Biomedical subjects

D R Rubinow

Publications and source records attributed to D R Rubinow.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effects of gonadal steroids in women with a history of postpartum depression.

OBJECTIVE: Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression. METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. RESULTS: Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline. CONCLUSIONS: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.

Adult↗

PubMed1999

Cerebrospinal fluid somatostatin, mood, and cognition in multiple sclerosis.

BACKGROUND: Cerebrospinal fluid (CSF) somatostatin (SS) levels have been shown to be decreased in multiple sclerosis (MS) during relapse as well as in disorders characterized by depression or cognitive impairment. Since MS is often associated with depression and cognitive impairment, we examined both the effect of course of illness on CSF SS as well as the variance in SS attributable to associated features (e.g., depression or cognitive impairment). METHODS: Fifteen patients with chronic progressive MS participating in a 2-year cyclosporine trial underwent lumbar punctures for CSF SS at baseline and at 12 and 24 months. Additionally, patients were evaluated by neuropsychological testing, and physical disability and mood ratings. Baseline CSF SS levels were also obtained in a group of control subjects (n = 10). RESULTS: At baseline, CSF SS levels were lower in MS patients than control subjects (p < .001). Decreased CSF SS at 24 months was correlated with decreased cognitive performance on several measures and was best and significantly predicted by cognitive deterioration at 24 months. CONCLUSIONS: Our data support those from previous studies that found lower levels of CSF SS in MS during relapse and suggest that changes in CSF SS are related to the process responsible for diminished cognitive function in MS.

Adult↗

PubMed1999

Dehydroepiandrosterone treatment of midlife dysthymia.

BACKGROUND: This study evaluated the efficacy of the adrenal androgen, dehydroepiandrosterone, in the treatment of midlife-onset dysthymia. METHODS: A double-blind, randomized crossover treatment study was performed as follows: 3 weeks on 90 mg dehydroepiandrosterone, 3 weeks on 450 mg dehydroepiandrosterone, and 6 weeks on placebo. Outcome measures consisted of the following. Cross-sectional self-ratings included the Beck Depression Inventory, and visual analogue symptom scales. Cross-sectional objective ratings included the Hamilton Depression Rating Scale, the Cornell Dysthymia Scale and a cognitive test battery. Seventeen men and women aged 45 to 63 years with midlife-onset dysthymia participated in this study. Response to dehydroepiandrosterone or placebo was defined as a 50% reduction from baseline in either the Hamilton Depression Rating Scale or the Beck Depression Inventory. RESULTS: In 15 patients who completed the study, a robust effect of dehydroepiandrosterone on mood was observed compared with placebo. Sixty percent of the patients responded to dehydroepiandrosterone at the end of the 6-week treatment period compared with 20% on placebo. A significant response was seen after 3 weeks of treatment on 90 mg per day. The symptoms that improved most significantly were anhedonia, loss of energy, lack of motivation, emotional "numbness," sadness, inability to cope, and worry. Dehydroepiandrosterone showed no specific effects on cognitive function or sleep disturbance, although a type II error could not be ruled out. CONCLUSIONS: This pilot study suggests that dehydroepiandrosterone is an effective treatment for midlife-onset dysthymia.

Adaptation, Psychological↗

PubMed1999

The expression of GABA(A) receptor alpha2 subunit is upregulated by testosterone in rat cerebral cortex.

The GABAergic system is sexually dimorphic in certain brain regions and can be regulated by testosterone (T). However, the contribution of T to sex-specific developmental processes in the brain is less clear. We have examined whether T regulates expression of GABA(A) receptor alpha2 subunit in the cerebral cortex of embryonic and postnatal female rats using in situ hybridization and Western blotting. We found that both alpha2 mRNA and protein levels are significantly increased by T treatment at embryonic day 20 (E20) and birth (P0). The observed modulation of the expression of GABA(A) receptor alpha2 subunit by T may be translated into changes in the levels or composition of GABA(A) receptor, either of which would be expected to alter neuronal functional response to GABA activation. As the effects of T are developmental-stage-specific, they may have an organizational impact on brain development.

Analysis of Variance↗

PubMed1999

Conditioned immune response to interferon-gamma in humans.

We determined whether a classical conditioning paradigm may be used to condition immunologic responses in normal human subjects receiving an optimal immunostimulating dose of recombinant human interferon-gamma (rhIFN-gamma). We conducted a placebo-controlled, double-blind study of 31 normal volunteers in order to determine whether an initially immune-neutral stimulus, oral propylene glycol (PG), could eventually elicit an immune response as a consequence of its being paired with a known immunostimulatory dose and schedule of rhIFN-gamma. Subjects were randomly assigned to one of three groups: (A) rhIFN-gamma injections paired with PG; (B) normal saline injections paired with PG; (C) rhIFN-gamma injections alone. During the 4-week study, subjects received progressively fewer injections so that, by the final week of the study, no injections were given and groups A and B received only PG. The principal outcome measures were serum concentrations of quinolinic acid (QUIN) and neopterin, two nonspecific but sensitive markers of immune activation, and expression of Fc receptors (CD64) on peripheral blood mononuclear cells. RhIFN-gamma injections produced significant and predictable alterations in each of the measured immune parameters. No group B subject made an immune response. Mean serum QUIN levels were significantly higher at the end of week three for subjects in the experimental condition (group A) than for subjects receiving rhIFN-gamma alone (group C) despite receiving identical doses of rhIFN-gamma. Similarly, the predicted decay in mean serum neopterin levels from the end of week 1 to the end of week 2 was seen in group C but not in group A. The exposure of group A to PG blunted the decline of CD64 expression in week four. The data suggest that the pairing of an unconditioned stimulus (rhIFN-gamma) and a conditioned stimulus (PG) permits the conditioned stimulus alone to prolong a cytokine-induced response in normal humans.

Adjuvants, Immunologic↗

PubMed1999

Sex differences in expression of serotonin receptors (subtypes 1A and 2A) in rat brain: a possible role of testosterone.

Sexual differences in the expression of messenger RNA and in the binding of serotonin receptors (subtypes 1A and 2A) were studied by in situ hybridization and autoradiography ¿[3H]8-hydroxy-2(di-n-propylamino)tetralin and [3H]ketanserin binding) in the rat brain. Serotonin-1A receptor messenger RNA showed distinct expression patterns for female and male rats. Expression of serotonin-1A receptor messenger RNA was greater in males in subregions of the hypothalamus and amygdala, and less in males in subregions of the hippocampus. No significant differences in the distribution of serotonin-1A receptor binding sites were found between the sexes. Serotonin-2A receptor messenger RNA expression was comparable in males and females in all brain regions except the ventromedial hypothalamic nuclei, where lower levels were seen in females. However, the binding of serotonin-2A receptor measured with [3H]ketanserin was significantly higher in females in all regions of the hippocampus. In a separate study, gonadectomy in males significantly increased serotonin-1A messenger RNA content in the cortex, hypothalamus, hippocampus, amygdala and dorsal raphe, and decreased serotonin-2A messenger RNA in ventromedial hypothalamic nuclei only. Almost all gonadectomy-induced changes were reversed by concomitant administration of testosterone. Our data provide evidence for region-specific sex differences in serotonin receptor subtype 1A and 2A transcription and concentration in the rat brain, and further suggest a modulatory role of testosterone in serotonin (particularly subtype 1A) receptor expression. Gender and gonadal steroid effects on central serotonergic systems may underlie the reported sexual dimorphisms in affective state regulation, response to psychopharmacological agonists or pituitary adrenal activation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

A follow-up study of premenstrual syndrome.

BACKGROUND: Previous data suggest that premenstrual syndrome (PMS) and affective disorder are related. The purpose of this preliminary study was to ascertain (1) whether women with PMS have an increased risk for future major depressive episodes compared with controls and (2) whether PMS is a stable diagnosis over time. METHOD: Patients with prospectively confirmed PMS, along with retrospective DSM-IV premenstrual dysphoric disorder, and asymptomatic controls were studied at 5- to 12-year follow-up using a structured clinical interview. Additionally, those women who still had regular cycles and were medication-free were asked to complete 2 months of prospective daily ratings. RESULTS: Women with PMS (N = 27) had a nonsignificantly higher incidence of new-onset depressive episodes (DSM-III-R and Schedule for Affective Disorders and Schizophrenia-Lifetime Version [SADS-L] criteria) during a 5- to 12-year follow-up compared with controls (N = 21). Differences in incidence disappeared when patients and controls without prior history of depression were compared. Prospective ratings completed during follow-up confirmed original diagnoses of PMS patients (N = 7) and controls (N = 11). CONCLUSION: While preliminary, these results suggest that the higher rate of major depression in patients with PMS during follow-up reflects the higher risk attendant to the history of major depression that existed at baseline. Additionally, at least in a small subsample, PMS appears to be a stable diagnosis over time.

Adult↗

PubMed1998

Estrogen-serotonin interactions: implications for affective regulation.

A burgeoning literature documents the convergence of reproductive endocrine and central serotonergic systems in the regulation of a variety of behaviors. This review will focus on one element of this interaction, the modulation of serotonergic function by estrogen. After describing the manifold neuroregulatory effects of gonadal steroids, we summarize the effects of estrogen on central serotonin systems in animals and humans as inferred from studies demonstrating the impact of gender, estrus (or menstrual) cycle, or hormone manipulation. Finally, we summarize the putative roles of estrogen and serotonin in two reproductive-endocrine-related mood disorders: premenstrual syndrome and perimenopausal depression.

Affect↗

PubMed1998

GABA receptor subunit mRNA expression in brain of conflict, yoked control and control rats.

Animal conflict models have been used for years as a preclinical screen for predicting anxiolytic therapeutic efficacy. Anxiolytics, including benzodiazepines, increase punished responding. This suggests that the punished behavior may be mediated by the GABA receptor. To evaluate this hypothesis, we performed in situ hybridization histochemistry studies of GABA receptor subunits (alpha1-alpha4) and synthetic enzymes glutamic acid decarboxylase (GAD65 and GAD67) in four groups of rats: conflict (punishment), yoked controls (rats shocked without conflict training history), fixed interval only controls (rats that worked for food but were not shocked) and untreated controls. With conflict behavioral training, bilateral reduction of mRNA for the GABAA alpha1 subunit was seen relative to controls in the cortex, thalamus and hippocampus. In contrast, alteration of alpha2 mRNA levels appeared only in the yoked control group, with increased levels seen in the thalamus and cortex and decreased levels in the hippocampus. There were no differences in the alpha2 mRNA level between the control and the conflict behavioral trained animals. Further, no significant differences were found between groups in the mRNA levels for the alpha3 subunit, alpha4 subunit, GAD65, and GAD67. These results suggest that the behaviors related to conflict and uncontrollable aversive stimuli (yoked control group) are accompanied and perhaps mediated by selective changes in the GABAA alpha1 or alpha2 subunits, respectively. These findings highlight the potential usefulness of the conflict model as a means of elucidating the biological underpinnings of anxiety disorder. Published by Elsevier Science B.V. All rights reserved.

Animals↗

PubMed1998

Pituitary-adrenal hormones and testosterone across the menstrual cycle in women with premenstrual syndrome and controls.

BACKGROUND: Premenstrual syndrome (PMS) is a cyclic mood disorder, widely believed, yet not conclusively shown, to be of endocrine etiology. This study examines basal levels of several hormones reported, albeit inconsistently, to differ in women with PMS compared with controls. METHODS: Subjects (10 PMS patients and 10 controls) had their blood drawn for one full menstrual cycle. Subjects' mood and behavioral symptoms were assessed by daily self-ratings and objective ratings. Plasma was assayed for total and free testosterone (T), beta-endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and cortisol. RESULTS: No differences were observed between the PMS and control groups for beta-EP, ACTH, or cortisol. PMS subjects had significantly lower total and free T plasma levels with a blunting of the normal periovulatory peak, a finding that may be epiphenomenal to age. CONCLUSIONS: This study does not confirm previous reports of abnormalities in plasma levels of either ACTH or beta-EP in women with PMS; it also fails to replicate a previous observation of high free T levels in women with PMS. These results are not supportive of a primary endocrine abnormality in PMS patients.

Adrenal Cortex Hormones↗

PubMed1998

Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome.

BACKGROUND: The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome. METHODS: We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales. RESULTS: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration. CONCLUSIONS: In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.

Adult↗

PubMed1998

Hormone measures in reproductive endocrine-related mood disorders: diagnostic issues.

Mood disturbances have been identified in association with changes in levels of reproductive hormones. The use of hormonal measures in the diagnosis of reproductive endocrine-related mood disorders is highly variable, ranging from necessary in perimenopausal depression to irrelevant in premenstrual syndrome. This article describes our view of the use of hormonal measures for diagnostic and research purposes in perimenopausal depression and premenstrual syndrome. We suggest that the understanding of these disorders lies in as yet unidentified contextual factors rather than in hormonal excesses or deficiencies.

Female↗

PubMed1998

Clinical evaluation in studies of perimenopausal women: position paper.

In some women, the perimenopause is associated with the onset of depressive illness, and it is possible that the changes in gonadal steroids accompanying the perimenopause increase an individual's vulnerability to mood destabilization. This article reviews selected aspects of the literature on the relationship between the perimenopause and depression, outlines the evaluation of depression occurring in the context of the perimenopause from a clinical research perspective, and emphasizes methodologic issues to be considered in future studies.

Female↗

PubMed1997

5-HT1A receptor mRNA expressions differ in the embryonic spinal cord of male and female rats.

During critical periods of development, the effects of testosterone (T) on promoting androgenization of the central nervous system (CNS) are reflected not only by behavior, morphology, and hormone secretion but also by gene expression. The mechanisms involved in sexual differentiation of the CNS, however, remain incompletely defined. The current set of experiments examined with in situ hybridization the dimorphism in 5-HT1A receptor mRNA expression in the embryonic rat spinal cord and the possible role of T in the dimorphism. We found sex-related differences in expression of 5-HT1A mRNA in the spinal cord, which were altered by a single injection of T. The results suggest that this gonadal steroid is responsible for the sexual dimorphism in 5-HT1A mRNA expression occurring during the critical period.

Animals↗

PubMed1997

Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women.

There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4-5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.

Adult↗

PubMed1997

Fluoxetine in the treatment of premenstrual dysphoria.

We performed a double-blind, placebo-controlled, crossover trial of fluoxetine in 17 women with prospectively confirmed PMS who also met criteria for premenstrual dysphoric disorder (PMDD). A subset of 10 women with PMDD and an additional 10 controls participated in a single-dose m-chlorophenylpiperazine (m-CPP) challenge during the follicular and luteal phases of the menstrual cycle. We evaluated the ability of the acute behavioral response to luteal phase m-CPP administration to predict therapeutic response to fluoxetine. compared with baseline, fluoxetine, but not placebo, treatment significantly improved both emotional and physical symptoms. We identified 11 (65%) fluoxetine responders who no longer met diagnostic criteria for PMDD during fluoxetine but remained symptomatic during placebo treatment. In addition, acute symptomatic improvement also occurred following m-CPP administration in 7 of 10 women with PMDD. The small number of m-CPP nonresponders did not respond to fluoxetine either. Our findings confirm that fluoxetine is an effective treatment of PMDD.

Adult↗

PubMed1997

The epidemiology of DSM-III-R bipolar I disorder in a general population survey.

BACKGROUND: Data are presented on the general population epidemiology of DSM-III-R bipolar I disorder in the United States. METHODS: Data come from the US National Comorbidity Survey (NCS), a general population survey of DSM-III-R disorders. A modified version of the Composite International Diagnostic Interview was used to make diagnoses. RESULTS: A small (N = 59) clinical reappraisal study showed that the only manic symptom profile that could validly be assessed with the CIDI is characterized by euphoria, grandiosity and the ability to maintain energy without sleep, which described approximately half of all clinically validated bipolar I cases in the NCS. Further analysis focused on this symptom profile, which involved N = 29 cases in the total sample. Lifetime prevalence was estimated to be 0.4% and 12-month prevalence only slightly lower. Caseness was negatively related to income, education and age, positively related to urbanicity, and elevated among the previously married, never married and non-whites. All cases reported at least one other NCS/DSM-III-R disorder and 59.3% reported that their episode of bipolar disorder (either mania or depression) occurred at a later age than at least one other NCS/DSM-III-R disorder. Although 93.2% of lifetime cases reported some lifetime treatment, only 44.7% of recent cases were in treatment. CONCLUSIONS: The type of bipolar disorder examined here is highly chronic, co-morbid and impairing. Increased efforts are required to attract current cases into appropriate treatment. Methodological research is needed to develop more accurate measures of other bipolar symptom profiles for use in general population epidemiological studies.

Age of Onset↗

PubMed1997

The perimenopause and affective disorders.

A variety of epidemiologic studies have identified that the majority of postmenopausal women do not experience a depression during the perimenopause. In contrast, results of several epidemiologic studies and clinic-based surveys suggest that a substantial number of perimenopausal women, in fact, do experience a clinically significant depression. In this article, we review these studies. Case examples are described to introduce a discussion of the characteristics of perimenopause-related depression, and we identify several factors occurring during midlife in women that may potentially contribute to mood dysregulation at this time. Finally, we provide suggestions for the evaluation and management of women presenting with perimenopause-related depression.

Depression↗