Elevated Cerebrospinal Fluid Levels of Immunoreactive Corticotropin-Releasing Hormone in Anorexia Nervosa: Relation to State of Nutrition, Adrenal Function, and Intensity of Depression

Kaye, Walter H.; Gwirtsman, Harry E.; George, David T.; Ebert, Michael H.; Jimerson, David C.; Tomai, Thomas P.; Chrousos, George P.; Gold, Philip W.

doi:10.1210/jcem-64-2-203

Cited by 218 publications

(78 citation statements)

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“…In untreated anorexic patients, salivary cortisol was a reliable tool with which to explore the HPA axis, con®rming the existence of major abnormalities (increased daily cortisol secretion and blunted inhibition by low doses of dexamethasone). In accordance with previous reports (5,8,35), these alterations were unrelated to depressive symptoms and BMI values, and were less pronounced in anorexic patients receiving chronic antidepressant drug treatment.…”

Section: Discussionsupporting

confidence: 92%

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol

Putignano

Dubini

Toja

et al. 2001

European Journal of Endocrinology

155

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Objective: To compare salivary, plasma and urinary free cortisol (UFC) measurements in patients with anorexia nervosa, in whom an overdrive of the hypothalamic±pituitary±adrenal (HPA) axis is well established but information on salivary cortisol is lacking, in viscerally obese patients in whom subtle abnormalities of cortisol secretion and metabolism are postulated, and in normal-weight healthy women. Participants and experimental design: Measurement of salivary cortisol offers a convenient way to assess the concentrations of free, biologically active cortisol in plasma in different physiopathological settings. Forty-seven drug-free, newly diagnosed women with active restrictive anorexia nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe central obesity and 63 normal-weight healthy women entered the study. Salivary and blood samples were collected at 0800 h, 1700 h and 2400 h, together with three consecutive 24-h urine specimens for UFC determination. In controls and patients with anorexia nervosa n 83Y salivary and plasma cortisol were also measured after a 1-mg overnight dexamethasone suppression test (DST). In patients with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and depression. Results: Untreated patients with anorexia nervosa showed increased plasma and salivary cortisol and UFC concentrations (all P , 0X001 compared with controls), and decreased cortisol suppression after DST in plasma and saliva (P , 0X0001 and P , 0X005 respectively compared with controls). These alterations were less pronounced, although still statistically signi®cant, in treated patients with anorexia nervosa. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting the participants by group P , 0X0001X However, for plasma cortisol values greater than 500 nmol/l (the corticosteroid-binding globulin saturation point), this parallelism was lost. Taking plasma cortisol as a reference, the level of agreement for postdexamethasone salivary and plasma cortisol was 58.9% among suppressors and 77.8% among nonsuppressors (x 2 test: P , 0X01). Decreased 0800 h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients with anorexia nervosa (P , 0X005 and P , 0X05 respectively compared with controls), and in saliva in severely obese patients (P , 0X05 compared with controls). Depression and anxiety scores were unrelated to cortisol concentrations in any compartment. Conclusions: Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity. With the establishment of more speci®c and widely acceptable cut-off values for dynamic testing, measurement of salivary cortisol could largely replace plasma cortisol measurement.

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Section: Discussionsupporting

confidence: 92%

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol

Putignano

Dubini

Toja

et al. 2001

European Journal of Endocrinology

155

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“…Multiple hormonal disturbances in AN have been well described (26)(27)(28). Very low leptin levels during starvation were documented by several authors (12)(13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 95%

Longitudinal changes of circadian leptin, insulin and cortisol plasma levels and their correlation during refeeding in patients with anorexia nervosa

Herpertz

Albers

Wagner

et al. 2000

European Journal of Endocrinology

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Objective: To study the longitudinal changes in plasma levels of leptin, insulin and cortisol during the transition from the state of starvation to the state of refeeding focussing on diurnal secretion characteristics and their temporal relationships. Design: Leptin, insulin and cortisol were measured every 2 h for 24 h during acute starvation (T1). Sampling was repeated after reaching half the target-body mass index (BMI) (T2) and again at target-BMI (17.5 kg/m 2 ; T3). The temporal relationships between the diurnal secretion patterns were assessed by cross-correlation analysis. Results: Although BMIs at T1 were uniformly low, leptin levels varied widely within a range clearly below normal levels (0.03-1.7 mg/l). With increasing body fat during the course of refeeding, mean leptin levels increased from 0.64 mg/l (range: 0.27-1.73 mg/l) (T1) to 1.61 mg/l (range: 0.36-4.2 mg/l) (T2) and to 3.67 mg/l (range: 0.7-9.8 mg/l) (T3). Circadian leptin secretion patterns showed maximal values uniformly around 0200 h and minimal values around 0800 h at all stages of the study. At all three weight levels, plasma leptin levels were highest between midnight and the early morning hours and lowest around the late morning hours. Refeeding neither profoundly changed secretion patterns of leptin nor did it change the positive, time-delayed relationship between leptin and insulin with increments in insulin secretion preceding those of leptin by 6 h. A temporal relationship between leptin and cortisol could not be demonstrated in the state of semistarvation but emerged after a substantial weight gain; at that time, leptin increases preceded cortisol increases by 8 h. Conclusions: Absolute leptin, insulin and cortisol levels are profoundly changed during starvation in anorectic patients, while refeeding, paralleled by a BMI gain, reverses these changes. During refeeding the relationship between leptin and cortisol changed profoundly, showing no significant correlation in the state of starvation, whereas at T3 after refeeding a strong inverse relationship could be observed. Leptin and insulin did not correlate significantly at any of the three stages studied.

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“…Higher CRF in cerebrospinal fluid (CSF) has been reported in major depression [11][12][13], as well as PTSD [14], Tourette's syndrome [15], anorexia nervosa [16], and suicide [17][18][19][20]. Postmortem studies of suicides report higher pontine [21] and frontal cortical [22] CRF peptide, and lower frontal cortical CRF binding sites [23] and CRF1 mRNA [22].…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

Sullivan

Parsey

Kumar

et al. 2007

Nuclear Medicine and Biology

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Aim-Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [ 11 C]R121920 and [ 11 C]DMP696 in the non-human primate for application in positron emission tomography (PET) studies of CRF1.Methods-PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET.Results-Both [ 11 C]R121920 and [ 11 C]DMP696 distributed rapidly and uniformly throughout brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [ 125 I]Tyr 0 -sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (B max ) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded B max of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K D ) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore B max and K D were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. Conclusion-Neither[ 11 C]R121920 nor [ 11 C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum.

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Elevated Cerebrospinal Fluid Levels of Immunoreactive Corticotropin-Releasing Hormone in Anorexia Nervosa: Relation to State of Nutrition, Adrenal Function, and Intensity of Depression

Cited by 218 publications

References 0 publications

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol

Longitudinal changes of circadian leptin, insulin and cortisol plasma levels and their correlation during refeeding in patients with anorexia nervosa

PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

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