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Biomedical subjects

C B Nemeroff

Publications and source records attributed to C B Nemeroff.

At least 19 recordsLinked to original sources
PubMed1992

Cerebrospinal fluid neuropeptides in dementia.

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had equally elevated CSF CRH and TRH but not SRIF levels as compared with the controls. This elevation was, however, not seen in patients with simple dementia while it was most prominent in those exhibiting marked depressive symptoms. It is concluded that depression rather than dementia itself may be associated with CSF CRH and TRH elevation in elderly patients with cognitive impairment.

Aged↗
PubMed1992

Effects of neurotensin on caudate nucleus protein phosphorylation.

The tridecapeptide, neurotensin (NT), is heterogenously distributed in the mammalian central nervous system and exhibits many neurotransmitter-like characteristics. However, the molecular mechanisms of NT signal transduction remain obscure. In this report, we demonstrate NT-induced stimulation of specific protein substrate phosphorylation in the rat caudate nucleus. Rat caudate nucleus was dissected, a P2 fraction prepared and proteins phosphorylated in vitro with [32P]ATP for 1 min. Phosphorylated proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiograms prepared. NT preincubation in the absence of calcium resulted in markedly increased phosphorylation in vitro of proteins with apparent molecular weights of 80,000 and 50,000. These effects were not observed if calcium was present during the NT preincubation period. Both calcium and cAMP enhanced phosphorylation of the 80 kDa protein, but phosphorylation of the 50 kDa protein was responsive only to calcium.

Amino Acid Sequence↗
PubMed1992

Pharmacological specificity of the increase in neurotensin concentrations after antipsychotic drug treatment.

Neurotensin is an endogenous neuropeptide that produces many CNS effects that are similar to the behavioral and physiological alterations seen after administration of antipsychotic drugs to laboratory animals. As previously reported, sub-chronic (3 week) and acute (single injection) treatment with haloperidol (1 mg/kg), a clinically effective antipsychotic drug increases neurotensin concentrations in the nucleus accumbens and the caudate nucleus. In contrast, a tricyclic antidepressant (desipramine, 10 mg/kg), an anxiolytic (chlordiazepoxide, 25 mg/kg) and a histamine H1 receptor antagonist (diphenhydramine, 20 mg/kg) did not alter neurotensin concentrations in these brain regions after sub-chronic or acute treatment. These data demonstrate pharmacologic specificity to the antipsychotic drug-induced increases in regional brain neurotensin concentrations, and support the hypothesis that these changes may contribute to the clinical efficacy of these drugs.

Animals↗
PubMed1992

5 alpha-pregnane-3 alpha, 21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam.

5 alpha-Pregnane-3 alpha,21-diol-20-one (THDOC; 5 mg/kg) and the triazolobenzodiazepine alprazolam (1 mg/kg) attenuated mild stress-induced increases in plasma corticosterone concentrations via GABAergic mechanisms. Unlike alprazolam, THDOC failed to decrease corticotropin-releasing factor (CRF) concentrations in the locus ceruleus. While THDOC may plausibly act via endogenous GABAergic mechanisms to reduce stress-induced endocrine and behavioral responses that are likely mediated in part by CRF neurons, these preliminary findings suggest that, at the dose and time point studied, THDOC does not identically mimic the actions of alprazolam, another drug which potentiates GABAergic activity.

Alprazolam↗
PubMed1992

Adrenal gland enlargement in major depression. A computed tomographic study.

To determine whether the well-documented hyperactivity of the hypothalamic-pituitary-adrenal axis in depressed patients includes adrenal gland hypertrophy, adrenal gland size was evaluated by computed tomography. Assessments consisted of (1) global ratings by two radiologists ignorant of the diagnostic identity of the subjects and (2) calculation of adrenal volume. Of the 38 patients with major depression, 12 were rated as exhibiting adrenal hypertrophy. Adrenal volumes in the depressed patients were significantly increased when compared with those of normal controls. Adrenal gland size was not correlated with dexamethasone suppression test results, patient age, duration of the depressive episode, or depression severity. These results are concordant with the hypothesis that chronic corticotropin hypersecretion in depression results in adrenocortical hypertrophy. Adrenal gland enlargement may be a measure of cumulative lifetime depression.

Adrenal Glands↗
PubMed1992

Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.

A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3 +/- 17 years old) in comparison with 50 age- and gender-matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2 +/- 1.6 cm3) compared with controls (6.2 +/- 1.7 cm3). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression.

Age Factors↗
PubMed1992

Calcium-, calcium/calmodulin-, and calcium/phospholipid-stimulated protein phosphorylation in the rat anterior pituitary.

Calcium-dependent protein phosphorylation may be a critical step in the stimulated secretion of anterior pituitary hormones. We have noted the existence of a number of calcium-calcium/calmodulin-, and calcium/phospholipid-dependent phosphoproteins in the normal rat anterior pituitary. Cell extracts were prepared from anterior pituitary glands of male rats and phosphorylated with [gamma 32P]ATP in the presence or absence of calcium, calmodulin, and phosphatidylserine. The samples were electrophoresed on SDS-PAGE gels, autoradiographs prepared, and phosphate incorporation into specific proteins quantitated with microdensitometry. Calcium alone significantly stimulated the phosphorylation of proteins with molecular weights of 80.0-, 62.0-, 51.0-, 30.5-, and 25.0-kDa. The phosphorylation of 21.5-, 51.0-, and 80.0-kDa MW phosphoproteins was found to be phospholipid dependent. The phosphorylation of 62.0-, 51.0-, 33.0-, 30.5-, and 25.0-kDa MW phosphoproteins was found to be calcium/calmodulin kinase dependent. Calcium/calmodulin also inhibited phosphorylation of the 80.0-kDa phosphoprotein.

Animals↗
PubMed1992

Corticotropin releasing factor (CRF): studies in alcohol preferring and non-preferring rats.

Electroencephalographic (EEG) responses to corticotropin releasing factor (CRF) as well as CRF concentrations in several brain regions were measured in two lines of rats which have been genetically selected for alcohol preferring (P) or non-preferring (NP) behaviors. Fifteen rats were implanted with chronic electrodes and EEG spectra were evaluated following intracerebroventricular (ICV) administration of CRF (0.15 nmol) or saline. P rats demonstrated a significantly increased EEG response to CRF in the theta frequency range (ANOVA: PREF x DRUG 4-6 Hz, P less than 0.03; 6-8 Hz, P less than 0.05) in frontal cortex. A significantly lower concentration of CRF was found in the P rats in hypothalamus (P less than 0.02), amygdala (P less than 0.003), prefrontal cortex (P less than 0.01), and cingulate cortex (P less than 0.02). The finding that P rats had an increased response to exogenously administered CRF, taken together with decreased CRF concentrations, suggests that CRF receptors may be up-regulated in these animals. Differences in the regulation of CRF neurons may contribute to the expression of behavioral preference for ethanol consumption in these rat lines.

Alcohol Drinking↗
PubMed1992

Cerebrospinal fluid neuropeptides in mood disorder and dementia.

Cerebrospinal fluid (CSF) concentrations of immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were measured in female psychiatric inpatients with DSM-III-R diagnoses of major depression, mania, generalized anxiety and somatization disorder. In addition, elderly patients with dementia disorders, with or without concomitant major depression, were also investigated. CSF SRIF was not significantly different among these groups; on the other hand, mean CSF CRH concentrations were significantly higher in major depression and in dementia with depression as compared with neurological controls with no psychiatric disorders. CSF CRH levels in mania, simple dementia, or anxiety or somatization disorder were not significantly different from the controls. Background physical or clinical variables did not account for the differences in CRH concentrations. It is concluded that CSF CRH elevation may be present in some patients with major depression independent of age and an underlying dementia disorder.

Adult↗
PubMed1992

In vivo assessment of pituitary volume with magnetic resonance imaging and systematic stereology: relationship to dexamethasone suppression test results in patients.

The relationship between dexamethasone suppression test (DST) results and in vivo pituitary volume was studied in 24 psychiatric inpatients. The principles of systematic stereology were used to measure pituitary volume from 3-mm contiguous sagittal spin-echo magnetic resonance (MR) images of the brain. There was no correlation between pituitary volume and 3 p.m. or 10 p.m. postdexamethasone (post-DEX) plasma cortisol concentrations. However, when multiple regression analysis was performed to relate pituitary volume to gender, age, and post-DEX plasma cortisol concentrations, there was a significant relationship between pituitary volume and age, gender, and 10 p.m. post-DEX cortisol plasma concentration. This is the first study to demonstrate a method that directly measures, rather than estimates, in vivo pituitary volume. Furthermore, it suggests that activation of the hypothalamic-pituitary-adrenal axis in psychiatric patients, as manifested by elevated post-DEX cortisol concentrations, may influence pituitary volume.

Adult↗
PubMed1992

CSF corticotropin releasing hormone, somatostatin, and thyrotropin releasing hormone in schizophrenia.

Cerebrospinal fluid (CSF) corticotropin releasing hormone (CRH), somatostatin (SRIF), and thyrotropin releasing hormone (TRH) were measured by specific radioimmunoassay methods in 86 patients who met DSM-III-R criteria for schizophrenia or schizophreniform disorder and in 30 neurologic controls. The multivariate CSF peptide concentration was significantly different in patients compared with controls, but none of the individual variable differences reached statistical significance when analyzed separately. There were no significant CSF neuropeptide differences among patients with various schizophrenic subtypes. Neither global severity of illness nor individual symptoms were correlated with CSF neuropeptide concentrations. Although schizophrenic patients showed a pattern of mildly lower SRIF and TRH levels in their CSF, together with a weak tendency for higher CSF CRH values, these peptide changes did not appear to be specifically related to the core features of schizophrenia.

Adolescent↗
PubMed1992

BMY 14802, a potential antipsychotic drug, increases expression of proneurotensin mRNA in the rat striatum.

Treatment with efficacious antipsychotic drugs, such as haloperidol, increases the concentrations of neurotensin (NT) in the nucleus accumbens and caudate nucleus of the rat. The increases in NT content produced by haloperidol have been shown to be associated with an increase in NT biosynthesis as assessed by the level of expression of proNT mRNA. The potential antipsychotic drug and sigma receptor ligand BMY 14802 has been shown to produce increases in the concentrations of NT in the nucleus accumbens and caudate that are similar to those produced by haloperidol with respect to the magnitude of the increases and the time course over which they occur. This study evaluated the effects of BMY 14802 on the expression of proNT mRNA and NT concentration in the rat striatum. Three hours after a single injection of BMY 14802 (35 mg/kg, i.p.) expression of proNT mRNA was significantly increased in the nucleus accumbens and caudate. Labeling was most intense in the dorsal caudate. NT concentrations were unaltered at this time point. Eighteen hours after injection, significant increases in NT concentration in the nucleus accumbens and caudate were detected. At this time, expression of proNT mRNA was substantially reduced compared to 3 h after treatment although labeling of the dorsal and medial caudate was still greater than that observed in controls.

Amino Acid Sequence↗
PubMed1992

Postnatal development of regional binding of corticotropin-releasing factor and adenylate cyclase activity in the rat brain.

1. Corticotropin-releasing factor (CRF) plays a major role in the endocrine, autonomic and behavioral responses to stress. The distribution of CRF and CRF receptors in hypothalamic and extra-hypothalamic brain regions is consistent with its stress-related functions. 2. In most brain regions, CRF acts primarily, if not exclusively, through activation of the adenylate cyclase systems. 3. While previous studies have demonstrated the prenatal presence of CRF receptors, in the early postnatal period the abundance of CRF receptors relative to the magnitude of CRF-stimulated cAMP production suggests that CRF receptors are not fully linked to adenylate cyclase. 4. Because of our interest in the possible involvement of CRF signal transduction in the development of the neonatal stress response, we have examined postnatal development of CRF receptors in relation to adenylate cyclase activity in the rat. 5. CRF binding decreased significantly in the hippocampus and striatum from postnatal days 7-21. Basal adenylate cyclase activity peaked in the second-third week of postnatal life in each brain region. Preliminary studies suggest that early stress can alter the maturation of second messenger systems in the frontal cortex.

Adenylyl Cyclases↗
PubMed1992

RU486 in depression.

RU486 is a synthetic glucocorticoid antagonist. The authors used RU486 to examine the hypothesis that the elevated plasma cortisol and ACTH in patients is due to suprahypophyseal stimulation of the anterior pituitary. Seven patients and matched controls were studied before and after the administration of RU486. RU486 produced an increase in HPA activity in depressed patients. Thus providing support for the hypothesis that there is increased suprahypophyseal stimulation of the anterior pituitary.

Adrenocorticotropic Hormone↗
PubMed1992

CSF corticotropin-releasing hormone and somatostatin in major depression: response to antidepressant treatment and relapse.

Immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were measured in the cerebrospinal fluid (CSF) of 24 female in-patients, suffering from DSM-III-R major depression, both before and after antidepressant treatment. In the total group there were no significant differences between pre- and post-treatment CSF-CRH and SRIF concentrations despite satisfactory clinical improvement in each patient. However, there was a significant post-treatment reduction of the CSF-CRH concentration in the 15 patients who remained depression-free for at least 6 months following treatment, in contrast to the tendency for elevation in those 9 subjects who relapsed within 6 months. CSF-SRIF showed no similar pattern. High, or even increasing, CSF-CRH concentration during antidepressant treatment may indicate lack of normalization of an underlying process in major depression despite symptomatic improvement and predicted early relapse.

Adult↗
PubMed1992

Reduced platelet tritium-labeled imipramine binding sites in women with premenstrual syndrome.

OBJECTIVE: We studied the possible role of serotonergic systems in the cause of premenstrual affective symptoms. STUDY DESIGN: The binding of tritium-labeled imipramine to platelets is thought to parallel central nervous system binding and to indicate serotonergic activity. We measured platelet tritium-labeled imipramine binding sites in the follicular and luteal phases in 12 controls and in 9 women with well-documented late luteal phase dysphoric disorder. In statistical analyses we used repeated measures analysis of variance, with Student-Newman-Keuls and Duncan's one-tailed t tests, and Pearson's r. RESULTS: The values of subjects with late luteal phase dysphoric disorder were lower than those of controls (F [1,39] = 5.13, p = 0.03). Both follicular and luteal phase level were lower in subjects with late luteal phase dysphoric disorder but reached statistical significance only in the follicular phase. CONCLUSION: Lower platelet tritium-labeled imipramine binding in women with late luteal phase dysphoric disorder supports the hypothesis that alteration of central serotonergic systems may contribute to premenstrual dysphoric symptoms.

Adult↗