Long-Term Dynamics of Serum α-MSH and α-MSH-Binding Immunoglobulins with a Link to Gut Microbiota Composition in Patients with Anorexia Nervosa.

INTRODUCTION: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition. METHODS: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females. RESULTS: We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG but not of α-MSH peptide in patients with AN were low at hospital admission but recovered 1 year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score correlated positively with α-MSH IgG in both groups studied but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls. CONCLUSION: We conclude that IgG in the blood plays a role as an α-MSH-binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition.

Serum levels of adiponectin differentiate generalized lipodystrophies from anorexia nervosa.

PURPOSE: The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy. METHODS: Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects. RESULTS: Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN. CONCLUSION: Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN.

A prospective observational study comparing rates of medical instability between adolescents with typical and atypical anorexia nervosa.

BACKGROUND: Recognition of atypical anorexia nervosa (AAN) has challenged underweight as a defining factor of illness severity in anorexia nervosa (AN). The present study aimed to compare rates of medical instability in adolescents with underweight (AN) and non-underweight (AAN) anorexia nervosa. METHODS: The study examined assessment data from specialist eating disorder services in the UK between January and December 2022. Participants (n = 205) aged 11-18 years were recruited across eight eating disorder clinics and diagnosed with AN (n = 113) or AAN (n = 92) after clinical assessment. Parameters associated with risk of medical instability were compared between AN and AAN groups, using t tests and regression analysis. RESULTS: Rates of bradycardia and hypotension did not differ significantly between AN and AAN groups (p = 0.239 and p = 0.289). Although white blood cell counts were lower in the AN group, rates of leukopaenia could not be statistically compared as a result of there being too few counts in at least one group. No incidences of hypophosphataemia were found in the sample. A significant regression equation was found for percentage median body mass index, but not rate of weight loss, as a predictor of blood pressure, serum phosphorous and magnesium. CONCLUSIONS: Our findings indicate that medical instability occurs across a range of body weights in young people with AN and AAN. Although certain parameters of risk such as blood pressure, serum phosphorous and magnesium may be worsened at lower weight, both AN and AAN are serious mental health conditions that can lead to medical instability.

SIRT1 Serum Concentrations in Lipodystrophic Syndromes.

Lipodystrophies (LDs) are rare, complex disorders of the adipose tissue characterized by selective fat loss, altered adipokine profile and metabolic impairment. Sirtuins (SIRTs) are class III NAD+-dependent histone deacetylases linked to fat metabolism. SIRT1 plays a critical role in metabolic health by deacetylating target proteins in tissue types including liver, muscle, and adipose. Circulating SIRT1 levels have been found to be reduced in obesity and increased in anorexia nervosa and patients experiencing weight loss. We evaluated circulating SIRT1 levels in relation to fat levels in 32 lipodystrophic patients affected by congenital or acquired LDs compared to non-LD subjects (24 with anorexia nervosa, 22 normal weight, and 24 with obesity). SIRT1 serum levels were higher in LDs than normal weight subjects (mean ± SEM 4.18 ± 0.48 vs. 2.59 ± 0.20 ng/mL) and subjects with obesity (1.7 ± 0.39 ng/mL), whereas they were close to those measured in anorexia nervosa (3.44 ± 0.46 ng/mL). Our findings show that within the LD group, there was no relationship between SIRT1 levels and the amount of body fat. The mechanisms responsible for secretion and regulation of SIRT1 in LD deserve further investigation.

Serum peripheral markers for inflammation in adolescents with anorexia nervosa.

BACKGROUND: There is a limited number of studies comparing the levels of inflammation in adolescent patients with anorexia nervosa (AN) and healthy controls based on complete blood count and platelet parameters. METHODS: This study is a retrospective cross-sectional analysis of 53 drug-naive patients with AN and 53 healthy controls. RESULTS: Significant differences were observed for WBC (white blood cell), neutrophil, MCV (mean corpuscular volume), MCH (mean corpuscular haemoglobin) and neutrophils/lymphocytes ratio (NLR) between the study groups. Patients with AN had lower WBC, neutrophiles and NLR values. But there was no difference between the groups in terms of inflammation-related platelet parameters. A strong positive correlation between BMI (body mass index) and PLT (platelet), PCT (plateletcrit) was determined in the patient group (r = 0.454, p = 0.001; r = 0.386, p = 0.007). Inflammation-related parameters may increase as BMI increases with nutrition and weight restoration. CONCLUSIONS: The present study provides further evidence for level of inflammation in these patients does not increase during the acute period, unlike other mental diseases.

The influence of homeostatic mechanisms on neural regulation of food craving in anorexia nervosa.

BACKGROUND: Restrictive food intake in anorexia nervosa (AN) has been related to an overactive cognitive control network inhibiting intuitive motivational responses to food stimuli. However, the influence of short-term homeostatic signaling on the neural regulation of cue-induced food craving in AN is still unclear. METHODS: Twenty-five women with AN and 25 matched normal-weight women were examined on two occasions after receiving either glucose or water directly into their stomach using a nasogastric tube. Participants were blinded to the type of infusion. An event-related functional magnetic resonance imaging paradigm was used to investigate the effect of intestinal glucose load on neural processing during either simple viewing or distraction from food stimuli. RESULTS: Neural differences between patients with AN and normal-weight participants were found during the distraction from food stimuli, but not during the viewing condition. When compared to controls, patients with AN displayed increased activation during food distraction in the left parietal lobule/precuneus and fusiform gyrus after water infusion and decreased activation in ventromedial prefrontal and cingulate regions after intestinal glucose load. CONCLUSIONS: Independent of the cephalic phase and the awareness of caloric intake, homeostatic influences trigger disorder-specific reactions in AN. Food distraction in patients with AN is associated with either excessive higher-order cognitive control during physiological hunger or decreased internally directed attention after intestinal glucose load. These findings suggest that food distraction plays an important role in the psychopathology of AN. This study was registered on clinicaltrials.gov with identifier: NCT03075371.

Does physical activity associated with chronic food restriction alleviate anxiety like behaviour, in female mice?

Anorexia nervosa (AN) is an eating disorder characterized by excessive weight loss, persistent food restriction and inappropriate physical activity relative to declining energy balance. The comorbidity with depression and/or anxiety disorders might contribute to the "chronicization" of the disease. We aimed here to question first the link between physical activity and anxiety from a clinical investigation of AN patients (n = 206). Then, using a rodent model mimicking numerous physiological and metabolic alterations commonly seen in AN patients, we examined whether 1) chronic food restriction increased anxiety-like behaviour and 2) physical activity plays a role in regulating anxiety levels. To this end, we exposed young female mice to a chronic food restriction (FR, n = 8) paradigm combined or not with access to a running wheel (FRW, n = 8) for two weeks. The mice were compared to a group of mice fed ad libitum without (AL, n = 6) or with running wheel access (ALW, n = 8). We explored anxiety-like behaviour of all mice in the following tests: hyponeophagia, marble burying, elevated plus maze, open field, and the light and dark box. On the last day, we used a restraint test of 30 min duration and measured their stress reactivity by assaying plasma corticosterone. In the open field and the elevated plus-maze, we found that FRW mice behaved similarly to AL and ALW mice whereas FR mice did not express anxiety-like behaviour. The FRW mice displayed the lowest latency to reach the food in the hyponeophagia test. Regarding stress reactivity, FRW mice exhibited corticosterone reactivity after acute stress that was similar to the control mice, while FR mice did not fully return to basal corticosterone at one hour after the restraint stress. Taken together, these data demonstrate a differential reactivity to acute stress in FR conditions and a beneficial effect of running wheel activity in ALW and FRW conditions. Moreover, we report the absence of a typical anxiety-like behaviour associated with the food restriction (FR and FRW groups). We conclude that this model (FR and FRW mice) did not express typical anxiety-like behaviour, but that physical activity linked to food restriction improved coping strategies in an anxiogenic context.

Assessment of soluble epoxide hydrolase activity in vivo: A metabolomic approach.

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.

Plasma levels of one-carbon metabolism nutrients in women with anorexia nervosa.

OBJECTIVE: People who are ill with anorexia nervosa (AN) show altered availability of key plasma nutrients. However, little is known about the patterning of alterations that occurs across diverse nutrients during active phases of illness or about the persistence of any such alterations following remission of illness. METHOD: We compared plasma levels of one-carbon metabolism nutrients across women with active AN (AN-Active: n = 53), in remission from AN (AN-Remitted: n = 40), or who had no eating-disorder history (NED: n = 36). We also tested associations between body mass index (BMI) changes and changes in pre- to posttreatment nutrient levels, and explored the association between nutrient levels, on the one hand, and BMI and eating symptoms, on the other. Choline, betaine, and methionine were analyzed using mass spectrometry. Folate and B12 were analyzed using the AccuBind® ELISA kit. Eating-disorder symptoms were assessed by interview and self-report. RESULTS: Compared to NED individuals, AN-Active individuals exhibited significantly elevated B12 and (less-reliably) betaine. In AN-Active individuals, lower BMI was associated with higher B12. DISCUSSION: The observed alterations run contrary to the intuition that plasma nutrient levels should be directly responsive to nutritional status and suggest, instead, the existence of compensatory adaptations to malnutrition in individuals with active AN. Further study is required to clarify mechanisms that underlie such effects.

Altered circulating endocannabinoids in anorexia nervosa during acute and weight-restored phases: A pilot study.

Anorexia nervosa (AN) is an eating disorder characterized by a low food intake and often exceeding exercise, leading to a particularly low body × weight proportion. Patients with AN usually report less hunger than healthy controls. Endogenous endocannabinoids (eCBs), specifically the anandamide, have been associated to hunger, as a meal initiator, but research regarding AN and eCB and inconclusive. In this pilot study, we investigated plasma levels of eCB in inpatients with AN during fasting and after eating, both during the acute AN phase and after weight recovery. After an 8-hr fasting period, blood sample was collected from all participants. After that, participants were given a muffin test meal. Blood samples for the investigation of endogenous eCBs anandamide (N-arachidonoylethanolamide [AEA]) and 2-arachidonoylglycerol (2-AG) were then collected after 120 and 240 min. Participants were only allowed to eat and drink what was offered them during the research. AN reported less hunger than controls during fasting and at the end of the experiment. Also, plasma levels of AEA were significantly smaller in AN in comparison with controls in all time points. No significant difference was found for 2-AG plasma levels. After recovery, no significant difference was found for eCB levels. These findings could be interpreted as an AEA deregulation in AN before and after food intake, which persists after weight recovery. These findings may have implications to the pharmacological treatment of AN and to relapse occurring in the disorder.

Relationship between serum level of growth differentiation factors 8, 11 and bone mineral density in girls with anorexia nervosa.

BACKGROUND: Adolescents with anorexia nervosa (AN) have low body mass and low bone mineral density (BMD). Growth differentiation factor 8 (Myostatin, GDF8) and its homologue growth differentiation factor 11 (GDF11), members of the TGF-ß super-family, play an important role in muscle regeneration and bone metabolism in healthy individuals. However, their association with BMD in AN is unknown. The present study was undertaken to investigate the relationship between GDF8, GDF11 and BMD in adolescent girls with AN. METHODS: Serum GDF8, GDF11 and BMD were determined in 25 girls (12-16 years old) with AN and 31 healthy girls (12-16 years old). RESULTS: Growth differentiation factor 8 levels were lower in AN subjects. On the contrary, GDF11 levels were higher in AN subjects than controls. There was no relationship between GDF8 and BMD. A significant negative correlation between GDF11 and BMD was found. In multiple linear stepwise regression analysis, BMI, 25-hydroxyvitamin D, GDF11, or lean mass, but not fat mass and GDF8, were independent predictors of BMD in the AN and control groups separately. CONCLUSIONS: Growth differentiation factor 11 was independent predictor of BMD in girls with AN. It suggested that GDF11 exerts a negative effect on bone mass.

Increased lipid and lipoprotein concentrations in anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted a systematic review and a meta-analysis to evaluate changes in lipid concentrations in acutely-ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration. METHOD: A systematic literature review and meta-analysis (PROSPERO: CRD42017078014) were conducted for original peer-reviewed articles. RESULTS: Forty-eight studies were eligible for review; 33 for meta-analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high-density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low-density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely-ill AN than HC. Partially weight-restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre- versus post-weight restoration differences in lipid concentrations did not differ significantly. DISCUSSION: We report aggregate evidence for elevated lipid concentrations in acutely-ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta-analyses were limited by the number of available studies.

OBJETIVO: En la anorexia nervosa (AN) han sido reportadas alteraciones en las concentraciones de lípidos sanguíneos; sin embargo, la extensión, mecanismo y normalización con la restauración del peso continúa aún desconocida. Hicimos una revisión sistemática y meta-análisis para evaluar los cambios en las concentraciones de lípidos en pacientes agudamente enfermas de AN comparados con controles sanos (HC) y para examinar el efecto parcial de la restauración de peso. MÉTODO: Una revisión sistemática de la literatura y meta-análisis (PROSPERO: CRD42017078014) fueron llevados a cabo en artículos originales revisados por pares. RESULTADOS: Un total de cuarenta y ocho estudios fueron elegibles para revisión; 33 para meta-análisis calculando las diferencias promedio (MD). Colesterol total (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), lipoproteína de alta densidad (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), lipoproteína de baja densidad (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglicéridos (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), y apolipoproteína B (Apo B; MD = 11.6 mg/dL, CI = 2.3, 21.2) fueron significativamente elevados en los pacientes agudamente enfermos de AN en comparación con los controles sanos (HC). Los pacientes con AN parcialmente recuperados de peso tuvieron niveles más elevados de colesterol total (MD = 14.8 mg/dL, CI = 2.1, 27.5) y de LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Las diferencias pre- versus post- restauración de peso en las concentraciones de lípidos no difirieron significativamente. DISCUSIÓN: Reportamos evidencia agregada de concentraciones elevadas de lípidos en pacientes agudamente enfermos de AN comparados con controles sanos (HC), algunos de los cuales persisten después de la restauración parcial de peso. Esto podría señalar una adaptación subyacente o desregulación no completamente revertida por la restauración del peso. Aunque las concentraciones difirieron entre AN y HC, la mayoría de las concentraciones de lípidos permanecieron dentro del rango de referencia y los meta-análisis fueron limitados por el número de estudios disponibles.

Hemostasis at Extremes of Body Weight.

Extremes of body weight are not uncommon in the modern world and include anorexia nervosa (AN) and obesity. Both conditions are associated with increased morbidity and mortality: AN has the highest mortality rate of all mental illnesses and unfortunately obesity has reached epidemic proportions and is a well-recognized risk factor for cardiovascular disease including venous thromboembolism (VTE). This article summarizes the current understanding of hemostatic changes of these extremes of body weight. The hemostatic changes of AN have not been well described. Severe AN is associated with pancytopenia with decreased bone marrow cellularity, which causes a mild thrombocytopenia. Platelet hyperaggregability has been recognized in AN and has been attributed at least in part to increased adrenoceptor density. Obesity and the metabolic syndrome are associated with prothrombotic changes, which have been well characterized and related to complex adipocyte-induced inflammatory changes, including increased levels of plasminogen activator inhibitor type 1, von Willebrand factor, fibrinogen, and other evidence of increased coagulation and platelet activation. Accumulating evidence suggests a significant role for increased tissue factor expression and signaling in this relationship, with increased tissue factor expression present in adipose and possibly systemic tissues, induced by adipose-generated cytokines. Intriguingly, the hemostatic changes do not seem to increase with increasing BMI, although the risk of VTE increases with BMI, suggesting that decreased venous flow due to venous enlargement may play the most important role in increased VTE risk with obesity.

Prospective, randomized, double-blind, placebo-controlled phase IIa clinical trial on the effects of an estrogen-progestin combination as add-on to inpatient psychotherapy in adult female patients suffering from anorexia nervosa.

BACKGROUND: There is a need for novel treatment approaches in anorexia nervosa (AN). While there is broad knowledge with regard to altered appetite regulation and neuropsychological deficits in AN patients on the one hand, and the effects of estrogen replacement upon neuropsychological performance in healthy subjects on the other, up to now, no study has implemented estrogen replacement in AN patients, in order to examine its effects upon AN-associated and general psychopathology, neuropsychological performance and concentrations of peptide components of the hypothalamus-pituitary-adrenal (HPA) axis and within appetite-regulating circuits. METHODS: This is a randomized placebo-controlled clinical trial on the effects of a 10-week oral estrogen replacement (combination of ethinyl estradiol 0.03 mg and dienogest 2 mg) in adult female AN patients. The primary target is the assessment of the impact of sex hormone replacement upon neuropsychological performance by means of a neuropsychological test battery consisting of a test for verbal intelligence, the Trail making test A and B, a Go/No-go paradigm with food cues and the Wisconsin Card Sorting Test. Secondary targets include a) the examination of safety and tolerability (as mirrored by the number of adverse events), b) assessments of the impact upon eating disorder-specific psychopathology by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2), c) the influence upon anxiety using the State-Trait-Anxiety Inventory (STAI), d) assessments of plasma cortisol levels during a dexamethasone-suppression test and appetite-regulating plasma peptides (ghrelin, leptin, insulin, glucose) during an oral glucose tolerance test and, e) a possible impact upon the prescription of antidepressants. DISCUSSION: This is the first study of its kind. There are no evidence-based psychopharmacological options for the treatment of AN. Thus, the results of this clinical trial may have a relevant impact on future treatment regimens. Novel approaches are necessary to improve rates of AN symptom remission and increase the rapidity of treatment response. Identifying the underlying biological (e.g. neuroendocrinological) factors that maintain AN or may predict patient treatment response represent critical future research directions. Continued efforts to incorporate novel pharmacological aspects into treatments will increase access to evidence-based care and help reduce the burden of AN. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2015-004184-36, registered November 2015; ClinicalTrials.gov Identifier: NCT03172533 , retrospectively registered May 2017.

Directly measured free 25-hydroxy vitamin D levels show no evidence of vitamin D deficiency in young Swedish women with anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is an eating disorder characterized by low fat mass complicated by osteoporosis. The role of circulating vitamin D in the development of bone loss in AN is unclear. Fat mass is known to be inversely associated with vitamin D levels measured as serum levels of total, protein-bound 25-hydroxyvitamin D, but the importance of directly measured, free levels of 25(OH)D has not been determined in AN. The aim of this study was to investigate vitamin D status, as assessed by serum concentrations of total and free serum 25(OH)D in patients with AN and healthy controls. METHODS: In female AN patients (n = 20), and healthy female controls (n = 78), total 25(OH)D was measured by LC-MS/MS, and free 25(OH)D with ELISA. In patients with AN bone mineral density (BMD) was determined with DEXA. RESULTS: There were no differences between patients and controls in total or free S-25(OH)D levels (80 ± 31 vs 72 ± 18 nmol/L, and 6.5 ± 2.5 vs 5.6 ± 1.8 pg/ml, respectively), and no association to BMD was found. In the entire group of patients and controls, both vitamin D parameters correlated with BMI, leptin, and PTH. CONCLUSIONS: The current study did not demonstrate a vitamin D deficiency in patients with AN and our data does not support vitamin D deficiency as a contributing factor to bone loss in AN. Instead, we observed a trend toward higher vitamin D levels in AN subjects compared to controls. Measurement of free vitamin D levels did not contribute to additional information.

[Serum kisspeptin levels in patients with anorexia nervosa]. / Stezenia kisspeptyny w surowicy u chorych z rozpoznanym jadlowstretem psychicznym.

Anorexia nervosa (AN) is a disorder characterized by extreme restriction of food intake and incorrect perception of patients' body, its weight and shape. Patients diagnosed with anorexia nervosa apart from an eating disorder are characterized also by hypothalamic amenorrhea. Many neuropeptides and neurotransmitters play an important role in physiological regulation of gonadoliberin (GnRH) secretion. AIM: The aim of the study is to assess the role of kisspeptin in the etiology of anorexia nervosa. MATERIALS AND METHODS: The study was classified as 55 women aged from 17 to 28 years old. Patients were classified into two groups: study group consisted of 15 patients diagnosed with AN and control group consisted of 40 healthy women. Examination of serum blood from patients was performed by ELISA-enzyme-linked immunosorbent assay. Concentrations of serum kisspeptin, FSH, LH, estradiol, prolactin, testosterone were analyzed in patients from study and control group. RESULTS: The average body weight of patients with AN was 45.0±7.56 kg and was statistically significantly lower compared to women in the control group (61.1±7.20 kg) (p=0.0001). The average serum concentration of kisspeptin in patients with AN was 0.20±0.07 ng/ml, in women in the control group was 0.3±0.36 ng/ml (p=0.712). Serum LH concentrations in patients with AN was 2.5±1.71 mIU/ml and was statistically significantly lower compared to women in the control group (13.5±9.73 mIU/ml) (p=0.0001). The mean serum estradiol concentrations in patients with AN were 31.0±15.3 pg/ml and were statistically significantly lower compared to the control group (129.0±107.7 pg/ml) (p=0.0001). CONCLUSIONS: There was not significant difference between serum kisspeptin levels in patients with AN and healthy women. Further research is needed on the role of kisspeptin in AN.

Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa.

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.

Vitamin D status in young Swedish women with anorexia nervosa during intensive weight gain therapy.

PURPOSE: Anorexia nervosa (AN) is associated with reduced bone mass and an increased fracture risk. The aim was to evaluate the vitamin D status and the association with body mass index (BMI), fat mass and bone mineral density (BMD) in patients with severe AN during a prospective intervention study of intensive nutrition therapy. METHODS: This study comprised 25 Swedish female AN patients (20.1 ± 2.3 years), who were treated as inpatients for 12 weeks with a high-energy diet. Serum 25-hydroxyvitamin D (25(OH)D), calcium, phosphate and parathyroid hormone (PTH) were measured. BMD and body composition were assessed by dual-energy X-ray absorptiometry at study start and after 12 weeks. RESULTS: Twenty-two patients completed the study. The mean weight gain was 9.9 kg and BMI (mean ± SD) increased from 15.5 ± 0.9 to 19.0 ± 0.9 kg/m2, P < 0.0001. Fat mass increased from median 12 to 27 %. The median serum 25(OH)D level was 84 nmol/L at baseline, which decreased to 76 nmol/L, P < 0.05. PTH increased from median 21.9 to 30.0 ng/L, P < 0.0001. BMC increased during the study period, P < 0.001. CONCLUSIONS: Serum 25(OH)D levels were adequate both at study start and completion, however, nominally decreased after the 12-week nutritional intervention. PTH increased subsequently, which coincide with the decreased 25(OH)D levels. The reduction in 25(OH)D could be due to an increased storage of vitamin D related to the increase in fat mass since vitamin D is sequestered in adipose tissue.

Association between antipsychotic treatment and leptin levels across multiple psychiatric populations: An updated meta-analysis.

OBJECTIVE: Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls. METHOD: Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model. RESULTS: Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001). CONCLUSION: Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses.