Cerebrospinal Fluid Corticotropin-releasing Hormone Concentrations Research Articles

Lower cerebrospinal fluid CRH concentration in chronic schizophrenia with negative symptoms

Some patients with schizophrenia have impaired hypothalamic-pituitary-adrenal axis function. However, there is a dearth of studies focusing on corticotropin-releasing hormone (CRH) levels in the brains of schizophrenia patients, which motivated us to examine whether cerebrospinal fluid (CSF) CRH concentrations are altered in these patients. We also examined the possible correlation of CSF CRH level with clinical variables such as schizophrenia symptoms and antipsychotic medication. The study population comprised 20 patients with a diagnosis of schizophrenia according to DSM-5 criteria and 25 healthy controls, who underwent lumbar puncture. Most of the patients were treated with antipsychotic drugs and their doses were converted to chlorpromazine (CP) equivalent values. CSF CRH concentrations were measured by an enzyme immunoassay. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). There was a significantly lower CSF CRH concentration in the patients than in the controls (Mann-Whitney U test: p = 0.014). A significantly negative correlation of CSF CRH levels with PANSS negative scores was found in the patients (Spearman's: ρ = −0.58, p = 0.007). However, CSF CRH concentrations were not significantly correlated with the PANSS total (ρ = −0.035, p = 0.89), positive (ρ = 0.25, p = 0.30), or general psychopathology (ρ = 0.13, p = 0.59) scores. No significant correlation was found with CP equivalent values (ρ = 0.00, p = 1.00). In conclusion, we found that the patients with schizophrenia had lower CSF CRH concentrations compared to the controls and that the lower CSF CRH was associated with negative symptoms of the illness. Further studies in a larger sample and in drug-free patients are warranted.

Temporal changes in the cerebrospinal fluid allopregnanolone concentration and hypothalamic-pituitary-adrenal axis activity in sheep during pregnancy and early lactation

Research on pregnant mice and rats indicated that a neurosteroid allopregnanolone (AP) might have a stress-protective effect, decreasing the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Using a sheep model in the present research, we tested a hypothesis that the cerebrospinal fluid (CSF) AP concentration changes during pregnancy and early lactation, keeping in check the secretory activity of the HPA axis. Four-hour-long CSF collections (20 μL/min, from 10:00 to 14:00) from the third brain ventricle were conducted in 8 sheep, every 4 weeks, starting from the 28th day of pregnancy until the 28th day after delivery, to determine AP and corticotropin-releasing hormone (CRH) concentrations. A maximum of 8 samples (every 30 min) were gathered from individual sheep. Each series of CSF collections was accompanied by blood sampling every 10 min, to examine the distribution of mean plasma adrenocorticotropin (ACTH) and cortisol concentrations. Six luteal-phase sheep were used as a control during the period corresponding to the first month of pregnancy. The highest AP concentration was noted in the 5th month of pregnancy compared to these in the 1st and 2nd months (P < 0.01–P < 0.001). A decrease in the CSF AP level occurred in the 1st month of lactation compared to the concentration noted before delivery (P < 0.05). The CSF CRH concentration reached the highest level in the 4th month of pregnancy compared to these in the 1st and 2nd months (P < 0.001). A decrease in the CRH concentration was observed in the 5th month (P < 0.001, vs 4th month) and then in the 1st month of lactation (P < 0.01–P < 0.001, vs other months of pregnancy). A correlation between the CSF AP and CRH concentrations during four months of pregnancy indicated a very strong relationship (r = =0.9946), but it weakened in the 5th month (r = =0.7079). Both plasma ACTH and cortisol concentrations increased from the 1st to the 4th month of pregnancy (P < 0.01–P < 0.001) and then decreased in the 5th month (P < 0.001). The concentrations of these two hormones remained at lowered levels during early lactation. The CSF CRH, as well as plasma ACTH and cortisol levels in control non-pregnant sheep were generally lower (P < 0.001) than the ones noted in mid-pregnancy. In conclusion, the increasing secretory activity of the HPA axis in pregnant sheep is accompanied by an increase in the CSF AP concentration. The protective effect of AP from excess glucocorticoids may be seen during late pregnancy and early lactation.

No acute suppression of cerebrospinal fluid corticotropin-releasing hormone in man by cortisol administration

Corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) is regarded as index of brain endocrine and behavioral functioning. We investigated the acute effects of intravenous cortisol (100mg) vs. placebo on serial CSF CRH in ten healthy men. CSF CRH concentrations were not significantly suppressed by cortisol within 3h. The origin and regulation of CSF CRH need further research.

Effects of trauma-related audiovisual stimulation on cerebrospinal fluid norepinephrine and corticotropin-releasing hormone concentrations in post-traumatic stress disorder

Although elevated concentrations of both corticotropin-releasing hormone (CRH) and norepinephrine are present in the cerebrospinal fluid (CSF) of patients with post-traumatic stress disorder (PTSD), the effects of exposure to traumatic stimuli on these stress-related hormones in CSF are unknown. A randomized, within-subject, controlled, cross-over design was used, in which patients with war-related PTSD underwent 6-h continuous lumbar CSF withdrawal on two occasions per patient (6-9 weeks apart). During one session the patients watched a 1-h film containing combat footage (traumatic film) and in the other a 1-h film on how to oil paint (neutral film). At 10-min intervals, we quantified CRH and norepinephrine in CSF, and ACTH and cortisol in plasma, before, during, and after symptom provocation. Subjective anxiety and mood were monitored using 100-mm visual analog scales. Blood pressure and heart rate were obtained every 10min from a left leg monitor. Eight of 10 patients completed two CSF withdrawal procedures each. A major drop in mood and increases in anxiety and blood pressure occurred during the traumatic relative to the neutral videotape. CSF norepinephrine rose during the traumatic film relative to the neutral videotape; this rise directly correlated with magnitude of mood drop. In contrast, CSF CRH concentrations declined during the trauma-related audiovisual stimulus, both absolutely and relative to the neutral stimulus; the magnitude of CRH decline correlated with degree of subjective worsening of anxiety level and mood. Plasma cortisol concentrations were lower and ACTH levels similar during the stress compared with the neutral videotape. CSF concentrations of the stress hormones norepinephrine and CRH differentially change after exposure to 1h of trauma-related audiovisual stimulation in chronic, combat-related PTSD. While the CSF norepinephrine increase was postulated, the decline in CSF CRH levels is surprising and could be due to audiovisual stress-induced increased uptake of CSF CRH into brain tissue, increased CRH utilization, increased CRH degradation, or to an acute stress-related inhibition or suppression of CRH secretion.

Cerebrospinal fluid corticotropin-releasing hormone levels are elevated in monkeys with patterns of brain activity associated with fearful temperament

Background: Asymmetric patterns of frontal brain activity and brain corticotropin-releasing hormone (CRH) systems have both been separately implicated in the processing of normal and abnormal emotional responses. Previous studies in rhesus monkeys demonstrated that individuals with extreme right frontal asymmetric brain electrical activity have high levels of trait-like fearful behavior and increased plasma cortisol concentrations. Methods: In this study we assessed cerebrospinal fluid (CSF) CRH concentrations in monkeys with extreme left and extreme right frontal brain electrical activity. CSF was repeatedly collected at 4, 8, 14, 40, and 52 months of age. Results: Monkeys with extreme right frontal brain activity had increased CSF CRH concentrations at all ages measured. In addition, individual differences in CSF CRH concentrations were stable from 4 to 52 months of age. Conclusions: These findings suggest that, in primates, the fearful endophenotype is characterized by increased fearful behavior, a specific pattern of frontal electrical activity, increased pituitary–adrenal activity, and increased activity of brain CRH systems. Data from other preclinical studies suggests that the increased brain CRH activity may underlie the behavioral and physiological characteristics of fearful endophenotype.

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence

The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxietylike symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may, at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neuropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF.

Serial cerebrospinal fluid corticotropin-releasing hormone concentrations in healthy and depressed humans.

CRH, a hypothalamic peptide that is the most potent ACTH secretagogue known, also appears to be produced in the cerebral cortex and spinal cord. Depressed patients have blunted responses to exogenous CRH and normal to high concentrations of CRH immunoreactivity in single morning samples of lumbar cerebrospinal fluid (CSF). Although these data suggest that depression may be associated with hypersecretion of CRH, it has also been postulated that central nervous system insufficiency of CRH might have a pathophysiological role in certain depressive syndromes. We continuously sampled lumbar CSF via indwelling subarachnoid catheters from 1100-1700 h and measured CRH at 10-min intervals in depressed patients and normal subjects. A standardized mixed liquid meal was administered at 1300 h. CSF CRH was strikingly reduced in depressed patients compared to normal subjects [4.2 +/- 1.1 pmol/L vs. 13 +/- 2.1 pmol/L (mean +/- SEM), respectively, P less than 0.01 by Wilcoxon test]. CSF CRH concentrations rose progressively during the experiment in both groups, suggesting a diurnal rhythm and, possibly, response to a test meal. CRH had a very brief half-life in CSF (less than 10 min), suggesting that the spinal cord is the origin of CRH in lumbar CSF. The rapid transients in CSF CRH concentration demonstrate that single samples provide very limited information. There were no intraindividual correlations between CSF CRH concentrations and those of either plasma ACTH or cortisol, both of which rose in response to eating. The present data show that impaired central nervous system secretion of CRH can exist during states of severe depression.

Serial cerebrospinal fluid corticotropin-releasing hormone concentrations in healthy and depressed humans

Serial cerebrospinal fluid corticotropin-releasing hormone concentrations in healthy and depressed humans

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.

Suboccipital cerebrospinal fluid and plasma concentrations of corticotropin-releasings hormone and calcitonin gene-related peptide in patients with common migraine

The concentrations of corticotropin-releasing hormone (CRH) and calcitonin gene-related peptide (CGRP) in cerebrospinal fluid (CSF) obtained by suboccipital puncture and in peripheral plasma from patients with common migraine were investigated. There was a significant decrease in the CGRP level in plasma during a migraine attack compared with the levels in a mixed neuropsychiatric group and with the migraine-free period in migraine patients. No alterations were found in the CSF or plasma CRH concentrations during migraine and in an attack-free period. These results exclude the possibility of any significant CRH-induced alteration of the hypothalamic-pituitary axis in migraneous patients and support the suggestion that CGRP has a role in the pathophysiology of migraine.