Immunological findings in anorexia and bulimia nervosa

Cytofluorometric studies, using monoclonal antibodies directed against surface antigens of mononuclear blood cells, were conducted in 10 patients with anorexia nervosa, 12 patients with bulimia nervosa, and in 9 healthy, age matched controls. While total leukocytes were not different between groups, the number of lymphocytes was significantly reduced in anorectic but not in bulimic patients. The number of T- but not of B-lymphocytes and monocytes/macrophages was diminished. All T-cell populations (helper/inducer = CD4); suppressor/cytotoxic = CD8) and CD57 positive natural killer (NK) cells were reduced in anorexia nervosa. This effect is probably caused by increased glucocorticoid secretion.     

Alterations in serum cortisol, CD4+ CD8+ lymphocyte sub-population ration and T cell mediated suppression of immune responses in the malnutrition of anorexia nervosa

Serum cortisol and T lymphocyte sub-populations (CD3+, 4+ and 8+) were studied in 22 consecutively admitted patients with anorexia nervosa (AN) who had a mean weight loss of 30%. In addition Concanavalin A (Con A) mitogen induced T cell suppression of lymphocyte response to PPD (purified protein derivative of tuberculin antigen) was analysed. Increased serum cortisol concentrations were found in the AN-patients compared to the control group, with mean levels 654 and 418 nmol/l respectively. The relative numbers of CD4+ lymphocytes (mean 36.2%) and the CD4+ CD8+ ratio (mean 1.54) were significantly reduced (p < 0.05) in the AN-patients compared to the control group (mean 41.6% and 2.14 respectively). T cell mediated, Con A induced suppression of lymphocyte response to PPD was increased in AN-patients compared to the control group with low (1mug/ml) Con A concentration, but unchanged with high (5 mug/ml) Con A concentration. There was no correlation between serum cortisol concentrations and the numbers of T lymphocyte subpopulations or T cell suppressor activity. In contrast, a highly significant correlation existed between serum cortisol and the duration of AN (p < 0.002), but not with relative weight loss or anthropometric variables: triceps skin-fold (TSF) and arm muscle circumference (AMC). Immunological variables were not correlated with duration of disease. Thus, immunological alterations of the T cell system are detectable in AN, but are subtle and their clinical importance is not well known.     

Establishing guidelines for pharmacotherapy trials in bulimia nervosa and anorexia nervosa

OBJECTIVE: This paper addresses the lack of a standard protocol for pharmacotherapy trials for patients with bulimia nervosa (BN) and anorexia nervosa (AN). METHOD: Twenty-two surveys were sent to established researchers in the field of eating disorders to elicit their opinions regarding medication trials, including baseline laboratory tests, the optimal length/frequency of medication management sessions, and the information that should or should not be included in these sessions. RESULTS: Sixteen of 22 researchers completed and returned the survey. Their answers are the basis of the data presented. DISCUSSION: We propose a battery of screening laboratory tests for both conditions. We suggest 30-45-min initial medication management sessions in both AN and BN trials with 15-min follow-ups to be held weekly for AN subjects, and weekly for 2 weeks, then biweekly for 2 weeks, then monthly, for BN subjects. We also recommend that published trials should include explicit details of medication management.     

Effects of a nutritional intervention with yogurt on lymphocyte subsets and cytokine production capacity in anorexia nervosa patients

Summary Background The benefits of probiotic therapy in immunocompromised subjects still need strong scientific evidences. Aim of the study To assess the effects of yogurt on certain immunological parameters in anorexia nervosa (AN) patients during refeeding. Methods A parallel 10-week nutritional intervention with yogurt was conducted on a group of patients with AN and on a group of healthy adolescents (HA). In total, 16 AN patients and 16 HA consumed 375 g/d of yogurt containing L. bulgaricus and S. thermophilus (groups AN-y and HA-y, respectively). The control groups for AN patients (n = 14) and healthy subjects (n = 19) consumed 400 ml/d of semi-skimmed milk (groups AN-c and HA-c, respectively). Blood lymphocyte subsets were assessed by flow cytometry and the in vitro production of IL-2, IFN-γ, IL-1, IL-6 and TNF-α by PHA-stimulated PBMC was measured by ELISA. Results A significant combined effect of time and nutritional intervention was found for the CD8+ subset and IFN-γ production, both in HA and AN patients. The CD8+ subset showed a significant increase after 10 weeks in HA-c and AN-c. As a consequence, the CD4+/CD8+ ratio was significantly lower in AN-c than in AN-y after treatment. A significant increase in IFN-γ production was found after yogurt intake in AN-y, while it decreased significantly in AN-c. Conclusion The findings suggest that the inclusion of yogurt in the refeeding therapy of AN patients may exert positive effects on the immunological markers related to the nutritional status of these patients, such as the CD4+/CD8+ ratio and the production of IFN-γ by lymphocytes.     

The adaptive response of the immune system to the particular malnutrition of eating disorders

Despite the seriously undernourished state of patients with anorexia nervosa (AN) and bulimia nervosa (BN), controversial findings have been published regarding some aspects of the immune system that are otherwise impaired in more typical types of malnutrition, such as protein-energy malnutrition. In general, adaptation processes seem to occur enabling immune function to be preserved during long periods of the illness. However, cell-mediated immunity is usually altered in AN and BN as reflected by lymphocyte subset counts and the response to delayed hypersensitivity tests. Regarding the helper/cytotoxic T cell ratio (CD4:CD8), an immunological marker of the nutritional status, the results of our studies on AN and BN patients showed that the duration of the eating disorder and the time when appropriate treatment is achieved are likely contributors to the alteration of this ratio. Despite these findings, it has been repeatedly pointed out that anorexic patients seem to be free of common viral infections at least until the most advanced stages of debilitation. Some hypotheses that could explain the lack of infection symptoms are reviewed. Cytokines and the altered acute phase response to infection, as well as cortisol and leptin, are considered to be potential factors involved in the adaptation processes occurring in these syndromes. Further progress in the knowledge of the psychoneuroendocrine-immune interactions established in AN and BN will be relevant to the understanding of the aetiology and maintenance mechanisms of these pathologies.     

Neuropsychological study of underweight and "weight-recovered" anorexia nervosa compared with bulimia nervosa and normal controls

OBJECTIVE: To compare executive, memory and visuospatial functioning of DSM-IV anorexia nervosa (AN), bulimia nervosa (BN), and normal controls (NC). METHOD: A comparison of women involving: (i) 16 AN with body mass indices (BMI) < or = 17.5 kg/m(2); (ii) 12 AN with BMI > 18.5 kg/m(2) for at least 3 months; (iii) 13 BN; and (iv) 16 NC participants was performed with groups of similar age and intelligence. Groups were assessed with EDE-12, MADRS, HAMA, Cognitive Drug Research (CDR) battery, and Bechara tasks. RESULTS: Significant impairments in CDR Power of Attention were present in underweight AN and BN participants. CDR Morse Tapping was significantly impaired in all clinical groups. The BN and weight-recovered AN groups were significantly impaired on CDR immediate word recall. The BN group alone was significantly impaired on CDR delayed word recall. CONCLUSION: Attentional impairment is similar in AN and BN. Impaired motor tasks in AN persist after "weight-recovery" and are similar to impairments in BN. BN may be discriminated from AN on word recall.     

Investigation of regulatory T cells in anorexia nervosa

OBJECTIVE: The aim of our study was to determine, how severe calorie restriction in anorexia nervosa (AN) may influence regulatory T (Treg) cells and their cellular networks, that is, their main inducers (dendritic cells (DC) and monocytes) and their target cells, CD4+ lymphocytes. DESIGN: We measured the prevalence of Tregs, myeloid and plasmocytoid DC. The prevalence of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12-positive monocytes, IL-2, IL-4 and interferon (IFN)-gamma positive CD4+ cells was determined by intracellular staining after activation. SETTING AND SUBJECTS: In total, 21 AN patients and 19 healthy age-matched controls (body mass index values, median (range): 14.9 (11.1-17.4) vs 23.2 (19.5-27.4) kg/m(2)) have been recruited. RESULTS: Prevalence of Tregs, DCs, TNF-alpha and IL-12-positive monocytes, IL-4 and IFN-gamma-producing CD4+ cells were similar in AN and controls. The prevalence of IL-2-positive CD4+ cells was somewhat lower in AN (% value, median (range): 12.05 (7.50-16.70) vs 14.40 (12.00-22.00), P<0.05). None of these parameters correlated with the patients' clinical characteristics. CONCLUSIONS: Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis is not affected by calorie and nutritional deficiency.     

Subjective binge eating with compensatory behaviors: A variant presentation of bulimia nervosa

Objectives:

To determine whether a variant bulimic‐type presentation, whereby one meets criteria for bulimia nervosa (BN) except that binge eating episodes are not objectively large (i.e., “subjective bulimia nervosa,” SBN), has comparable clinical severity to established eating disorders, particularly BN.

Method:

Treatment‐seeking adults with BN (N = 112), SBN (N = 28), anorexia nervosa restricting type (AN‐R) (N = 45), and AN‐binge/purge type (AN‐B/P) (N = 24) were compared.

Results:

Overall, SBN could not be meaningfully distinguished from BN. SBN and BN had equivalent eating pathology, depression and anxiety symptoms, low quality of life, impulsivity, Axis I comorbidity, and lifetime psychiatric history, and comparable clinical severity to AN‐R and AN‐B/P.

Discussion:

Individuals with SBN, differing from BN only by the smaller size of their binge eating episodes, had a form of eating disorder comparable in clinical severity to threshold AN and BN and warranting clinical attention. Health professionals and the community require greater awareness of this variant to optimize detection, treatment‐seeking, and outcomes. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)     

Prevalence of anorexia nervosa and bulimia nervosa in a geographically defined area in Japan

OBJECTIVE: Little has been understood regarding the frequency of eating disorders in Japan. This study was designed to identify the prevalence of anorexia nervosa (AN) and bulimia nervosa (BN) in Japan. METHOD: We asked doctors in all of the relevant medical facilities (130 hospitals and 1,326 clinics) in Niigata Prefecture to report patients with DSM-IV-diagnosed eating disorders who appeared or were admitted between 20-24 October 1997. The response rate was 94.4%. RESULTS: The estimated point prevalences of AN and BN were 4.79 and 1.02, respectively, per 100,000 females. Specifically for the age group of 15-29 years, the prevalence of AN was 17.10 and that of BN 5.79. DISCUSSION: The prevalence of AN and BN in Japan is lower than that for European Caucasian populations. This result may be due to cultural and ethnic differences and/or it may be a transient phenomenon.     

Eating Disorders Examination versus Eating Disorders Examination-Questionnaire in adolescents with full and partial-syndrome bulimia nervosa and anorexia nervosa

OBJECTIVE: The current study compared the Eating Disorders Examination (EDE) and the Eating Disorders Examination-Questionnaire (EDE-Q) in adolescents with eating disorders. METHOD: Adolescents (N = 70) with bulimia nervosa (BN; n = 21), partial-syndrome BN (PBN; n = 25), and anorexia nervosa (AN; n = 24) were assessed with the EDE and EDE-Q. RESULTS: Moderate to high correlations were found on all four subscales within and between diagnostic groups. The discrepancy between the EDE and EDE-Q was significantly greater in BN relative to PBN and AN for the Eating Concern subscale. Objective binge episode (OBE) frequency in BN and subjective binge episode (SBE) frequency in BN and PBN were higher with the EDE compared with the EDE-Q. Self-induced vomiting was highly correlated between the two measures. DISCUSSION: Adolescents with BN, PBN, and AN exhibited strong correspondence between the EDE interview and questionnaire formats. However, this consistency was not as pronounced for BN as it was for PBN and AN. The current study lends preliminary credibility to the use of the EDE-Q in adolescent eating disorder samples.     

Malnutrition induces dissociated changes in lymphocyte count and subset proportion in patients with anorexia nervosa

OBJECTIVE: The effect of nutritional state on lymphocytes in patients with anorexia nervosa (AN) was studied. METHOD: We studied total lymphocyte count (TLC), lymphocyte subsets, and nutritional markers [body mass index (BMI), insulin-like growth factor-1 (IGF-I)], and serum zinc concentration) in 33 patients with AN and 10 healthy controls. RESULTS: TLC positively correlated with BMI (r = .680, p < .001), IGF-I (r = .609 p < .001), and zinc (r = .589, p < .001). The CD4+ T-lymphocyte (CD4) proportion correlated negatively with BMI (r = -.301, p = .05) and IGF-I (r = -.346, p = .023), counteracting the effect of malnutrition on TLC. However, because this increase in CD4 proportion was weak, patients with very severe malnutrition (indicated by serum zinc less than 40 microg/dL) had critically low CD4 counts of less than 200 cells/microL. CONCLUSION: Our findings suggest that lymphocyte counts and subset proportion change in an opposite manner in patients with AN, and that decrease in serum zinc levels is nutrition-related.     

Fractures in patients with anorexia nervosa,bulimia nervosa,and other eating disorders--a nationwide register study

OBJECTIVE: To study fracture risk in patients with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorders not otherwise specified (EDNOS). METHOD: Cohort study including all Danes diagnosed with AN (n = 2,149), BN (n = 1,294), or EDNOS (n = 942) between 1977 and 1998. Each patient was compared with three randomly drawn age- and gender-matched control subjects. RESULTS: Fracture risk was increased in AN after diagnosis compared to controls (incidence rate ratio: 1.98, 95% CI: 1.60-2.44), but not before. The increased fracture risk persisted more than 10 years after diagnosis. A significant increase in fracture risk was found before diagnosis in BN (1.31, 95% CI: 1.04-1.64), with a trend towards an increase after diagnosis (1.44, 95% CI: 0.93-2.22). EDNOS patients had a significant increase in fracture risk before (1.39, 95% CI: 1.06-1.81) and after diagnosis (1.77, 95% CI: 1.25-2.51). DISCUSSION: The increased fracture risk many years after diagnosis indicates permanent skeletal damage.     

Full syndromal versus subthreshold anorexia nervosa,bulimia nervosa,and binge eating disorder: a multicenter study

OBJECTIVE: The diagnostic criteria for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) establish symptom severity levels, which are used to separate full cases from partial cases. However, the value of these distinctions is unclear. METHOD: Three hundred eighty-five women with full or partial AN, BN, or BED were assessed at entry into a longitudinal study of eating disorders. RESULTS: Stepwise discriminant analysis revealed that full and partial BN were discriminated by the Yale-Brown-Cornell Eating Disorders Scale total scores (kappa =.46). However, it was not possible to discriminate between full and partial AN or BED. Discriminant analysis also demonstrated clear differences between full AN, BN, and BED. DISCUSSION: Full BN can be differentiated from partial BN by more severe eating disorder symptoms, whereas both full and partial AN and full and partial BED appear quite similar. These results emphasize the distinct nature of AN, BN, and BED, as well as the similarities between full and partial cases.     

Specific and nonspecific comorbidity in anorexia nervosa

OBJECTIVE: This article reports lifetime Axis I and II comorbidity in women with anorexia nervosa (AN), and ascertains specific and nonspecific comorbidity in AN compared to clinical samples of women with bulimia nervosa (BN) or major depression (DEP). METHOD: Outpatient AN (n = 56), BN (n = 132), and DEP (n = 100) samples were assessed using Structured Clinical Interviews I and II for DSM-III-R. Baseline data were compared using univariate statistics and logistic regression. RESULTS: In the AN sample as a whole, specific elevations were found for prevalences of obsessive compulsive disorder. The AN-binge eating purging subtype (AN-BP) and the BN sample had elevated prevalences of Cluster B personality disorders. Cluster C prevalences were elevated across samples. CONCLUSION: Evidence of AN-specific, eating disorder-specific, and nonspecific comorbidity illustrates the heterogeneity in AN. Further research is need to examine the relative impact of specific and nonspecific comorbidity in AN subtypes and AN as a whole.     

A comparison of early family life events amongst monozygotic twin women with lifetime anorexia nervosa, bulimia nervosa, or major depression

OBJECTIVES: To investigate the differential profile of early family life events associated with lifetime anorexia nervosa (AN), bulimia nervosa (BN), and major depression (MD). METHOD: Only data from the monozygotic twins (n = 622) were examined from a community sample of female twins who had participated in three waves of data collection. Eating disorder and MD diagnoses were ascertained from the Eating Disorder Examination at Wave 3 and interview at Wave 2 respectively. Early family events were ascertained from self-report measures at Waves 1 and 3. Two case control designs were used, including a comparison of women: (1) who had lifetime AN, BN, MD, and controls, and (2) twin pairs discordant for either AN, BN, or MD (where the unaffected cotwin formed the control group). RESULTS: Across the two types of designs, compared to controls, both AN and BN were associated with more comments from the family about weight and shape when growing up. AN was uniquely associated with higher levels of paternal protection while BN was associated with higher levels of parental expectations. CONCLUSION: While some overlap among early life events was indicated, especially related to parental conflict and criticism, there was evidence to support some degree of nonoverlap among life events associated with AN, BN, and MD.     

Regional cerebral blood flow after recovery from anorexia or bulimia nervosa

OBJECTIVE: Abnormalities of regional cerebral blood flow (rCBF) have been found in individuals who are ill with anorexia (AN) or bulimia nervosa (BN). Little is known about whether rCBF normalizes after recovery from AN and BN. METHOD: Eighteen control women (CW), 10 recovered restricting type AN, 8 recovered AN with a binging history, and 9 recovered BN participants without a history of AN were studied using positron emission tomography and [(15)O]water in order to assess rCBF. RESULTS: Partial volume corrected rCBF values in cortical and subcortical brain regions were similar between groups. Neither current body mass index nor age correlated with rCBF values. CONCLUSION: The results from this study indicate that rCBF normalizes with long-term recovery. Thus, altered rCBF is unlikely to confound functional imaging studies in AN or BN after recovery.     

Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity

OBJECTIVE: We previously reported elevated serum levels of the cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients with anorexia nervosa (AN). We investigated the cellular production of these two cytokines and of interferon-gamma (IFN-gamma), interleukin-1alpha (IL-1alpha), and tumor necrosis factor-alpha (TNF-alpha) in subjects with AN, bulimia nervosa (BN), and obesity as well as in normal-weight control subjects. METHODS: Supernatant fluids from isolated peripheral blood mononuclear cells (PBMC) incubated with and without concanavalin A (ConA) were assayed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences across the four groups were found in the stimulated cellular production of IFN-gamma and IL-6. Stimulated IFN-gamma production was elevated in the AN group compared to controls. IL-6 production was significantly elevated in obese subjects relative to the two normal-weight groups, BN and controls, and tended to be higher in the AN group than in the controls, but not significantly so. IL-1alpha production was greater in obese subjects. CONCLUSION: The findings of increased IFN-gamma production and a tendency toward increased IL-6 production (both of which suppress food intake in animals) in individuals who severely restrict food intake suggest a potential role for these cytokines in the pathogenesis of AN. Elevated IL-6 and IL-1alpha production by PBMC in obese individuals requires further investigation to determine if these cytokines contribute to the development or perpetuation of obesity.     

College students' mental models for recognizing anorexia and bulimia nervosa

Knowledge about eating disorders influences lay people's ability to recognize individuals with anorexia nervosa (AN) and bulimia nervosa (BN) and refer them to professional treatment. We assessed mental models (stored knowledge) of AN and BN in 106 college students. Results indicated that most students have general, but not specific, information about AN and BN's symptoms, consequences, causes, duration, and cures. They also believe that people with eating disorders tend to be young, White women. These findings suggest that lay recognition of eating disorders may be based primarily on observations of dysfunctional eating behaviors and therefore facilitated by additional knowledge.     

Distribution of naïve (CD45RA+) and memory (CD45RO+) T-cells in HIV-infected Puerto Rican population

HIV infection usually results in a gradual deterioration of the immune system. It is evident that early recognition of progression markers during HIV infection from asymptomatic to symptomatic state is needed. In the present cross-sectional study, peripheral blood lymphocytes from 63 HIV-infected Puerto Rican individuals were analyzed by two-color flow cytometry to study the co-expression CD45RA and CD45RO on both CD4+ and CD8+ T-cells and its correlation with age, gender, CD4 count, CD4:CD8 ratio, anti-retroviral therapy, clinical status, and viral load. Measurement of T-cell subsets in these patients showed an excessive increase of CD3+CD8+, CD8+CD45RA+, and CD8+CD45RO+ T-cells as disease progresses. In contrast, it was also observed a significant decrease in CD3+CD4+, CD4+CD45RA+ and CD4+CD45RO+ T-cells. The distribution of CD8+CD45RA+ T-cells did not change significantly between HIV and AIDS cases suggesting that this T-cell subset is not a good progression marker. Interestingly, CD4+CD45RA+ T-cells were significantly difference between genders, and CD44+CD45RA+ and CD8+CD45RO+ T-cells were influenced by age. In conclusion, the distribution of na?ve/memory CD4+ T-cells and memory CD8+ T-cells significantly correlate with HIV infection in disease progression. It is also important to mention that these T-cell subpopulations may be influenced by both gender and age. Overall, these results suggest that a loss in the generation of new immune response and function may be occurring during disease progression. This study open new windows of understanding that will be beneficial for future studies on immunopathogenesis, diagnosis, prognosis, and treatment monitoring for HIV/AIDS.