Corticotropin-releasing Factor Levels Research Articles

A single administration of 2,3,7,8-tetrachlorodibenzo- p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague–Dawley rats were given TCDD (50 µg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 µg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.

Neurobiological mechanisms for opponent motivational processes in addiction

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

Involvement of Corticotrophin-Releasing Factor and Orexin-A in Chronic Migraine and Medication-Overuse Headache: Findings From Cerebrospinal Fluid

The study set out to investigate the role of corticotrophin-releasing factor (CRF) and orexin-A in chronic migraine (CM) and medication-overuse headache (MOH). Twenty-seven patients affected by CM and 30 with MOH were enrolled. Control CSF specimens were obtained from 20 age-matched subjects who underwent lumbar puncture for diagnostic purposes, and in all of them CSF and blood tests excluded central nervous system or systemic diseases. Orexin-A and CRF were determined by radioimmunoassay methods. Significantly higher levels of orexin-A and CRF were found in the CSF of MOH and to a lesser extent in patients with CM compared with control subjects (orexin-A: P < 0.001 and P < 0.02; CRF: P < 0.002 and P < 0.0003). A significant positive correlation was also found between CSF orexin-A values and those of CRF (R = 0.71; P < 0.0008), monthly drug intake group (R = 0.39; P < 0.03) and scores of a self-completion 10-item instrument to measure dependence upon a variety of substances, the Leeds Dependence Questionnaire (LDQ) in the MOH group (R = 0.68; P < 0.0003). The significantly higher orexin-A levels found in CM and MOH can be interpreted as a compensatory response to chronic head pain or, alternatively, as an expression of hypothalamic response to stress due to chronic pain. A potential role for orexin-A in driving drug seeking in MOH patients through activation of stress pathways in the brain can also be hypothesized.

Regulative effects of essential oil from Atractylodes lancea on delayed gastric emptying in stress-induced rats

Gastric motor dysfunction induced by psychological stress results in many symptoms of functional dyspepsia (FD). There are a number of herbal medicines that are reported to improve gastrointestinal motor. However, the mechanisms of considerable herbal medicines are not explicit. In the present study, the effects of an essential oil (EO) extracted from Atractylodes lancea on delayed gastric emptying, gastrointestinal hormone and hypothalamic corticotropin-releasing factor (CRF) abnormalities induced by restraint stress in rats were investigated and the mechanism of the EO is also explored. Oral administration of EO for 7 days did not affect normal gastric emptying, but accelerated delayed gastric emptying induced by restraint stress in rats. The EO significantly increased the levels of motilin (MTL) and gastrin (GAS) and decreased the levels of somatostatin (SS) and CRF. The EO did not modify gastric emptying in vagotomized rats that underwent restraint stress, but antagonized delayed gastric emptying induced by intracisternal injection of CRF. These results suggest that the regulative effects of the EO on delayed gastric emptying are preformed mainly via inhibition of the release of central CRF and activation of vagal pathway, which are also involved in the release of gastrointestinal hormones such as MTL, GAS and SS.

Serotonin, Stress, and Conditioning

Serotonin, Stress, and Conditioning

406: Mechanisms of fetal meconium passage: Anatomical and biochemical localization of CRF-R1 receptors in fetal rat gastrointestinal tract

Hypoxic-stress is a potent stimulator of in utero meconium passage in term human and rat fetuses. Together with known corticotrophin releasing factor (CRF) gastrointestinal (GI) stimulatory effects and elevated CRF levels in hypoxic rat fetuses, we propose that CRF is a key mediator of hypoxia-induced fetal meconium passage. As CRF action is mediated by binding to GI stimulatory R1 receptors, we sought to determine the presence of CRF-R1 in the GI tracts of term rat fetuses by anatomical and biochemical techniques.

Seizure susceptibility and locus ceruleus activation are reduced following environmental enrichment in an animal model of epilepsy

Alterations in the complexity of social and physical housing environments modulate seizure susceptibility in animal models of epilepsy. The studies described here tested the hypothesis that environmental enrichment would delay seizure onset in the epileptic (El) mouse. Neural activation measured via cFos expression, accumulation of the stress neuropeptide corticotropin-releasing factor (CRF), and behavioral seizure susceptibility were quantified in El mice to better understand the mechanisms of ictogenesis. Enrichment housing of El mice from Postnatal Days 21 to 49 produced a 100% decrease in seizure susceptibility relative to El controls. cFos expression increased in the primary motor cortex, locus ceruleus, and hippocampus of El mice relative to ddY controls, an effect attenuated by enrichment housing. CRF levels were elevated by enrichment in the hippocampus of ddY mice only. This study provides evidence that enrichment housing delays the onset of seizure susceptibility in El mice while altering the neuronal and stress-related responses in seizure-associated regions of the El brain.

Effect of acupuncture on anxiety-like behavior during nicotine withdrawal and relevant mechanisms

Acupuncture, likely the most well-known 'alternative' medical treatment, has been shown to have effects in several types of animal model of drug dependence, including nicotine addiction. We investigated the effect of acupuncture on anxiety-like behavior and corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) mRNA expression in the amygdala during nicotine withdrawal. Rats were given repeated nicotine injections (0.1mg/kg s.c., once daily for 7 days) or saline. Acupuncture groups were treated with acupuncture at acupoint HT7 or ST36 during withdrawal. The anxiogenic response was measured at 72h after the termination of nicotine injection using an elevated plus maze. CRF and NPY mRNA levels were also evaluated using reverse transcription polymerase chain reaction (RT-PCR) analysis at this time. Rats undergoing nicotine withdrawal (NW) were less likely to explore the open arms of the plus maze compared with the saline-treated controls. The percentage of open arm entries in the HT7 acupuncture group, but not in the ST36 acupuncture group, was significantly increased compared with the NW group. Consistent with this behavior, CRF mRNA levels in the NW group were increased compared with the control group. CRF mRNA levels in the HT7 acupuncture group were significantly decreased compared with the NW group. However, NPY mRNA levels were not different among the groups. These findings indicate that increases in CRF may be involved in the negative affect state associated with nicotine withdrawal and that acupuncture may attenuate anxiety-like behavior following nicotine withdrawal by modulating CRF in the amygdala.

Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration

Placental corticotropin-releasing factor (CRF) affects myometrial contractility and the secretion of several uterotonins such as prostaglandins (PGs); however, the activity of CRF is counteracted by CRF-binding protein (CRF-BP). At term and pre-term labor, CRF levels in maternal plasma are highest whereas those of CRF-BP are falling, and the cause of this fall is unknown. Thus, in this study, we investigated the effect of PG administration for labor induction on maternal plasma CRF and CRF-BP concentrations. Maternal plasma CRF and CRF-BP levels were assayed before and after (2 h later) induction of labor by intracervical administration of prostaglandin E(2) (PGE(2)), and at delivery in a group of healthy post-term pregnancies (n=18). Controls were women at term out of labor (n=22), who subsequently progressed to deliver a healthy singleton baby. CRF was measured by two-site immunoradiometric assay, and CRF-BP was assayed by radioimmunoassay. Maternal plasma CRF levels were significantly (P<0.0001) lower and CRF-BP significantly (P<0.0005) higher in post-term than in term pregnancies. With respect to induction of labor, 2 mg PGE(2) were sufficient to increase maternal plasma CRF levels at delivery (P<0.005). While 0.5 mg PGE(2) significantly decreased maternal plasma CRF-BP levels at delivery (P<0.001), 2.0 mg PGE(2) significantly reduced CRF-BP concentrations both after 2 h (P<0.05) and at delivery (P<0.0001). In the light of the well-known stimulation of prostaglandin release by CRF, these data suggest a positive feedback effect of PGE(2) on maternal CRF release during induced labor.

CRF 1 Not Glucocorticoid Receptors Mediate Prepulse Inhibition Deficits in Mice Overexpressing CRF

Both corticotropin-releasing factor (CRF) and glucocorticoid receptors (GR) are implicated in the psychotic symptoms of psychiatric disorders. Correspondingly, it is of interest to determine their respective involvement in the sensorimotor gating deficits displayed by transgenic mice overexpressing CRF. These mice reveal lifelong elevations of CRF and corticosterone levels. Effects of the GR antagonists ORG34517 (5-45 mg/kg by mouth [PO]) and mifepristone (5-45 mg/kg PO) and the CRF(1) receptor antagonists CP154,526 (20-80 mg/kg intraperitoneally [IP]) and DMP695 (2.5-40.0 mg/kg IP) on prepulse inhibition (PPI) of the acoustic startle response were studied in mice overexpressing CRF and in their wild-type littermates. In addition, PPI was measured in both genotypes 2 weeks after adrenalectomy with or without exogenous corticosterone administration via subcutaneous pellet implant (20 mg corticosterone). ORG34517 and mifepristone did not influence perturbation of PPI in mice overexpressing CRF; reducing corticosterone levels by adrenalectomy likewise did not improve PPI. Further, elevation in corticosterone levels by pellet implantation did not disrupt PPI in wild-type mice. Conversely, both CRF(1) receptor antagonists, CP154,526 (40-80 mg/kg IP) and DMP695 (40 mg/kg IP), significantly restored PPI in CRF-overexpressing mice. Sustained overactivation of CRF(1) receptors rather than excessive GR receptor stimulation underlies impaired sensorimotor gating in CRF-overexpressing mice. CRF(1) receptors thus may play a role in the expression of psychotic features in stress-related psychiatric disorders.

Early-Life Stress and the Development of Obesity and Insulin Resistance in Juvenile Bonnet Macaques

Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3-5 months of age. Under VFD, food availability is never restricted, and the infant's growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.

Central administration of neuromedin U suppresses food intake in chicks

The appetite-suppressive action of brain-gut peptides is similar in both chickens and mammals. In mammals, the brain-gut peptide neuromedin U (NMU) suppresses food intake via hypothalamic neuropeptides, corticotropin-releasing factor (CRF), oxytocin, and arginine-vasopressin. In chickens, central administration of CRF, oxytocin, or arginine-vasotocin (AVT, a nonmammalian equivalent of arginine-vasopressin) suppresses food intake. However, the anorexigenic action of NMU in chickens has not yet been identified. In the present study, we analyzed the effects of the central administration of NMU on food intake and hypothalamic mRNA levels of CRF, AVT and mesotocin (a nonmammalian equivalent of oxytocin) in chicks. Intracerebroventricular administration of NMU in chicks significantly suppressed food intake and induced wing-flapping behavior. NMU also significantly upregulated mRNA expression of CRF and AVT, but did not influence mRNA expression of mesotocin in the hypothalamus. These results suggest that NMU functions as an appetite-suppressive peptide via CRF and AVT in the central nervous system in chicks.

Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults

Catecholamine-containing projections from the medulla have been implicated in the mediation of activational responses of the paraventricular nucleus of the hypothalamus (PVH) provoked by moderate doses of interleukin-1 (IL-1). To test the generality of this mechanism, rats bearing unilateral transections of aminergic projections were challenged with intravenous IL-1 (2 microg/kg), bacterial lipopolysaccharide (LPS; 0.1, 2.0, or 100 microg/kg), or saline and perfused 3 hours later; their brains were then prepared for quantitative analysis of Fos induction and relative levels of corticotropin-releasing factor (CRF) mRNA. LPS provoked a robust and dose-related increase in Fos expression within the PVH on the intact side of the brain at all doses tested; the response to IL-1 approximated that to the lowest LPS dose. On the lesioned side, Fos induction was significantly reduced at all dosage levels but was eliminated only at the lowest dosage. The percentage reduction was greatest (75%) in IL-1-challenged rats and was progressively less in animals treated with increasing LPS doses (67, 59, and 46%, respectively). Specificity of aminergic involvement was tested by using intra-PVH administration of the axonally transported catecholamine immunotoxin, antiDBH-saporin. This treatment abolished IL-1-induced elevations of Fos-ir and CRF mRNA in the PVH but left intact comparable responses to restraint stress. These data support a specific involvement of ascending catecholaminergic projections in mediating PVH responses to IL-1 and LPS. Residual Fos induction seen in lesioned animals in response to higher doses of LPS provides a basis for probing additional circuits that may be recruited in a hierarchical manner in response to more strenuous or complex immune insults.

Depression-Like Behavior and Stressor-Induced Neuroendocrine Activation in Female Prairie Voles Exposed to Chronic Social Isolation

To assess whether the responses of prairie voles to social stressors play a mechanistic role in the behavioral and physiological changes associated with affective disorders such as depression, as suggested in previous studies. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that share features of social behavior with humans; therefore, they may serve as useful models for examining social behavioral regulations and physiological responses related to depression. In this study, we hypothesized that social isolation in female prairie voles would induce depression-relevant behaviors and alter their neuroendocrine responses to an acute social stressor. Twenty adult female prairie voles were exposed to either 60 days of social isolation or paired (control) housing. They were tested and observed for a depression-like behavior (anhedonia). The levels of corticotropin-releasing factor- and oxytocin-immunoreactive cells in the paraventricular nucleus of the hypothalamus and circulating levels of hormones and peptide were measured in response to an acute social stressor (resident-intruder test). Chronic social isolation produced anhedonia, measured by reduced sucrose intake and sucrose preference relative to the control animals. Compared with the paired animals, the isolated prairie voles displayed increased plasma hormone and peptide levels (oxytocin, arginine vasopressin, and corticosterone) after a 5-minute resident-intruder test, mirrored by an increased number of oxytocin- and corticotropin-releasing factor-immunoreactive cells in the hypothalamic paraventricular nucleus. These findings suggest that isolation in a socially monogamous rodent model induces both behavioral and neuroendocrine changes that are relevant to depression. These results may provide insight into the mechanisms that underlie the development and/or maintenance of depressive disorders in humans.

Elevated Plasma Corticotrophin Release Factor Levels and In Utero Meconium Passage

Intrauterine meconium (MEC) passage and aspiration may result in significant newborn morbidity, though there is little understanding of the physiologic mechanisms for MEC passage. We hypothesized that stress induces fetal MEC passage via corticotrophin releasing factor (CRF), a known mediator of colonic motility in adult rats. Pregnant rats at e22 were subjected to acute hypoxia or normoxia for 35 min, after which rats were anesthetized and fetuses operatively delivered. Amniotic fluid bilirubin and intestinal alkaline phosphatase were measured as markers for MEC passage, and fetal and maternal plasma CRF and corticosterone levels determined. Hypoxic stress induced defecation in all dams and provoked visible MEC passage in all fetuses. Amniotic fluid bilirubin content was significantly higher in hypoxic fetuses versus controls (1.064 +/- 0.101 versus 0.103 +/- 0.003 O.D. at 410 nm) and intestinal alkaline phosphatase was consistently elevated in MEC stained amniotic fluid. Hypoxia significantly increased plasma CRF (maternal, 82 +/- 5 to 196 +/- 14 pg/mL; fetal, 284 +/- 15 to 1523 +/- 185 pg/mL) and corticosterone (maternal, 417 +/- 50 to 1150 +/- 50 ng/mL; fetal, 96 +/- 5 to 182 +/- 10 ng/mL) compared with controls. In view of the known action of CRF in adult colonic motility, these results suggest that hypoxic stress-mediated MEC passage in term fetal rats is mediated by a CRF dependent pathway.

Effect of fluoxetine on depression-induced changes in the expression of vasoactive intestinal polypeptide and corticotrophin releasing factor in rat duodenum

To investigate changes in vasoactive intestinal polypeptide (VIP) and corticotrophin releasing factor (CRF) in the plasma and duodenum of chronic stress-induced depressed rats and the effects of fluoxetine hydrochloride (fluoxetine) treatment on depression-induced changes in VIP and CRF. A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups: control group, saline-treated depressed group, and fluoxetine-treated depressed group. Open-field testing was performed to assess the rats' behavior. VIP and CRF levels in plasma were measured by ELISA. Immunofluorescence techniques combined with laser scanning confocal microscopy (LSCM) were used to investigate VIP and CRF expression in the duodenum. The open-field behavior, both crossing and rearing, of depression model rats, decreased significantly compared with those of normal control rats over 5 min. Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly (fluorescence intensity of duodenal CRF: 11.82 +/- 2.54 vs 25.17 +/- 4.63; plasma CRF: 11.82 +/- 2.54 ng/L vs 25.17 +/- 4.63 ng/L, P < 0.01), whereas duodenal VIP expression and plasma VIP levels decreased significantly (fluorescence intensity of duodenal VIP: 67.37 +/- 18.90 vs 44.51 +/- 16.37; plasma VIP: 67.37 +/- 18.90 ng/L vs 44.51 +/- 16.37 ng/L, P < 0.01). Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats. Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused by chronic stress. VIP is a potential therapeutic strategy.

Mediation of burn-induced hypermetabolism by CRF receptor-2 activity

Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have implicated hypothalamic peptides and receptors of the corticotropin releasing factor (CRF) family as putative mediators of burn-induced hypermetabolism. Increased neuronal activity at the CRF type 2 receptor (CRF R-2) appeared particularly involved in the expression of elevated resting energy expenditure (REE) following major burn trauma. In the present study we continued these investigations of CRF R-2 mediation of burn-induced hypermetabolism, demonstrating that 3rd ventricle injection of CRF R-2 antisense oligodeoxynucleotide (ODN) normalized REE in burned rats. Similar treatments with CRF or CRF R-1 antisense ODNs had no significant effect in burned rats. In addition, 3rd ventricle injection of the selective CRF R-2 antagonist, antisauvagine-30, also reduced REE significantly in burned rats, while similar treatment with the selective CRF R-1 antagonist, antalarmin, was without effect. To determine which endogenous peptide was altered following burn we measured hypothalamic levels of urocortin (UCN) and CRF 15 days after burn injury, finding UCN was significantly elevated by nearly 3-fold, while CRF level tended to be decreased. We also assessed hypothalamic mRNA peptide and receptor expression by real-time PCR 7, 14, and 21 days post-burn, observing decreased CRF expression 7 and 21 days post-burn, decreased UCN-2 expression 7 days post-burn, and no significant alteration in UCN-1 at any time point. However, CRF R-2 mRNA was elevated at each post-burn time point. These results continue to suggest that increased neuronal activity is integrally involved in the mediation of burn-induced hypermetabolism, and that one of the UCN peptides may be the endogenous ligand affecting this receptor.

Behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa L. in the mouse forced swimming test

Curcuma longa L. (turmeric) has been used for centuries in traditional Chinese medicine as a treatment for mental disorders including depression. The studies described here were undertaken to determine the behavioral, neurochemical and neuroendocrine effects of the ethanolic extract from Curcuma longa using the forced swimming test (FST) in male ICR strain of mice. The ethanolic extract was found to reduce the duration of immobility in the mouse FST when orally administered for 21 days. The extract markedly attenuated swim stress-induced decreases in serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine concentrations, as well as increases in serotonin turnover. Furthermore, the ethanolic extract of Curcuma longa significantly reversed the swim stress-induced increases in serum corticotropin-releasing factor and cortisol levels. Under these conditions, the ethanolic extract of Curcuma longa was partly different from fluoxetine and amitriptyline. These results suggested that antidepressant properties of the ethanolic extract of Curcuma longa was mediated through regulations of neurochemical and neuroendocrine systems and it may be a useful agent against depression.

Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26), CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

CSF Corticotropin-Releasing Factor in Personality Disorder: Relationship with Self-Reported Parental Care

This cross-sectional investigation tests the relationship between the level of self-reported childhood parental care and cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentration in adults with and without personality disorder (PD). Based on preclinical models of the lasting effect of post-natal parental care on central CRF function, the primary hypothesis was that childhood parental care, as reflected by the parental bonding inventory (PBI) care and involvement subscale, is inversely correlated with adult CSF CRF levels. The sample includes cerebrospinal fluid CRF samples from 19 subjects who were included in a previously published report on the relationship between CRF level and Childhood Trauma Questionnaire score. Parental bonding was measured retrospectively with the PBI in 54 medication-free male and female subjects, 37 of whom were diagnosed with a DSM-IV PD, 17 of whom were normal controls free of Axis I and II psychopathology. CSF CRF level as measured by lumbar puncture was entered into a model as the dependent variable, with the independent variables of PBI Parental Care and Involvement, diagnostic category, age, and gender. The model predicting CSF CRF level was significant, with PBI parental care and involvement negatively correlated with CSF CRF level. PD subjects with higher than median PBI parental care and involvement score had significantly lower CSF CRF levels than both normal controls and PD subjects with lower than median PBI parental care and involvement. Higher levels of self-report parental care predict lower CSF CRF levels in PD subjects, consistent with a beneficial effect of parental care on decreased stress reactivity, and consistent with previous reports in humans. The cross-sectional design of the study, however, limits causal inferences.