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Very little is known to which extent severe underweight could affect cytochrome P-450 (CYP) enzyme activity. In this study, 24 patients with anorexia nervosa at two occasions ingested single oral doses of five test drugs known to be metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. A mixed model analysis was used to evaluate the effect of changes in body mass index (BMI) on the metabolic activities of these enzymes. The primary end point was the change in drug/metabolite ratio of each of the test drugs per kg/m 2 change in BMI. With increasing BMI, the metabolic activity of CYP3A4 decreased (change in the CYP3A4 drug/metabolite ratio per unit change in BMI = 0.056; 95% confidence interval [CI] 0.011 to 0.102; P = .017). For CYP1A2, increasing BMI increased the metabolic activity with borderline significance (change in the CYP1A2 drug/metabolite ratio per unit change in BMI = -0.107; CI -0.220 to 0.005; P = .059). For CYP2C9, CYP2C19, and CYP2D6, no significant changes were seen. The clinical impact of these findings for drug treatment in patients with anorexia nervosa and other severely underweight patients needs to be further studied by examining the pharmacokinetics of specific drugs. This might be particularly relevant for drugs metabolized by CYP1A2 and/or CYP3A4., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Soluble epoxide hydrolase (sEH) converts several FFA epoxides to corresponding diols. As many as 15 FFA epoxide-diol ratios are measured to infer sEH activity from their ratios. Using previous data, we assessed if individual epoxide-diol ratios all behave similarly to reflect changes in sEH activity, and whether analyzing these ratios together increases the power to detect changes in in-vivo sEH activity. We demonstrated that epoxide-diol ratios correlated strongly with each other (P < 0.05), suggesting these ratios all reflect changes in sEH activity. Furthermore, we developed a modeling approach to analyze all epoxide-diol ratios simultaneously to infer global sEH activity, named SAMI (Simultaneous Analysis of Multiple Indices). SAMI improved power in detecting changes in sEH activity in animals and humans when compared to individual ratio estimates. Thus, we introduce a new powerful method to infer sEH activity by combining metabolomic determination and simultaneous analysis of all measurable epoxide-diol pairs., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose in connection with the manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective of this study was to investigate the relationship between methylation patterns of the histone deacetylase 4 gene and eating disorders in a site previously associated with anorexia nervosa (AN). Women with AN (N=28) or bulimia nervosa (BN) (N=19) were age-matched and sex-matched to controls (N=45). We obtained saliva-derived DNA and use bisulfite pyrosequencing to examine region-specific methylation differences between cases and controls. The region assayed includes 15 CpGs. We found no significant association between the previously implicated CpG and either AN or BN. We found that three CpGs were nominally associated with AN (P=0.02-0.03); the largest difference was a 9% hypermethylation in AN. One CpG was nominally associated with BN (P=0.04), with 4% hypomethylation. None of these results remained significant after correction for multiple testing. We did not replicate previous findings, though through expanded coverage, we identified additional CpGs that were nominally associated with eating disorders.

Objective: In patients with anorexia nervosa (AN) specific signs may occur in the oral cavity, but there are conflicting reports about their significance, especially concerning changes in salivary composition. The aim of this clinical study was to evaluate the resting parotid flow rate (PFR) and the activity of the following enzymes in parotid saliva: amylase, aspartate amino transferase (AST), lysozyme, peroxidase, serine and acidic proteases in the acute phase of the restrictive type of AN and to compare the findings with those in healthy controls., Design: Forty-one subjects participated (20 patients with AN, 21 matched healthy controls), parotid saliva was collected using a modified Lashley cap at rest. Enzyme activities were measured with fluorimetric and photometric assays., Results: The unstimulated PFR was significantly lower than in the controls, lysozyme and AST activity was significantly lower, and amylase showed a high inter-individual variability. A positive correlation for amylase and lysozyme and negative ones for lysozyme and BMI, lysozyme and IBW%, serine protease and salivary flow were observed., Conclusions: The reduced PFR and enzyme activities levels suggest that AN does not only affect the quantity of the saliva but also its quality and, its biological functions. The results obtained should help to provide a better understanding of the effect of AN disease on the pathogenesis of at least some oral diseases. Further research is needed on any possible role of reduced lysozyme and transaminase activity in maintaining oral protection against external toxic agents and bacteria., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aminotransferase elevations have been described in patients with anorexia nervosa. Hypothesized etiologies have included ischemic hepatitis, refeeding-induced transaminitis, and the process of autophagy. Supervised enteral nutrition is the mainstay of treatment for severe anorexia, but an increase in aminotransferase levels after initiation of enteral feeding presents clinicians with a diagnostic dilemma. We present a 31-year-old woman with anorexia nervosa (body mass index [BMI] of 13.5 kg/m 2 ) who experienced a worsening of aminotransferase elevations even after the initiation of enteral feeding. Despite nutritional supplementation, the patient's weight continued to fall for 6 days. Peak aminotransferase concentrations correlated with the patient's lowest weight and improved only after an increase in BMI was eventually achieved. Secondary causes of severe transaminitis were investigated, and after no cause was found, a liver biopsy was performed. Pathology was consistent with liver injury secondary to severe malnutrition rather than from refeeding syndrome. This case highlights malnutrition as an important cause of aminotransferase elevations and underscores the need for judicious early weight restoration in patients with anorexia and abnormal liver chemistry.

Individuals with anorexia nervosa (AN) restrict eating and become emaciated. They tend to have an aversion to foods rich in fat. Because epoxide hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared with controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment.

Objective: Evaluation of liver dysfunction in patients with severe anorexia nervosa (AN) has typically been limited to small case series. We report an investigation into the admission characteristics and clinical outcomes associated with liver dysfunction in a large cohort of adults hospitalized for medical stabilization of severe AN., Methods: We retrospectively evaluated electronic medical records to quantify the cumulative incidence of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT). We compared mean (±SD), frequencies (%), and median (IQR) values of clinical covariates of interest by incidence of liver enzyme elevation. The study included 181 adults, admitted for medical stabilization of AN, from October 1, 2008 to December 31, 2013., Results: AST and ALT were mildly elevated in 27.6% of patients and severely elevated (more than three times the upper limit of normal) in 35.4% of patients. On admission, patients with severely elevated liver enzymes had a lower body mass index (BMI) (11.9 ± 1.8 kg/m(2) vs.13.3 ± 1.7 kg/m(2)), lower percentage ideal body weight (56.5% ± 7.7% vs. 63.5% ± 8.3%), and lower prealbumin (64% vs. 37%) compared with the rest of the cohort (p < 0.001). While hospitalized, patients with severely elevated liver enzymes more often developed hypoglycemia, hypophosphatemia, and experienced longer lengths of stay (p < 0.001)., Discussion: Elevated liver enzymes are common in our patient population with severe AN. Liver enzymes reached near normal values by the time of discharge. Severely elevated liver enzymes were associated with a lower BMI and the development of hypoglycemia., (© 2015 Wiley Periodicals, Inc.)

Objectives: Patients with anorexia nervosa are at high risk for general and oral diseases. However, not all anorexic patients suffer from them, irrespective of the severity of their eating disorder. It is often speculated that differences in the saliva are important; however, little is known about salivary parameters in anorexic patients. The aim of the clinical trial was to evaluate stimulated and resting salivary flow rate and the activity of the following enzymes in both types of saliva: amylase, aspartate amino transferase (AST), alanine amino transferase (ALT), collagenase, lysozyme, peroxidase, serine and acidic proteases, and trypsin in persons with anorexia nervosa (AN) and to compare them with those of healthy controls., Materials and Methods: Sixty-six subjects participated (28 patients with anorexia nervosa, 38 matched healthy controls)., Results: Regarding flow rate, stimulated and unstimulated levels were significantly lower in the AN group than in the controls. Activities of collagenase and AST in stimulated saliva were significantly higher in anorexic participants. In the AN group, changes due to salivary stimulation were found for the activity of acidic proteases, AST, and lysozyme., Conclusion: Reduced salivary flow might be one indicator of anorexia. Despite starvation and anorexia development, salivary key enzymes show physiological activity. This indicates a partial adaptation of the organism to severe condition during malnutrition., Clinical Relevance: Further research is needed into possible role of reduced collagenase and transaminase activities in maintaining protection against external noxae and bacteria which might have impact on general oral health among patients with anorexia nervosa.

Background & Aims: Aminotransferase abnormalities have been reported in malnourished patients with anorexia nervosa (AN). The aim of this study was to identify prevalence and risk factors of hyperaminotransferasemia in an adult cohort of AN patients and to describe evolution during nutritional rehabilitation with enteral nutrition for a period of 4 weeks., Methods: Retrospective study of all consecutive malnourished (BMI <16) AN adult patients, without previous liver diseases or hepatotoxic drugs or alcohol consumption, hospitalized for enteral nutrition in a single center between 1998 and 2008. Hypertransaminasemia was defined by an increase in AST and (or) ALT >2N., Results: In all, 126 AN patients (117 W, 9 M), age 30 ± 10.8 years, were included. At admission, 54 (43%) patients presented hypertransaminasemia. In univariate analysis, risk factors for hypertransaminasemia were: lower BMI (11.2 ± 2 vs. 13 ± 2, p < 0.0001) and age (28 ± 9 vs. 32 ± 12, p < 0.05), male sex (p < 0.05) and the pure restrictive form (p = 0.07). In multivariate analysis only BMI, at a threshold of 12, remained significant [OR 3.7, CI: 95% 2.24-5.2]. Normalization of aminotransferases at the end of week 4 of enteral nutrition was obtained in 96%. Only 2/54 patients (4%) presented a worsening of aminotransferases during the refeeding period, including one that died of liver failure. None of the patients without hypertransaminasemia admission presented a subsequent elevation. At the end of the 4-week refeeding period, the increase in BMI was greater in patients without hypertransaminasemia than in those with it (2.0 ± 0.8 vs. 1.5 ± 1.0, p < 0.0001)., Conclusion: Elevated transaminases is common in severe malnourished AN patients. Four risk factors were identified: young age, low BMI (the only independent factor in multivariate analysis), the pure restrictive form of the disease and male sex. After 4 weeks of enteral nutrition the evolution is in most cases favourable, albeit with a lower increase in BMI, but can be severe. The long-term evolution remains to be determined., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Previous studies have shown relationships between personality styles and markers of serotonergic functioning, but data on patients with anorexia nervosa (AN) are scarce., Methods: The personality styles and disorder inventory was administered to 47 acute patients with anorexia nervosa (acAN), 27 weight-recovered patients (recAN) and 72 healthy controls (HC) aged between 14 and 21 years. Platelet monoamine oxidase (MAO-B) activity was assayed with [14C]-β-phenylethylamine as substrate., Results: AcAN had significant elevated scores on 9 of the 14 personality style subscales when compared to HC, whereas recAN were largely normal. Platelet MAO-B activity and "ambitious/narcissistic" scores correlated negatively in acAN. In recAN we found positive correlations between MAO-B and personality subscores., Conclusions: The inverse relationship between a cluster B personality style and MAO-B activity in acAN is in accordance with studies in other patient populations. In contrast, positive associations between problematic personality styles and MAO-B activity in recAN combined with the overall decreased MAO-B activity in this group adds to the existing evidence suggesting a general dysfunction of the serotonergic system as a trait marker for AN., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: The evidence that the activity of the sympathetic nervous system (SNS) is decreased in acute anorexia nervosa (AN) is not consistent. Therefore, we aimed to assess the SNS basal activity in malnourished AN patients through the measurement of diurnal salivary levels of α-amylase, whose secretion is regulated by the SNS. As secondary aim, we measured also salivary cortisol., Methods: Eight symptomatic female patients with restrictive AN and eight age-matched healthy women underwent saliva sample collection at awakening and over the day. α-amylase and cortisol were assayed by ELISA method., Results: In both patients and controls, saliva α-amylase levels significantly decreased during 60 min after awakening and then progressively rose towards the afternoon/evening. AN patients exhibited significantly reduced levels of the salivary enzyme with a significant decrease in its overall diurnal secretion and a dysregulated secretory pattern. As compared to control women, AN patients exhibited significantly enhanced levels of salivary cortisol at awakening, an enhanced and advanced cortisol secretion after awakening but no significant change in the overall diurnal secretion of the salivary hormone., Conclusions: These results suggest that the activity of the SNS, evaluated through the assessment of the diurnal secretion of salivary α-amylase, is impaired in the acute phase of AN whereas the cortisol awakening response is enhanced., (© 2011 Informa Healthcare)

Introduction: Central serotonergic pathways may play an important role in the etiology of anorexia nervosa (AN). Although platelet monoamine oxidase activity (MAO-B) has been proposed as an index of cerebral serotonin activity, studies in patients with AN are scarce., Methods: Platelet MAO-B activity was determined in 59 acutely underweight AN patients (acAN, aged 14-29 years, BMI=15.2+/-1.4), 35 weight-recovered AN patients (recAN, aged 15-29, BMI=20.8+/-2.2) and 59 healthy control women (HCW, aged 14-26, BMI=21.6+/-2.1). Plasma leptin served as an indicator of malnutrition. Results were compared by ANCOVA controlling for confounding variables., Results: Platelet MAO-B activity in acAN patients (5.2+/-1.4 nmol/10 (9)pltx15 min) was similar to HCW (5.5+/-1.9) but significantly lower in recAN patients (4.4+/-1.5). BMI and leptin showed a significant negative correlation with MAO-B activity in AN patients, but not in HCW., Discussion: Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Whether low MAO-B activity in weight-recovered AN patients indicates a premorbid trait or a secondary change due to recovery remains to be elucidated.

Objective: To determine the prevalence and predictors of abnormal liver enzyme levels in ambulatory young women with anorexia nervosa (AN)., Study Design: In this cross-sectional study of 53 females with AN, serum concentrations of liver enzymes and hormones were measured. Anthropometric, dietary, and body composition information was collected. Correlational analyses were performed between liver enzyme concentrations and these variables., Results: Elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels were found in 14 subjects (26%) and 5 subjects (9%), respectively. ALT and GGT were inversely correlated with body mass index (r = -0.27 to -0.30, P < .049) and percentage body fat (r = -0.36 to -0.47, P < .007) but showed no relationship with lean body mass. Subjects with percentage body fat < 18% had higher ALT levels than those above this threshold (median 26.5 vs 18.0 U/L, P = .01). Liver enzyme concentrations did not correlate with dietary variables, except for GGT and percentage of calories from protein (r = 0.28, P = .04)., Conclusions: Serum ALT and GGT concentrations are inversely related to adiposity in young women with AN. Future studies are needed to determine whether these liver enzyme elevations signify unrecognized, clinically relevant liver disease.

Objective: Several lines of evidence suggest that alterations in serotonergic activity contribute to the pathophysiology of abnormal eating behaviors. Since platelet monoamine oxidase (MAO) activity and the 5-HT transporter gene promoter polymorphism (5-HTTLPR) have been associated with eating disorders, the knowledge from a population-based sample may provide useful information which changes in 5-HT function observed in eating disorders represent trait vs. state effects., Method: The sample was based on both cohorts of the Estonian Children Personality, Behavior and Health Study (ECPBHS). The current study was conducted during the second follow-up where altogether 82% from the original sample was recruited. EDI-2 subscales--Drive for Thinness and Bulimia--were used to determine eating attitudes and behaviors. Platelet MAO activity was measured and the participants were genotyped for the 5-HTTLPR., Results: Allelic variation of 5-HTTLPR or platelet MAO activity were not independently associated with drive for thinness or binge eating, but girls homozygous for the 5-HTTLPR long allele and with high platelet MAO activity, both considered indicators of a higher capacity 5-HT system, exhibited higher scores of drive for thinness., Conclusion: The results suggest that drive for thinness is the highest in girls with the presence of two markers of higher serotonergic capacity., ((c) 2008 by Wiley Periodicals, Inc.)

Objective: The present study aimed to evaluate serum liver enzymes in underweight outpatients with anorexia nervosa (A-NERV) or eating disorders not otherwise specified (EDNOS)., Method: Serum alanine amino transferase (ALT), aspartate amino transferase (AST), lactic dehydrogenase (LDH), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and cholinesterase (CHE) were determined in 97 patients with A-NERV, 66 patients with EDNOS, and 56 controls., Results: In the A-NERV group AST, LDH, and GGT were higher, as compared with controls, and inversely related to weight, while ALP and CHE were lower. AST and GGT increased and CHE decreased in patients with EDNOS. Hypertransaminasemia occurred in 14.4 and 15.2%, and low CHE in 29.9% of the A-NERV group and 13.6% and EDNOS group, respectively. Three or more abnormalities were found in 9.3% of patients with A-NERV and 7.5% of those with EDNOS., Conclusion: Abnormalities in serum liver enzymes are common in outpatients with eating disorders plus underweight. CHE might be considered as a marker of the effects of primary malnutrition on liver function., ((c) 2007 by Wiley Periodicals, Inc.)

Anorexia nervosa (AN) is a severe and complex psychiatric disorder with a significant genetic contribution. Previously, we found an association between AN and the 158Val/Met polymorphism of the catechol-O-methyltransferase (COMT) gene in a family-based study of 51 Israeli AN trios. In the present study, we extended the original sample to include 85 family trios [66 AN restricting (AN-R) and 19 bingeing/purging (AN-BP) subtype] and performed a family-based transmission disequilibrium test (TDT) analysis for five SNPs in the COMT and two in the adjacent ARVCF gene. Association was found between AN-R and several SNPs in the COMT-ARVCF region including the 158Val/Met polymorphism. TDT analysis of 5-SNP haplotypes in AN-R trios revealed an overall statistically significant transmission disequilibrium (P < 0.001). Specifically, haplotype B [COMT-186C-408G-472G(158Val)-ARVCF-659C(220Pro)-524T(175Val)] was preferentially transmitted (P < 0.001) from parents of AN-R patients to their affected daughters, while haplotype A [COMT-186T-408C-472A(158Met)-ARVCF-659T(220Leu)-524C(175Ala)] was preferentially (P = 0.01) not transmitted. Haplotype B was associated with increased risk (RR 3.38; 0.95CI 1.98-6.43) while haplotype A exhibited a protective effect (RR 0.40; 0.95CI 0.21-0.70) for AN-R. Preferential transmission of the risk alleles and haplotypes from the parents was mostly contributed by the fathers. No significant transmission disequilibrium of alleles or haplotypes was found for AN-BP trios. The risk and protective haplotypes may carry molecular variations in the COMT gene or its vicinity that are relevant to the pathophysiology of restrictive anorexia nervosa in the Israeli-Jewish population., ((c) 2005 Wiley-Liss, Inc.)

The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol-O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent family trio-based study of patients from Israel. In an attempt to replicate this finding, we performed a combined family trio and case-control study in an European population from seven centers in six different countries (Austria, Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain), together contributing a total of 372 family trios, 684 controls and 266 cases. TDT analyses of high (H) and low (L) alleles in family trios showed that H allele and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case-control analysis using separate samples simply combined from the centers was also not significant, with the frequencies of the H allele 50% in cases and same in controls. Stratified analysis of data from all centers gave an odds ratio of 0.98 (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise not significant (overall chi(2) = 0.42). Because we were not able to support the primary hypothesis that Val158Met is a risk factor for AN, we did not perform secondary analysis of minimum body mass index (mBMI), age at onset or illness subtype (restricting or binge purging anorexia). Overall we found no support for the hypothesis that the Val158 allele of COMT gene is associated with AN in our combined European sample., (Copyright 2003 Wiley-Liss, Inc.)

Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, has been postulated to modulate nutrition control by modification or inactivation of peptide hormones operating in the enteroinsular axis. We hypothesized that changes of DPP IV activity in serum are related to the nutrition status of patients with eating disorders. Serum DPP IV activity was measured in 52 patients (28 with anorexia nervosa and 24 with bulimia nervosa) in four consecutive weekly analyses. Simultaneously, the number of CD26 (DPP IV)-positive peripheral blood lymphocytes was counted. The same analyses were carried out in 28 healthy female volunteers. In week 1 and throughout the observation period, DPP IV activity in the sera of patients with anorexia nervosa and, to a lesser extent, those with bulimia nervosa was elevated in comparison to that of healthy controls (week 1: means = 92.8 U/L for anorexia-nervosa patients and 89.3 U/L for bulimia-nervosa patients versus 74.7 U/L for healthy control subjects, P = 0.014; weeks 1-4: 91.8 U/L for anorexia-nervosa patients and 86.2 U/L for bulimia-nervosa patients versus 77.6 U/L for healthy controls, P < 0.001). We assume that the increase in DPP IV serum activity will increase the turnover of distinct peptide hormones with known effects on nutrition control and susceptibility to degradation by DPP IV. The potential impact of an increase in DPP IV activity in serum on satiety and nutrition control contributes to previously reported implications for immune function.

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.

Unlabelled: The involvement of brain serotonin systems in the pathophysiology of eating disorders has been repeatedly demonstrated in recent studies. Platelet MAO activity is an index of brain serotonin activity and lowered platelet MAO levels have been found in association with impulsive behaviors. In addition, some preliminary reports indicate that platelet MAO could be lowered in eating disorder patients., Methods: 47 patients with DSM-IV eating disorders were studied, including 30 with bulimia nervosa and 17 with anorexia nervosa binge eating-purging type. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine and compared with a control group of 30 healthy subjects. Impulsive personality features were studied with specific rating scales., Results: Platelet MAO activity was significantly lower (4.4+/-2.4 nmol/h/10(8) platelets) in the bulimic patients than in the control group (6.9+/-2.5) (p<0.001). No significant differences were found between pure bulimics and binge eating-purging anorectics. Platelet MAO was inversely and significantly correlated with scores on impulsivity scales and with borderline personality disorder characteristics., Conclusions: Platelet MAO activity is lowered in patients with bulimia, which may reflect dysfunction in impulse control mechanisms. Since platelet MAO has a predominant genetic component, there is need for studies on the association of low platelet MAO and higher risk for developing eating disorders.

Objective: To study if platelet MAO activity, previously described as a serotonergic index, is modified in a sample of pure restrictive anorectic patients., Method: Twenty-five female patients with DSM-IV anorexia nervosa restricting type were studied and compared with 30 healthy female controls. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine. Impulsive personality features were measured with specific rating scales and temperament studied with Cloninger's TCI., Results: Platelet MAO activity was significantly lower (4.3+2.7 nmol/h/ 108 platelets) in the anorectic patients than in the control group (6.7+2.8) (P<0.01). Platelet MAO was inversely correlated with scores on impulsivity scales and positively correlated with the dimension 'persistence' of Cloninger's TCI., Conclusion: Platelet MAO activity is lowered in a group of patients with anorexia nervosa and might involve some dysfunction in the regulation of impulse control.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl Peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leukocyte antigen CD26, is considered to participate in T cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 44 patients (anorexia nervosa (AN): n = 21, bulimia (B): n = 23) in four consecutive weekly analyses. The analysis of CD26-positive cells included the characterization of CD26-bright and CD26-dim positive subsets. Additionally, the expression of CD25 (IL-2 Receptor alpha chain) was evaluated to estimate the degree of T cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD26-positive cells were reduced in patients as compared to healthy controls (mean 40.2% (AN) and 41.1% (B) vs. 47.4% (HC), p < 0.01), while the DPP IV activity in serum was elevated (mean 108.4 U/l (AN) and 91.1 U/l (B) vs. 80.3 U/l (HC), p < 0.01). The potential implications of changes in DPP IV expression and serum activity on--and beyond--immune function are discussed.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leucocyte antigen CD26, is considered to participate in T-cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses. In addition, the expression of CD25 (interleukin-2 receptor alpha chain) was evaluated to estimate the degree of T-cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD2-CD26-positive cells were reduced in patients compared with healthy controls [mean 40.2% (AN) and 41.1% (B) versus 47.4% (HC), P < 0.01], while the DPP IV activity in serum was elevated [mean 108.4 U/l (AN) versus 91.1 U/l (B) and 80.3 U/l (HC), P < 0.01]. The potential implications of our observations on, and beyond, immune function are discussed.

To clarify the clinical significance of elevation of serum aminotransferase levels in anorexia nervosa, we analyzed the relationships of serum aminotransferase levels to other serum biochemistry and physical conditions before and during refeeding therapy in 101 patients with anorexia nervosa. Before refeeding therapy, body mass index (BMI) was distributed from 9.9 to 16.4 kg/m2 (13.2 +/- 1.3, mean +/- SD), and 29 patients (28.7%) showed abnormally high aminotransferase levels. Among 17 patients with a BMI of less than 12 kg/m2, the aminotransferase level was abnormally high in 13 patients (76%). Incidence and severity of serum aminotransferase elevation were greater in the patients with lower BMI. The groups with high serum aminotransferase levels had a lower body temperature, lower pulse rate, and higher incidence of other biochemical abnormalities than the group with normal serum aminotransferase levels. These findings indicate that aminotransferase elevation develops at a high incidence in anorectic patients with a critically life-threatening condition, and it is a sign of multiorgan failure requiring urgent calorie repletion. This type of aminotransferase elevation is to be distinguished from refeeding-induced aminotransferase elevation.

A 32 year old woman with a history of anorexia nervosa began experiencing severe muscle weakness. Proximal weakness was worse than distal and she became unable to walk. Serum creatine kinase was elevated 15-fold and EMG was consistent with a myopathic process. Muscle biopsy showed focal areas of absent staining using NADH and ATPase enzyme histochemistry. Gomori trichrome revealed many positive inclusions which were positive using immunohistochemistry for actin. Electron microscopy revealed these areas to contain cytoid bodies with Z-band streaming and disorganization of the myofibrillar network. These findings are consistent with the myopathy associated with ipecac (emetine) toxicity. A urine toxicology screen demonstrated evidence of emetine abuse, which was later admitted by the patient. Following discontinuation of the drug, the patient recovered normal muscle strength.

Nervous anorexia in advanced stage causes a generalized deterioration of organs' and apparatuses' functions. In particular, well-known are disorders of both CNS and PNS, changes of the haematic crasis and worsening of the metabolic-endocrine axis. Less well-known, however, is the compromission of function. Analysis of the data obtained in this trial points out a statistically significant correlation between the loss of weight and the variation of level of some liver enzymes (SGPT, SGOT, LDH). These indexes of hepatic necrosis in our opinion, can therefore, be regarded as sound markers not only for a more careful evaluation of the clinical evolution of the anorexic patient, but also for a better monitoring of the effectiveness of diet therapy.

Accurate data are not available for the prevalence of eating disorders amongst the Asian population in Britain. Only a handful of cases have been reported in the literature [Bhadrinath (1990). British Journal of Psychiatry, 156, 565-568.] suggested that it is an uncommon phenomenon despite Dolan's recent finding [Dolan, Lacey, & Evans (1990). British Journal of Psychiatry, 157, 523-528.] that there were elevated Eating Attitudes Test (EAT) scores in a sample of young Asian adults compared with Caucasians. We report a case of an Asian girl with a rare inborn error of metabolism and an eating disorder.

The authors investigated the significance of vomiting for hyperamylasemia and sialadenosis in patients with bulimia nervosa. Hyperamylasemia was found in 61% of the bulimics and in 20% of the restrictor anorectics but in no patients with binge-eating syndrome. In more than three fourths of the bulimics there was a close positive correlation between the frequency of vomiting and total serum amylase levels. Both frequency and type of vomiting seem to be relevant to the extent of salivary gland enlargement. The significance of vomiting for the etiopathology of hyperamylasemia and for the diagnosis of eating disorders will be discussed.

Thirty-five consecutive attenders at a clinic specializing in anorexia nervosa were studied. All conformed to a DSM-III-R diagnosis for anorexia nervosa. In addition, 3 cases suffered from major depressive disorder and 9 from dysthymia. Blood from all patients was analysed for monoamine oxidase, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), tryptophan and platelet paroxetine binding. Findings showed that blood 5-HT was higher than normal in all patient groups, and was highest in those having affective disorder with anorexia nervosa. However, of the patients with anorexia nervosa alone, a subgroup having greatest weight loss had blood 5-HT levels significantly below all other groups. Lack of significant changes in other parameters compared with normal subjects points to the possibility of abnormal 5-HT storage or release.

In the serum and saliva of 45 patients with eating disorders and in 30 normal controls, alpha-amylase activity and isoamylase levels were measured. Of the 45 patients evaluated, 12 had restrictive anorexia nervosa, 13 were bulimic anorectics and 20 had bulimia nervosa. In all these groups, the mean alpha-amylase values in serum and saliva were higher than that of the control group. The proportion of pancreatic (P)- and salivary (S)-alpha-amylase isoenzymes in serum were within the normal range for the patient group with restrictive anorexia nervosa, whereas the bulimic anorexia nervosa and bulimia nervosa patients showed significantly greater increases in S- than P-isoamylase activity. The correlation of the salivary alpha-Amylase isoenzym pattern in serum and saliva pointed to the salivary glands as origin of the elevated salivary isoamylase levels in serum. Hyperamylasemia was found in 10 (25%) of the 45 patients with eating disorders. Three of these patients showed besides an increased S-alpha-amylase activity also pathologically elevated P-alpha-amylase and lipase activity in serum; however there were no abdominal symptoms, laboratory data or ultrasonic signs of pancreatitis. In all patients with eating disorders, the mean concentration and secretion of alpha-amylase in saliva were increased. Swelling of the salivary glands was present in 14 patients. In these cases the percentage of salivary-isoamylase activity in total serum alpha-amylase activity was increased significantly, whereas the alpha-amylase secretion in the resting saliva was decreased.

Biopsies from four young women with advanced anorexia nervosa were examined to investigate the effect of malnutrition on skeletal muscles. None of the patients showed signs of neuromuscular disease and all were physically active at the time of examination. Cryostat sections from the vastus lateralis muscle were stained with hematoxylin-azophloxin-safran and with stains for myofibrillar ATP-ase activity. In addition to routine examination of the sections, the size and distribution of the type 1 and type 2 fibres were calculated by means of a Kontron Digiplan MOP 02. Routine stained sections showed a small grouped atrophy in three cases and a more diffuse atrophy in the fourth. Enzyme histochemical stains revealed a distinct type 2 atrophy, a finding which should serve to distinguish the changes of pure malnutrition from those of conventional denervation. Exact measurements confirmed the predominant type 2 atrophy but showed definite atrophy also of the type 1 fibres. Compared with normal controls the type 1 fibres were reduced by 46% and the type 2 fibres by 75%. These findings are largely in agreement with the recent observations by Essén et al. (1981) on anorexia nervosa. However, in contrast to Essén et al. we did not find any change in the numerical distribution of the fibre types, especially no increase in type 1 fibres. Thus, we could not confirm the hypotheses of a conversion of the fibre types in cachexia.

Hyperamylasemia and parotid hypertrophy are conditions found in bulimic patients. The authors studied serum amylase levels in 56 underweight anorectics, 24 weight-recovered anorectics, 23 normal-weight bulimics, and 31 volunteer women. Normal-weight bulimic patients had significantly higher admission serum amylase values (mean +/- SE = 73.4 +/- 8.0 IU/L) than controls (40.8 +/- 2.4 IU/L). Additionally, the serum amylase test distinguished between restrictor anorectics (N = 31, 44.7 +/- 4.7 IU/L) and bulimic anorectics (N = 25, 68.8 +/- 8.6 IU/L, p less than .05) with a high degree of specificity and a fair degree of sensitivity. A subsample (N = 7) of bulimics showed twofold to fourfold increases in serum amylase values after a controlled period of binge eating and vomiting, whereas normal volunteers showed no change in serum amylase values (p less than .001) after ingesting a large meal. Serum amylase values declined significantly within 6 to 15 days of admission. However, after passes off the unit, serum amylase values returned to admission values, presumably as a result of binge-vomit episodes. The authors observe that modest increases of serum amylase values appear to be a consequence of binge-vomit behavior and suggest that serial serum amylase determination may be useful in monitoring the degree of patient abstinence in therapeutic programs.

Studies are reviewed that address the question of whether anorexia nervosa is associated with abnormalities in central nervous system catecholamine metabolism. There is some support for the hypothesis that norepinephrine and dopamine metabolism are altered in this disorder.

Adaptation of coenzyme stimulation assays for the nutritional assessment of thiamine, riboflavin and pyridoxine on the Cobas Bio centrifugal analyser are described. Whole blood was collected into acid-citrate dextrose, which preserves the erythrocytes, prior to assay for several days. Washed erythrocytes stored at -70 degrees C and subsequently thawed, showed altered enzyme activities. The methods offer improved precision over existing procedures and take advantage of the high throughput capabilities of the instrumentation.

The intake laboratory data of 46 patients seen between 1970 and 1980 who were less than 19 years of age with a discharge diagnosis of anorexia nervosa were retrospectively reviewed to determine their metabolic profile. The major findings for those who had laboratory data were as follows: 45% (19/42) had serum glutamic oxalacetic transaminase (SGOT) values greater than 36 International Units/liter (IU/L), and 65% (27/41) had alkaline phosphatase levels less than 58 IU/L. We suggest that patients with anorexia nervosa may reflect a state of hepatic dysfunction and/or dehydration before therapy.

The levels of components of the fibrinolytic enzyme system in 7 patients with anorexia nervosa were compared with those of healthy young women. Plasminogen activator levels were significantly higher and the mean fibrinogen concentration was lower in the anorexia nervosa patients.

Salivary isoamylase levels were studied in a sample of 35 women with bulimia, anorexia nervosa, or bulimia nervosa. Salivary isoamylase elevation was related to the presence of sham eating, evidenced by elevated isoamylase values in patients with bulimia nervosa or bulimia, and depressed isoamylase values in patients with anorexia nervosa. Salivary isoamylase levels may provide insight and have bearing on the functional interrelationship between appetite regulation and ingestive behavior in patients with eating disorders, as abnormalities may occur during both the cephalic as well as the oral phase of eating.

Angiotensin-converting enzyme (ACE) activity was measured in 10 patients with anorexia nervosa, 6 with hyperthyroid Graves' disease, and 7 with primary hypothyroidism. Patients with anorexia nervosa had a low serum ACE activity (9.8 +/- 2.2 IU/l), as compared to findings in normal subjects (13.4 +/- 3.5 IU/l) (P less than 0.05). Patients with hyperthyroid Graves' disease had high serum ACE activity (23.7 +/- 5.8 IU/l), as compared to levels in normal subjects (P less than 0.01), and patients with primary hypothyroidism tended to have low serum ACE activity (10.1 +/- 1.8 IU/l), compared to the normal subjects (P less than 0.1). Following weight gain (before; 71.3 +/- 10.2% of ideal body weight, after; 88.7 +/- 5.6% of ideal body weight), serum ACE activity in patients with anorexia nervosa reverted to within the normal range (13.8 +/- 3.5 IU/l), and serum T3 concentration was restored to the normal range (before; 0.7 +/- 0.2 ng/ml, after; 1.1 +/- 0.3 ng/ml). In these patients, ACE activity correlated with the per cent of ideal body weight (P less than 0.05). These data suggest that, in underweight subjects with anorexia nervosa, decreased serum ACE activities may relate to emaciation.

10 patients with anorexia nervosa were compared with controls with normal weight, regarding their peripheral blood polymorphonuclear (PMN) granulocyte reactions. The anorexia patients showed a statistically significant decrease in PMN bactericidal capacity and PMN adherence. The mean chemotaxis did not differ, but in two of the anorexia patients chemotaxis was almost absent. The intracellular activity of alkaline phosphatase was below the reference values in 5 of the 6 patients in whom it was investigated. It is concluded that changes in granulocyte function may be noted in anorexia nervosa, but their clinical significance is uncertain, as no patients had recurrent or severe infectious diseases.

In patients with eating disorders, we evaluated pancreatic abnormalities using serum elastase 1 measurement by RIA and the 50 g oral glucose tolerance test (50 g OGTT). Twenty-one patients had anorexia nervosa (AN) with bulimia and vomiting (AN-B group), 30 had AN without bulimia or vomiting (AN-R group), and 25 had bulimia with normal body weight (B group). The serum elastase 1 level was determined on admission and repeated after body weight gain in 43 anorectic patients. The 50 g OGTT was performed within 2 weeks after admission. The serum elastase 1 level in the AN-B group (363 +/- 47 ng/dl, M +/- SE), and in the AN-R group (352 +/- 37) were significantly higher than that in the B group (242 +/- 18) or in the healthy female controls (191 +/- 10; n = 13). A significant decrease of serum elastase 1 was observed before and after body weight gain; however, there was no significant correlation between the serum elastase 1 level and insulin response to the 50 g OGTT. Elevation of the serum elastase 1 level in AN suggests pancreatic abnormalities other than those related to endocrinological events.

Platelets alpha 2-adrenoceptors were studied in 24 patients with anorexia nervosa shortly after admission to the hospital and after 10% weight gain. Twenty patients with bulimia and 24 healthy age- and sex-matched normal subjects also were studied. Receptor number was significantly increased in patients with bulimia and anorexia nervosa. After 10% weight gain, the receptor number almost normalized in anorexia nervosa patients. Kd values were increased in all patients groups at all times of study. In patients with bulimia or anorexia nervosa, both initially and after weight gain, the maximal effect of prostaglandin E1 (PGE1) on platelet cAMP production was greatly increased, while the half-maximally effective dose was unchanged. Also, the maximal inhibitory effects of epinephrine and clonidine on PGE1-stimulated platelet cAMP production were greater, while the half-maximal dose of both alpha 2-agonists was unchanged. Metabolic and endocrine indicators of starvation were present in both bulimic and anorexia nervosa patients initially. Blood beta-hydroxybutyric acid was elevated, and plasma T3 values and the orthostatic response of plasma norepinephrine (delta NA) were reduced, while cortisol was elevated (only in anorexia nervosa patients). Among these parameters, only delta NA significantly correlated with the actions of PGE1 and epinephrine on cAMP production. In conclusion, the activity of the sympathetic nervous system was reduced in patients with anorexia nervosa and bulimia. This reduction was accompanied by an increased capacity and a decreased affinity of platelet alpha 2-receptors and an increased PGE1 stimulatory and epinephrine inhibitory effects on cAMP production.

Platelet MAO activity was determined in 33 anorexia nervosa patients. A subgroup of 15 patients who met Research Diagnostic Criteria for a concomitant major depressive disorder were found to have, both initially and after 5 weeks of treatment, significantly lower mean platelet monoamine oxidase (MAO) activity than 28 matched normal control subjects. In contrast, mean platelet MAO activity in the patients who did not meet criteria for major depressive disorder was similar to values in control subjects. The authors found that significantly more depressed patients had low MAO activity compared with nondepressed patients and controls. Platelet MAO activity may be useful in discriminating among subtypes of anorexia nervosa patients.

Hyperamylasemia, which has been reported in patients with the eating disorders anorexia nervosa and bulimia, generally has been thought to result from pancreatitis. To evaluate the mechanisms of hyperamylasemia, we measured amylase, lipase, and isoamylase activity in 17 consecutive patients admitted to the eating disorder unit. Six patients had elevated amylase activity, and 5 of these 6 had isolated increases in salivary isoamylase activity. Six other patients had normal serum total amylase activity but modest elevations in the salivary isoamylase fraction. No patient developed clinical evidence of pancreatitis during hospitalization. Thus, the hyperamylasemia in patients with anorexia and bulimia often is caused by increased salivary-type amylase activity. The appropriate diagnostic test for hyperamylasemia in patients with anorexia or bulimia is the simple measurement of serum lipase or pancreatic isoamylase activity. If these levels are found to be normal, further tests to exclude pancreatitis are unnecessary.