship between pre-DST cortisol hypersecretion and DST outcome. The next most widely investigated endocrine axis in depression has been the hypothalamo-pituitary-thyroid (HPT) axis. Most studies have dealt with the TSH response to exogenously administered thyrotropin releasing hormone. While blunted TSH responses have been found in depressives compared with normal controls, the frequency of blunted responses in other types of psychiatric patients has made this test marginally useful for differential diagnosis. The reported changes in other hormone axes, for example the blunted growth hormone response to several challenges noted in depressed patients, have not been investigated sufficiently thoroughly to support their general clinical use at present.(ABSTRACT TRUNCATED AT 250 WORDS)

Depressive Disorder↗
PubMed1989

Neuroendocrine aspects of primary endogenous depression. V. Serum prolactin measures in patients and matched control subjects.

To ascertain the extent of dysregulation of prolactin (PRL) secretion in endogenous depression, we determined nocturnal serum PRL concentrations and PRL responses to thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (LHRH), and dexamethasone administration in 40 Research Diagnostic Criteria (RDC) primary, definite endogenous depressives and 40 individually matched normal control subjects. Compared to their matched controls, the patients showed no difference in basal nocturnal PRL concentrations, a marginally significant 20%-25% increase in the PRL response to TRH, and no differences in post-LHRH or postdexamethasone PRL concentrations. In the patients, there was a weak, negative correlation between age and PRL (r = -0.30), but none of the other subject characteristics or specific dimensions of depressive symptomatology were significantly related to the PRL measures. The PRL measures also were unrelated to pre- and postdexamethasone cortisol concentrations and to the thyrotropin (TSH) responses to TRH in both groups of subjects. In contrast to the previously reported hypothalamo-pituitary-adrenal cortical and thyroid axis abnormalities in these patients, our findings suggest that PRL secretion was relatively normal.

Adult↗
PubMed1989

The predictive power of the salivary cortisol dexamethasone suppression test for three-year outcome in major depressive illness.

Seventy patients satisfying DSM-III and Research Diagnostic Criteria for major depression were given a salivary cortisol dexamethasone suppression test, with samples collected at 0700 h, 1500 h and 2300 h after dexamethasone. The patients were classified as nonsuppressors (mean post-dexamethasone salivary cortisol concentration greater than or equal to 2.0 ng/ml, N = 27) and suppressors (mean post-dexamethasone salivary cortisol concentration less than 2.0 ng/ml, N = 43). At 3-yr follow-up there was no difference in illness outcome as assessed by the life table method or by the length of rehospitalisation for several periods after the index episode. In multiple regression and discriminant function analyses, with outcome as the dependent variable (readmitted within 1 yr, readmitted between 1 and 3 yr, not readmitted), the mean post-dexamethasone salivary cortisol concentration was not significantly predictive of outcome.

Adult↗