Changes in melatonin levels but not cortisol levels are associated with depression in patients with eating disorders

Disturbances were studied in the nocturnal circadian pattern of serum melatonin and plasma cortisol levels in 33 female patients with an eating disorder (anorexia nervosa, n = 11; bulimia nervosa, n = 12; or both, n = 10) and in ten female control subjects of comparable age. Blood samples were obtained hourly from 8 PM to 6 AM under controlled darkness. Serum melatonin levels in all patient groups were initially similar to those of control subjects. When patients were divided according to depression status, those with concurrent major depression had significantly lower nocturnal melatonin values than the nondepressed group. Weight did not appear to influence melatonin levels. In contrast, all patient groups had significantly higher nocturnal levels of plasma cortisol than control subjects, and neither weight nor depression separated patient groups on profiles of plasma cortisol.     

Serum melatonin and urinary 6-sulfatoxymelatonin in major depression

In this study, serum melatonin and urinary 6-sulfatoxymelatonin (aMT6s) were measured in 14 major depressive inpatients, compared to 14 matched controls according to age, gender, season and hormonal treatment in women. Moreover, the relationship between serum melatonin and urinary aMT6s levels was analysed in the two groups. Results indicated that the two groups of subjects showed a clear melatonin rhythm without significant difference in the mean level of melatonin or aMT6s, in the area under the curve of melatonin or in the melatonin peak. However, the time of the nocturnal melatonin peak secretion was significantly delayed in depressive subjects as compared to healthy controls. Moreover, the depressed patients showed urinary aMT6s concentrations enhanced in the morning compared to night time levels, while these concentrations were lowered from the night to the morning in the control group. These results suggest that the melatonin production is phase-shifted in major depression.     

Bulimia, bulimia-anorexia and nocturnal secretion of melatonin and cortisol

The authors compared nocturnal variations of melatonin (MT) and cortisol levels in subjects with bulimia (n = 12), 6 with a normal body weight and 6 with anorexia nervosa, as well as 6 control subjects. The hypothesis, formulated for anorexia nervosa, that a decrease of noradrenergic activity induces a decrease of pineal activity, therefore a decrease of melatonin secretion, was not confirmed by our study. Moreover, in subjects with bulimia in the absence of anorexia nervosa, no significant decrease of nocturnal melatonin secretion was reported. Significant differences were due to cortisol variations when comparing MTmax/Cmin ratios. Melatonin did not add any complementary biological cue for diagnostic assessment for subjects with eating disorder and depression. The results of this study suggest that melatonin does not appear to be a useful biological marker in bulimia.     

Fatigue mood as an indicator discriminating between anorexia nervosa and bulimia nervosa

In order to clarify the differences in mood states between anorexia and bulimia nervosa, the Profile of Mood States (POMS) with tension-anxiety, depression, anger-hostility, vigour, fatigue and confusion scales was administered to 32 female patients with anorexia nervosa (age range 14 to 32 years, mean age 20 years), 49 female patients with bulimia nervosa (age range 15 to 33 years, mean age 23 years) and 410‘normal’ female subjects (age range 14 to 35 years, mean age 23 years). The scores on the depression, fatigue and confusion scales for both anorexia and bulimia nervosa and those on the tension-anxiety and anger-hostility scales for bulimia nervosa were significantly higher than those for the control subjects. The score on the fatigue scale for bulimia nervosa was significantly higher than that for anorexia nervosa. Moreover, the result of the multiple logistic regression analysis including all of the POMS scales indicated that the fatigue scale significantly discriminated between the two disorders. Fatigue mood appears to be a principal indicator for differentiating between the two disorders.     

Perinatal factors and the risk of developing anorexia nervosa and bulimia nervosa

CONTEXT: Few prospective studies to date have investigated the role of obstetric complications in anorexia nervosa, and no study to our knowledge exists for this in bulimia nervosa. OBJECTIVE: To explore the role of obstetric complications in the development of eating disorders. DESIGN: A blind analysis of the obstetric records of a sample of subjects with anorexia nervosa, with bulimia nervosa, and normal subjects was performed. All of the subjects included in the study belong to the same population birth cohort and were born in the 2 obstetric wards of Padua Hospital, Padua, Italy, between January 17, 1971, and December 30, 1979. SETTINGS AND PARTICIPANTS: Part of the sample of subjects with eating disorders and all of the controls took part in a prevalence study carried out in 2 randomly selected areas of Padua. In addition, all of the subjects with anorexia nervosa and bulimia nervosa of the same birth cohort who were referred to an outpatient specialist unit were included. The final sample comprised 114 subjects with anorexia nervosa, 73 with bulimia nervosa, and 554 control subjects. RESULTS: Several complications, such as maternal anemia (P = .03), diabetes mellitus (P = .04), preeclampsia (P = .02), placental infarction (P = .001), neonatal cardiac problems (P = .007), and hyporeactivity (P = .03), were significant independent predictors of the development of anorexia nervosa. The risk of developing anorexia nervosa increased with the total number of obstetric complications. In addition, an increasing number of complications significantly anticipated the age at onset of anorexia nervosa (P = .03). The obstetric complications significantly associated with bulimia nervosa were the following: placental infarction (P = .10), neonatal hyporeactivity (P = .005), early eating difficulties (P = .02), and a low birth weight for gestational age (P = .009). Being shorter for gestational age significantly differentiated subjects with bulimia nervosa from both those with anorexia nervosa (P = .04) and control subjects (P = .05). CONCLUSIONS: A significantly higher risk of eating disorders was found for subjects with specific types of obstetric complications. An impairment in neurodevelopment could be implicated in the pathogenesis of eating disorders.     

Hypothalamic-pituitary-adrenal-cortical activity in anorexia nervosa and bulimia

We studied hypothalamic-pituitary-adrenal-cortical (HPA) activity in nine underweight women with anorexia nervosa, 12 women of normal body weight with bulimia, and nine control subjects. The measures of HPA activity were the pattern of plasma cortisol secretion over 24 hr and the responses of plasma cortisol to dexamethasone suppression and to low dose ACTH stimulation. The patients with anorexia nervosa had significantly elevated 24 hr concentrations of plasma cortisol compared to the controls and showed significantly less cortisol suppression following dexamethasone. There was no difference between patients with anorexia nervosa and controls in the rise in plasma cortisol following ACTH. On most measures of HPA activity, the normal weight patients with bulimia were indistinguishable from the controls. These results suggest that HPA activity is normal in most patients of normal body weight with bulimia and that the psychological and behavioral disturbances common to both anorexia nervosa and bulimia are, in the absence of significant weight loss, insufficient to produce major alterations in HPA activity.     

Relationship of bone density to estradiol and cortisol in anorexia nervosa and bulimia

Dual photon absorptiometry was used to assess the risk of developing osteoporosis in patients with anorexia nervosa and patients of normal weight with bulimia nervosa. Anorectic patients had significantly lower vertebral bone mineral densities compared with healthy controls. Bulimic patients had values similar to those of controls, and the differences between bulimics and anorectics narrowly missed significance. No significant difference was found between patient groups in measurements of serum estradiol, but anorectics, compared with bulimics, had significantly higher values of 24-hour urinary free cortisol. Hypercortisolemia, by diminishing bone formation and increasing bone resorption, is likely to contribute to the development of osteoporosis in patients with eating disorders.     

Pineal and adrenal function before and after refeeding in anorexia nervosa

Nine female subjects with anorexia nervosa (AN) were studied when emaciated (mean 72% of average body weight), and after refeeding (mean 85% of average body weight). They were compared to 9 individually age-matched female control subjects. On each occasion blood was sampled for serum melatonin and plasma cortisol through the night, and urine was collected over 24 hr to measure sulfatoxy melatonin levels. The AN group did not differ in their level of depression before and after weight gain. There were no significant differences in serum melatonin values among the patient group before or after weight gain and the control group. Levels of urinary sulfatoxy melatonin were also significantly higher in nighttime compared to daytime samples both before and after weight gain. Plasma cortisol values were significantly elevated in the emaciated state and this was accounted for by higher cortisol levels at 9, 10, 11, and 12 PM and at 6 AM compared with the weight restored state and to controls. This study suggests that pineal activity in patients with AN is not altered by chronic changes in weight, and is not closely associated with changes in cortisol.     

Information processing bias in anorexia nervosa

The aim of this study was to investigate preferential information processing style in Eating Disorders (ED). We compared the performance of participants with EDs against healthy controls in a task that measures cognitive style (reflection-impulsivity) and cognitive efficiency (inefficient-efficient). Sixty non-medicated female participants (healthy controls n=26, anorexia nervosa n=20, bulimia nervosa n=14) took part in the Matching Familiar Figures Test (MFFT), a difficult visual search paradigm with high response uncertainty. Participants with anorexia scored significantly higher on the efficiency dimension score than the control group. No significant differences were found across groups on the dimension 'reflection-impulsivity'. Participants with anorexia are more efficient (quicker response latencies in conjunction with fewer errors) in this visual search task that requires an analytic approach. This supports the hypothesis that individuals with anorexia have a positive bias toward local detail processing, indicative of weak central coherence.     

Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes

OBJECTIVE: Lifetime rates of full and partial anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects. METHOD: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered. RESULTS: Whereas anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than anorexia nervosa in female relatives of comparison subjects, but it, too, aggregated in the families of ill probands; the corresponding relative risks for bulimia nervosa were 4.2 and 4.4 for female relatives of anorexic and bulimic probands, respectively. When partial syndromes of anorexia nervosa and bulimia nervosa were considered, relative risks fell by one-half in each group of ill probands. CONCLUSIONS: Both anorexia nervosa and bulimia nervosa are familial. Their cross-transmission in families suggests a common, or shared, familial diathesis. The additional observation that familial aggregation and cross-transmission extend to milder phenotypes suggests the validity of their inclusion in a continuum of familial liability.     

Cardiac regulation in bulimia nervosa

Heart rate and vagal tone were assessed during sleep and bed rest conditions in nine patients with bulimia nervosa (BN), six patients with concomitant anorexia nervosa and bulimia nervosa (AN + BN) and five control subjects. During bed rest conditions AN + BN patients had significantly lower heart rates than BN or control subjects. During sleep, the heart rate differed significantly for all three groups. The AN + BN group had a significantly lower heart rate than either the BN or control groups and the BN group had a significantly lower heart rate than controls. On the other hand, measures of vagal tone, based on respiratory sinus arrhythmia, were significantly elevated in both patient groups compared to controls. These findings suggest that the bradycardia during sleep in BN patients may be primarily due to hypervagal activity, but the greater bradycardia demonstrated in those patients with both AN and BN may result from hypervagal activity coupled with reduced sympathetic activity.     

Risk factors for anorexia nervosa: three integrated case-control comparisons

BACKGROUND: Many risk factors have been implicated in the development of anorexia nervosa. Little is known about their relative contributions, nor in most cases is it clear whether they are specific to anorexia nervosa or risk factors for all eating disorders or for psychiatric disorder in general. METHODS: We used a case-control design involving the comparison of 67 female subjects with a history of anorexia nervosa with 204 healthy control subjects, 102 subjects with other psychiatric disorders, and 102 subjects with bulimia nervosa. A broad range of risk factors was assessed by interview. RESULTS: The subjects with anorexia nervosa and the healthy controls differed in their exposure to most of the putative risk factors. There was no greater exposure to factors that increased the likelihood of dieting, once the influence of other classes of risk factors had been taken into account. Premorbid perfectionism and negative self-evaluation were especially common and more so than among the general psychiatric controls. Parental obesity and an early menarche, together with parental psychiatric disorder, distinguished those with bulimia nervosa from those with anorexia nervosa. CONCLUSIONS: There appears to be a broad range of risk factors for anorexia nervosa and bulimia nervosa, some of which are shared with other psychiatric disorders. Factors that increase the likelihood of dieting seem to have more important influence as risk factors for bulimia nervosa than anorexia nervosa. Perfectionism and negative self-evaluation appear to be particularly common and characteristic antecedents of both eating disorders.     

Melatonin circadian rhythm in anorexia nervosa and obesity

The mean 24-hour secretion and circadian rhythm of melatonin were studied in 12 female subjects with anorexia nervosa (AN), 13 massively obese (OB) women, and 9 normal weight healthy volunteers to investigate the relationship between type of feeding behavior and hormonal secretory pattern. Blood samples for melatonin were drawn every 4 hours from 0400 h to 2400 h and every 2 hours from 2400 h to 0400 h. Mean 24-hour melatonin secretion was significantly higher in AN than in OB patients and controls. Melatonin circadian rhythms were disrupted in 8 of the 12 AN patients and in 9 of the 13 OB subjects, with phase-advanced nocturnal rises, abnormal diurnal peaks, or no nocturnal rises. The population mean cosinor analysis validated the existence of a significant circadian rhythm of the hormone in AN but not in OB subjects. No significant correlation between mean 24-hour secretion or type of circadian alterations and degree of weight deficit or excess was observed. The circadian alterations of melatonin in AN and OB may be linked to impaired secretory tonus of noradrenalin in the central nervous system, possibly unrelated to feeding patterns.     

Insulin-dependent diabetes mellitus: a risk factor in anorexia nervosa or bulimia nervosa? An empirical study of 116 women

A number of recent studies suggest that diabetes mellitus confers a high risk for the development of anorexia nervosa or bulimia nervosa. In order to test this hypothesis, 56 women with IDDM and 60 non-diabetic female controls were studied. All subjects completed the Eating Attitudes Test (EAT), and the Bulimic Investigatory Test, Edinburgh (BITE). The subjects were interviewed in order to obtain clinical and demographic information as well as to determine test validity. The DSM-III-R criteria of anorexia nervosa and bulimia nervosa were used. Four items were removed from the original EAT in order to eliminate possible bias related to IDDM. The results did not support the hypothesis that eating disturbances occur more frequently in IDDM-patients. Six criteria are proposed to improve the methodological standards of future studies in order to facilitate comparison of results.     

Temperament, character and suicide attempts in anorexia nervosa, bulimia nervosa and major depression.

OBJECTIVE: We examined the relation between personality traits as measured by the Temperament and Character Inventory (TCI) and a reported history of suicide attempts in women with anorexia nervosa, bulimia nervosa and major depression. METHOD: We compared the prevalence and severity of suicide attempts in women with anorexia nervosa (n = 68), bulimia nervosa (n = 152) and major depression with no history of an eating disorder (n = 59), and we examined the relation between the TCI scales and suicide attempts. RESULTS: Comparable numbers of women across the three groups had attempted suicide. The temperament dimension of high persistence and the character dimensions of low self-directedness and high self-transcendence were associated with a reported history of suicide attempts. CONCLUSION: Suicide attempts are equally common in women with eating disorders and women with depression. Whether the observed association between temperament and suicide attempts reflects correlates, causal factors or sequelae of suicide attempts is unknown.     

Urinary MHPG in anorexia nervosa patients with and without a concomitant major depressive disorder

Twenty-four hour urinary MHPG excretion was measured in a group of anorexia nervosa patients before and after five weeks of treatment and in matched normal control subjects. A sub-group of anorexia nervosa patients who met research diagnostic criteria (RDC) for a concomitant major depressive disorder (AN-RDC+) was found to have, both initially and after treatment, significantly lower mean urinary MHPG levels than the normal control subjects. In contrast, mean urinary MHPG levels in anorexia nervosa patients who did not meet criteria for major depressive disorder (AN-RDC+) were similar to values in normal controls. Utilising the median value of all urinary MHPG samples as the cut-off point, it was found that significantly more AN-RDC+ patients excreted low MHPG compared with AN-RDC-patients and normal control subjects. The manifestation of a major depressive disorder according to RDC was found to be more important than body size variables in predicting the variance of MHPG. It is suggested that urinary MHPG levels may be useful in discriminating between sub-types of anorexia nervosa patients.     

Salivary gland enlargement and elevated serum amylase in bulimia nervosa.

BACKGROUND: Clinical reports have described salivary gland enlargement in bulimia nervosa, particularly in patients with elevated serum amylase concentration. The goal of the current study was to provide a controlled comparison of salivary gland size in patients with bulimia nervosa and healthy volunteers. METHODS: Subjects included 17 women with bulimia nervosa and 21 healthy female control subjects. Dimensions of the parotid and submandibular salivary glands were estimated by ultrasonography. Blood samples for amylase measurement were obtained after overnight fast. RESULTS: Parotid gland size was enlarged 36% in patients with bulimia nervosa in comparison to control subjects (p < .01). For the patient group, salivary gland size was significantly correlated with frequency of bulimic symptoms and with serum amylase concentration. CONCLUSIONS: These results provide new quantitative data demonstrating increased salivary gland size in bulimia nervosa. Further studies are needed to evaluate factors responsible for salivary gland enlargement and hyperamylasemia in this disorder.     

Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa

The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.     

EEG-monitored sleep in anorexia nervosa and bulimia

We compared the EEG-monitored sleep of 8 women with anorexia nervosa and 16 normal weight women with bulimia to that of 14 normal women. The patients with anorexia nervosa spent less time asleep and spent less of their sleep time in Stage 1. The sleep of the normal weight patients with bulimia was remarkably similar to that of the controls. These data suggest that most patients with anorexia nervosa and bulimia do not exhibit the type of sleep disturbances characteristic of patients with major depressive illness.     

CSF beta-endorphin and dynorphin in bulimia nervosa.

OBJECTIVE: Preclinical and clinical evidence suggests that central opioid dysfunction may play a role in the pathophysiology of the eating disorders. In particular, endogenous opioids are known to regulate feeding behavior, mood, perception, and neuroendocrine function, all of which are disturbed in patients with eating disorders. Although low concentrations of CSF beta-endorphin have been reported in low-weight patients with anorexia nervosa, central opioid activity in normal-weight patients with bulimia nervosa has not been reported. The authors therefore measured CSF concentrations of beta-endorphin and dynorphin in drug-free female patients with DSM-III-R-defined bulimia nervosa and normal comparison subjects. METHOD: After 4 days of a low monoamine diet and overnight bed rest, CSF was obtained (12-26 cc) from 11 women with bulimia and 17 normal comparison subjects (eight women and nine men). RESULTS: The women with bulimia had significantly lower CSF concentrations of beta-endorphin than did the female comparison subjects. However, CSF concentrations of dynorphin were not significantly different in patients and female or male comparison subjects. beta-Endorphin concentrations were inversely correlated with Beck Depression Inventory scores and the depression subscale of the Eating Disorders Inventory. CONCLUSIONS: These data support a role for central opiates in the mediation of the pathophysiology of the signs and symptoms of bulimia nervosa, although it is impossible to rule out the effects of depression on the results.