Psychoneuroendocrinology (2015) 53, 127—135
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Serum visfatin concentration in acutely ill and weight-recovered patients with anorexia nervosa Maria Seidel a, Joseph A. King a, Franziska Ritschel a, Johanna Döpmann b, Katharina Bühren c, Jochen Seitz c, Veit Roessner a, Sabine Westphal d, Karin Egberts e, Roland Burghardt b, Christoph Wewetzer f, Christian Fleischhaker g, Johannes Hebebrand h, Beate Herpertz-Dahlmann c, Stefan Ehrlich a,∗ a
Department of Child and Adolescent Psychiatry, Eating Disorder Services and Research Center, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Fetscherstrasse 74, 01307 Dresden, Germany b Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany c Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Aachen, RWTH University, Neuenhofer Weg 21, 52074 Aachen, Germany d Institute of Clinical Chemistry, Magdeburg University Hospital, Leipziger Strasse 44, 39120 Magdeburg, Germany e Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, University Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany f Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Cologne, University Cologne, Robert-Koch-Strasse 10, 50931 Cologne, Germany g Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University Hospital Freiburg, University Freiburg, Hauptstrasse 8, 79104 Freiburg, Germany h Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Duisburg-Essen, Wickenburgstrasse 21, 45147 Essen, Germany Received 19 July 2014; received in revised form 11 December 2014; accepted 11 December 2014
KEYWORDS Visfatin; Anorexia nervosa;
Summary Visfatin is a recently described protein that is thought to regulate the process of adipocyte differentiation. Findings suggest that visfatin may be actively involved in the control of weight regulatory networks. However, to what extent and which role it plays in
∗ Corresponding author at: Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Fetscherstraße 74, 01307 Dresden, Germany. Tel.: +49 0351 458 2244; fax: +49 0351 458 5754. E-mail address: [email protected] (S. Ehrlich).
http://dx.doi.org/10.1016/j.psyneuen.2014.12.010 0306-4530/© 2015 Elsevier Ltd. All rights reserved.
128
Weight recovered anorexia nervosa; Adipokines; Leptin
M. Seidel et al. eating disorders is still poorly understood, as mixed results have been reported. The aim of the current study was to investigate serum visfatin concentrations on a cross sectional sample between acute anorexia nervosa patients (n = 44), weight recovered patients (n = 13) and healthy controls (n = 46) and a longitudinal sample of acute patients (n = 57) during weight recovery at three different time-points. Results did not show significant differences in visfatin between the three groups; however, acute patients showed a higher visfatin/BMI-SDS ratio than controls and recovered patients. Longitudinal results revealed an increase of visfatin levels during therapy. Our results suggest that high ratios of visfatin/BMI-SDS could be a state marker in acute anorexia nervosa, displaying a compensatory mechanism of the individual to maintain normal visfatin levels under malnourished conditions. © 2015 Elsevier Ltd. All rights reserved.
1. Introduction Adipokines play a central role in the control of energy metabolism. They provide signals about the nutrient status of an organism, such as energy intake and expenditure as well as insulin sensitivity (Badman and Flier, 2007) and have therefore become a matter of central interest in the field of eating disorder research. Over the last years, particular attention has been paid to the role of leptin (Ehrlich et al., 2009; Föcker et al., 2011; Hebebrand et al., 2007). In contrast, our knowledge of the novel adipokine visfatin is still sparse. Visfatin appears to be a multifunctional protein, acting as hormone, cytokine, and enzyme (for a review, see Sonoli et al., 2011). It was firstly identified as a Pre-B Cell Colony-Enhancing Factor (PBEF; Samal et al., 1994), which facilitated the maturation of early Blymphocytes. It was also found to act as an enzyme called nicotinamide phosphoribosyl transferase (NAMPT), which is involved in the nicotine adenine dinucleotide (NAD+) salvage pathway. In 2005, Fukuhara et al. demonstrated that the adipokine visfatin, which amino acid sequence was identical to NAMPT/PBEF, acted as a protein mediator secreted by fat cells. It appears that visfatin secretion increases in the course of adipocyte differentiation and its synthesis is regulated by several factors including glucocorticoids, tumor necrosis factor alpha, interleukin 6, and growth factor hormone (Jia et al., 2004). Although the role of visfatin in energy homeostasis or weight regulation is of particular interest with respect to eating disorders and diabetes, reported results have been very heterogeneous, as highlighted in Table 1. Several studies have demonstrated elevated visfatin levels both in obese adults (Auguet et al., 2013; Jin et al., 2008; Manco et al., 2007; Pagano et al., 2006; Terra et al., 2012; Wen et al., 2012) and children (Davutoglu et al., 2009; Dogru et al., 2007; Pagano et al., 2006; Revollo et al., 2004; Sandeep et al., 2007) as well as in patients with diabetes mellitus (Chen et al., 2006; Dogru et al., 2007; Pagano et al., 2006; Revollo et al., 2004; Sandeep et al., 2007), suggesting a possible link to insulin and glucose homeostasis. Further investigations found visfatin to be closely correlated with white adipose tissue (WAT) accumulation (Curat et al., 2006; Jia et al., 2004). However, initial reports that visfatin is preferentially expressed by visceral adipose tissue (VAT; Araki et al., 2008; Barth et al., 2010; Fukuhara et al., 2005) could not be confirmed by other studies (Berndt et al., 2005; Haider et al., 2006a; Körner et al., 2007).
Similarly heterogeneous results were reported from studies testing for associations between visfatin levels and BMI in healthy individuals. Some authors found positive correlations while others found no relationship at all (see Table 1). Equally mixed results were observed in obese samples (Pagano et al., 2006; Ziora et al., 2012). Important for eating disorder research are also notions of visfatin sharing associations with thyroid hormones (Caixàs et al., 2009; Ozkaya et al., 2009) as well as bone formation (Xie et al., 2007), steroid hormone synthesis and ovarian functioning (Chan et al., 2007; Reverchon et al., 2013; Tsouma et al., 2014; Zhang et al., 2014), however, results are again quite heterogeneous. These inconsistent findings may be partly due to the fact that researchers have not applied standard laboratory procedures, i.e. studies have used either serum or plasma samples and employed different immunoassays (see Table 1). According to a recent study (Körner et al., 2007) some of these immunoassays may deliver erroneous results due to unspecific binding. Research investigating visfatin under catabolic conditions has been rare. Reduced dietary intake (De Luis et al., 2008; Haider et al., 2006b; Manco et al., 2007; Martos-Moreno et al., 2011) as well as exercise (Choi et al., 2007) have been associated with reduced visfatin concentrations in some but not all studies (Kang et al., 2011). Insights into the role of visfatin as an adipokine in weight disorders and its function in metabolic processes might be gained by investigating visfatin levels in anorexia nervosa (AN), a severe illness characterized by markedly reduced calorie intake and fear of weight gain leading to a significant decrease in overall adipose tissue (Treasure and Schmidt, 2005). To date, only two studies have investigated visfatin levels in AN — again with mixed results (see Table 1). Both used a cross-sectional design and applied an Enzyme Immunoassay (EIA; Phoenix Pharmaceuticals Inc., USA), which according to Körner et al. (2007) may have limited performance due to non-specific binding. Longitudinal data and data from recovered AN patients are still missing. The aim of the current study was to investigate visfatin levels in patients with acute AN, recovered from AN as well as longitudinally, using the only immunoassay (ELISA) that has been shown to measure serum visfatin with an acceptable specificity (Körner et al., 2007), with the overarching goal of establishing the potential clinical utility of visfatin as an endocrine biomarker in AN.
Serum visfatin in anorexia nervosa
129
Table 1 Visfatin research on weight related disorders. The table shows differences in visfatin between studied groups, whether visfatin in the sample showed a correlation with BMI, the used immunoassay, and type of blood sample. Author, year
Group comparison
Correlation with BMI
Assay
Araki et al., 2008 Auguet et al., 2013 Dogru et al., 2007 Dostálová et al., 2009 Davutoglu et al., 2009
HC < OB HC < OB HC < D HC = AN HC < OB
ELISA ELISA ELISA EIA ELISA
Körner et al., 2007 Martos-Moreno et al., 2011 Miazgowski et al., 2013
HC = OB HC < OB
No Not reported No Not reported No in HC Yes (+) in Ob No Yes (+)
ELISA c EIA
Serum Serum
HC = normal weight OB HC = OB
No
EIA
Serum
No
ELISA b
Plasma
HC > OB HC < OB
EIA ELISA c
Plasma Serum
HC > OB HC < OB
Yes (−) No before weight loss Yes after weight loss NO NO
ELISA e EIA
Plasma Serum
HC > AN/NOS HC < OB
Yes (+) in HC Yes (−) in OB
EIA
Serum
Olszanecka-Glinianowicz et al., 2012 Pagano et al., 2006 Terra et al., 2012
Wen et al., 2012 Zahorska-Markiewicz et al., 2007 Ziora et al., 2012
Serum/plasma a, b c b d
Plasma Serum Plasma Serum Plasma
HC = healthy control group; OB = obesity; AN = anorexia nervosa; D = diabetes mellitius; EIA = enzyme immune assay; ELISA = enzyme linked immunosorbent assay. ELISA a = RD Systems, Minneapolis, MN; ELISA b = Phoenix Pharmaceuticals, Belmont, CA/USA; ELISA c = AdipoGen Inc., Seoul, Korea; ELISA d = Alpco Diagnostics, Salem, NH; ELISA e = HuameiBio Inc., Wuhan, China. (—) = negative assocation; (+) = positive association.
2. Methods 2.1. Participants The study population consisted of two independent samples. Sample [A] was drawn from the child and adolescent psychiatry and psychosomatic medicine treatment programs at Charité-Universitätsmedizin Berlin between 2006 and 2010 and included 46 female subjects with acute AN according to DSM-IV (acAN), 13 weight recovered patients (recAN) and 48 normal-weight, healthy female controls (HC). Participants in sample [B] were part of a multicenter study (2007 and 2011) funded by the German Ministry for Education and Research (for study details see Herpertz-Dahlmann et al., 2014) which included 63 adolescent first episode acAN, with assessment time points at admission (T1), at discharge (T2, mean = 18.53 (3—49) weeks) and at a follow-up (independent of rehabilitation status) 52 weeks after admission (T3, mean = 53.0 weeks) and corresponding clinical and endocrinological data (per protocol approach). Between T1 and T2 in sample [B], all acAN were enrolled in a behaviorally oriented nutritional rehabilitation program (in an inpatient or day-patient setting) and were encouraged to gain a minimum of 500—800 g of body weight weekly (for details see supplementary Appendix 1). Between T2 and T3 all subjects were treated as outpatients.
To be considered ‘‘recovered’’, recAN subjects in sample [A] had to, for at least 6 months: (1) maintain a BMI > 18.5 (if older than 18 years) or a BMI > 10th BMI percentile (if younger than 18 years), (2) menstruate, and (3) have not binged, purged, or engaged in significant restrictive eating patterns. All recAN participant in sample [A] were weight recovered for longer than 1 year with the exception of one participant who was weight recovered between 6 and 12 months. The control group consisted of normal-weight, eumenorrheic, healthy participants who we recruited through advertisement among middle school, high school, and university students. Exclusion criteria and possible confounding variables, including menstrual cycle, and use of contraceptive medication were obtained using a semi structured research interview, the SIAB-EX interview (see below) and our own research interview. Comorbid psychiatric diagnoses other than eating disorders were derived from medical records. HC were excluded, if they reported any history of psychiatric illness. Patients were omitted if they had a lifetime history of any of the following diagnoses: organic brain syndrome, schizophrenia, substance dependence, bipolar illness, bulimia nervosa, or binge eating disorder. Further exclusion criteria for all participants were IQ less than 85, current inflammatory, neurological or metabolic illness, anemia, pregnancy, breast feeding, and consumption of substances and psychotropic medication within the past 6 weeks
AcAN = acute anorexia patients, recAN = recovered anorexia patients, HC = healthy controls, BMI-SDS = body mass index standard deviation score, EDI-2 = Eating Disorder Inventory. Age is given in years, BMI in kg/m2 , Visfatin in ng/ml and visfatin/BMI-SDS in (ng/ml)/SDS, leptin in g/l, leptin-SDS in (g/l)/SDS.
13.00 recAN acAN > HCW 0.18 ± 0.09 (0.06—0.56) 0.25 ± 0.15 (0.05—2.69) (44/13/46)
0.15 ± 0.09 (0.05—0.78)
— 0.744 — 0.30 0.91 ± 0.61 (0.23—2.94) 1.05 ± 0.46 (0.31—1.74) 0.9 ± 0.54 (0.14—2.47) (44/13/46)
acAN < recAN acAN < recAN acAN > recAN acAN < recAN acAN < recAN
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/psyneuen
Serum visfatin concentration in acutely ill and weight-recovered patients with anorexia nervosa Maria Seidel a, Joseph A. King a, Franziska Ritschel a, Johanna Döpmann b, Katharina Bühren c, Jochen Seitz c, Veit Roessner a, Sabine Westphal d, Karin Egberts e, Roland Burghardt b, Christoph Wewetzer f, Christian Fleischhaker g, Johannes Hebebrand h, Beate Herpertz-Dahlmann c, Stefan Ehrlich a,∗ a
Department of Child and Adolescent Psychiatry, Eating Disorder Services and Research Center, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Fetscherstrasse 74, 01307 Dresden, Germany b Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany c Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Aachen, RWTH University, Neuenhofer Weg 21, 52074 Aachen, Germany d Institute of Clinical Chemistry, Magdeburg University Hospital, Leipziger Strasse 44, 39120 Magdeburg, Germany e Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, University Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany f Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Cologne, University Cologne, Robert-Koch-Strasse 10, 50931 Cologne, Germany g Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University Hospital Freiburg, University Freiburg, Hauptstrasse 8, 79104 Freiburg, Germany h Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Duisburg-Essen, Wickenburgstrasse 21, 45147 Essen, Germany Received 19 July 2014; received in revised form 11 December 2014; accepted 11 December 2014
KEYWORDS Visfatin; Anorexia nervosa;
Summary Visfatin is a recently described protein that is thought to regulate the process of adipocyte differentiation. Findings suggest that visfatin may be actively involved in the control of weight regulatory networks. However, to what extent and which role it plays in
∗ Corresponding author at: Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Fetscherstraße 74, 01307 Dresden, Germany. Tel.: +49 0351 458 2244; fax: +49 0351 458 5754. E-mail address: [email protected] (S. Ehrlich).
http://dx.doi.org/10.1016/j.psyneuen.2014.12.010 0306-4530/© 2015 Elsevier Ltd. All rights reserved.
128
Weight recovered anorexia nervosa; Adipokines; Leptin
M. Seidel et al. eating disorders is still poorly understood, as mixed results have been reported. The aim of the current study was to investigate serum visfatin concentrations on a cross sectional sample between acute anorexia nervosa patients (n = 44), weight recovered patients (n = 13) and healthy controls (n = 46) and a longitudinal sample of acute patients (n = 57) during weight recovery at three different time-points. Results did not show significant differences in visfatin between the three groups; however, acute patients showed a higher visfatin/BMI-SDS ratio than controls and recovered patients. Longitudinal results revealed an increase of visfatin levels during therapy. Our results suggest that high ratios of visfatin/BMI-SDS could be a state marker in acute anorexia nervosa, displaying a compensatory mechanism of the individual to maintain normal visfatin levels under malnourished conditions. © 2015 Elsevier Ltd. All rights reserved.
1. Introduction Adipokines play a central role in the control of energy metabolism. They provide signals about the nutrient status of an organism, such as energy intake and expenditure as well as insulin sensitivity (Badman and Flier, 2007) and have therefore become a matter of central interest in the field of eating disorder research. Over the last years, particular attention has been paid to the role of leptin (Ehrlich et al., 2009; Föcker et al., 2011; Hebebrand et al., 2007). In contrast, our knowledge of the novel adipokine visfatin is still sparse. Visfatin appears to be a multifunctional protein, acting as hormone, cytokine, and enzyme (for a review, see Sonoli et al., 2011). It was firstly identified as a Pre-B Cell Colony-Enhancing Factor (PBEF; Samal et al., 1994), which facilitated the maturation of early Blymphocytes. It was also found to act as an enzyme called nicotinamide phosphoribosyl transferase (NAMPT), which is involved in the nicotine adenine dinucleotide (NAD+) salvage pathway. In 2005, Fukuhara et al. demonstrated that the adipokine visfatin, which amino acid sequence was identical to NAMPT/PBEF, acted as a protein mediator secreted by fat cells. It appears that visfatin secretion increases in the course of adipocyte differentiation and its synthesis is regulated by several factors including glucocorticoids, tumor necrosis factor alpha, interleukin 6, and growth factor hormone (Jia et al., 2004). Although the role of visfatin in energy homeostasis or weight regulation is of particular interest with respect to eating disorders and diabetes, reported results have been very heterogeneous, as highlighted in Table 1. Several studies have demonstrated elevated visfatin levels both in obese adults (Auguet et al., 2013; Jin et al., 2008; Manco et al., 2007; Pagano et al., 2006; Terra et al., 2012; Wen et al., 2012) and children (Davutoglu et al., 2009; Dogru et al., 2007; Pagano et al., 2006; Revollo et al., 2004; Sandeep et al., 2007) as well as in patients with diabetes mellitus (Chen et al., 2006; Dogru et al., 2007; Pagano et al., 2006; Revollo et al., 2004; Sandeep et al., 2007), suggesting a possible link to insulin and glucose homeostasis. Further investigations found visfatin to be closely correlated with white adipose tissue (WAT) accumulation (Curat et al., 2006; Jia et al., 2004). However, initial reports that visfatin is preferentially expressed by visceral adipose tissue (VAT; Araki et al., 2008; Barth et al., 2010; Fukuhara et al., 2005) could not be confirmed by other studies (Berndt et al., 2005; Haider et al., 2006a; Körner et al., 2007).
Similarly heterogeneous results were reported from studies testing for associations between visfatin levels and BMI in healthy individuals. Some authors found positive correlations while others found no relationship at all (see Table 1). Equally mixed results were observed in obese samples (Pagano et al., 2006; Ziora et al., 2012). Important for eating disorder research are also notions of visfatin sharing associations with thyroid hormones (Caixàs et al., 2009; Ozkaya et al., 2009) as well as bone formation (Xie et al., 2007), steroid hormone synthesis and ovarian functioning (Chan et al., 2007; Reverchon et al., 2013; Tsouma et al., 2014; Zhang et al., 2014), however, results are again quite heterogeneous. These inconsistent findings may be partly due to the fact that researchers have not applied standard laboratory procedures, i.e. studies have used either serum or plasma samples and employed different immunoassays (see Table 1). According to a recent study (Körner et al., 2007) some of these immunoassays may deliver erroneous results due to unspecific binding. Research investigating visfatin under catabolic conditions has been rare. Reduced dietary intake (De Luis et al., 2008; Haider et al., 2006b; Manco et al., 2007; Martos-Moreno et al., 2011) as well as exercise (Choi et al., 2007) have been associated with reduced visfatin concentrations in some but not all studies (Kang et al., 2011). Insights into the role of visfatin as an adipokine in weight disorders and its function in metabolic processes might be gained by investigating visfatin levels in anorexia nervosa (AN), a severe illness characterized by markedly reduced calorie intake and fear of weight gain leading to a significant decrease in overall adipose tissue (Treasure and Schmidt, 2005). To date, only two studies have investigated visfatin levels in AN — again with mixed results (see Table 1). Both used a cross-sectional design and applied an Enzyme Immunoassay (EIA; Phoenix Pharmaceuticals Inc., USA), which according to Körner et al. (2007) may have limited performance due to non-specific binding. Longitudinal data and data from recovered AN patients are still missing. The aim of the current study was to investigate visfatin levels in patients with acute AN, recovered from AN as well as longitudinally, using the only immunoassay (ELISA) that has been shown to measure serum visfatin with an acceptable specificity (Körner et al., 2007), with the overarching goal of establishing the potential clinical utility of visfatin as an endocrine biomarker in AN.
Serum visfatin in anorexia nervosa
129
Table 1 Visfatin research on weight related disorders. The table shows differences in visfatin between studied groups, whether visfatin in the sample showed a correlation with BMI, the used immunoassay, and type of blood sample. Author, year
Group comparison
Correlation with BMI
Assay
Araki et al., 2008 Auguet et al., 2013 Dogru et al., 2007 Dostálová et al., 2009 Davutoglu et al., 2009
HC < OB HC < OB HC < D HC = AN HC < OB
ELISA ELISA ELISA EIA ELISA
Körner et al., 2007 Martos-Moreno et al., 2011 Miazgowski et al., 2013
HC = OB HC < OB
No Not reported No Not reported No in HC Yes (+) in Ob No Yes (+)
ELISA c EIA
Serum Serum
HC = normal weight OB HC = OB
No
EIA
Serum
No
ELISA b
Plasma
HC > OB HC < OB
EIA ELISA c
Plasma Serum
HC > OB HC < OB
Yes (−) No before weight loss Yes after weight loss NO NO
ELISA e EIA
Plasma Serum
HC > AN/NOS HC < OB
Yes (+) in HC Yes (−) in OB
EIA
Serum
Olszanecka-Glinianowicz et al., 2012 Pagano et al., 2006 Terra et al., 2012
Wen et al., 2012 Zahorska-Markiewicz et al., 2007 Ziora et al., 2012
Serum/plasma a, b c b d
Plasma Serum Plasma Serum Plasma
HC = healthy control group; OB = obesity; AN = anorexia nervosa; D = diabetes mellitius; EIA = enzyme immune assay; ELISA = enzyme linked immunosorbent assay. ELISA a = RD Systems, Minneapolis, MN; ELISA b = Phoenix Pharmaceuticals, Belmont, CA/USA; ELISA c = AdipoGen Inc., Seoul, Korea; ELISA d = Alpco Diagnostics, Salem, NH; ELISA e = HuameiBio Inc., Wuhan, China. (—) = negative assocation; (+) = positive association.
2. Methods 2.1. Participants The study population consisted of two independent samples. Sample [A] was drawn from the child and adolescent psychiatry and psychosomatic medicine treatment programs at Charité-Universitätsmedizin Berlin between 2006 and 2010 and included 46 female subjects with acute AN according to DSM-IV (acAN), 13 weight recovered patients (recAN) and 48 normal-weight, healthy female controls (HC). Participants in sample [B] were part of a multicenter study (2007 and 2011) funded by the German Ministry for Education and Research (for study details see Herpertz-Dahlmann et al., 2014) which included 63 adolescent first episode acAN, with assessment time points at admission (T1), at discharge (T2, mean = 18.53 (3—49) weeks) and at a follow-up (independent of rehabilitation status) 52 weeks after admission (T3, mean = 53.0 weeks) and corresponding clinical and endocrinological data (per protocol approach). Between T1 and T2 in sample [B], all acAN were enrolled in a behaviorally oriented nutritional rehabilitation program (in an inpatient or day-patient setting) and were encouraged to gain a minimum of 500—800 g of body weight weekly (for details see supplementary Appendix 1). Between T2 and T3 all subjects were treated as outpatients.
To be considered ‘‘recovered’’, recAN subjects in sample [A] had to, for at least 6 months: (1) maintain a BMI > 18.5 (if older than 18 years) or a BMI > 10th BMI percentile (if younger than 18 years), (2) menstruate, and (3) have not binged, purged, or engaged in significant restrictive eating patterns. All recAN participant in sample [A] were weight recovered for longer than 1 year with the exception of one participant who was weight recovered between 6 and 12 months. The control group consisted of normal-weight, eumenorrheic, healthy participants who we recruited through advertisement among middle school, high school, and university students. Exclusion criteria and possible confounding variables, including menstrual cycle, and use of contraceptive medication were obtained using a semi structured research interview, the SIAB-EX interview (see below) and our own research interview. Comorbid psychiatric diagnoses other than eating disorders were derived from medical records. HC were excluded, if they reported any history of psychiatric illness. Patients were omitted if they had a lifetime history of any of the following diagnoses: organic brain syndrome, schizophrenia, substance dependence, bipolar illness, bulimia nervosa, or binge eating disorder. Further exclusion criteria for all participants were IQ less than 85, current inflammatory, neurological or metabolic illness, anemia, pregnancy, breast feeding, and consumption of substances and psychotropic medication within the past 6 weeks
AcAN = acute anorexia patients, recAN = recovered anorexia patients, HC = healthy controls, BMI-SDS = body mass index standard deviation score, EDI-2 = Eating Disorder Inventory. Age is given in years, BMI in kg/m2 , Visfatin in ng/ml and visfatin/BMI-SDS in (ng/ml)/SDS, leptin in g/l, leptin-SDS in (g/l)/SDS.
13.00 recAN acAN > HCW 0.18 ± 0.09 (0.06—0.56) 0.25 ± 0.15 (0.05—2.69) (44/13/46)
0.15 ± 0.09 (0.05—0.78)
— 0.744 — 0.30 0.91 ± 0.61 (0.23—2.94) 1.05 ± 0.46 (0.31—1.74) 0.9 ± 0.54 (0.14—2.47) (44/13/46)
acAN < recAN acAN < recAN acAN > recAN acAN < recAN acAN < recAN
