Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.
- MeSH
- Asijci genetika MeSH
- běloši genetika MeSH
- celogenomová asociační studie MeSH
- jaderné proteiny genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kalcineurin genetika MeSH
- kulinové proteiny genetika MeSH
- lidé MeSH
- mentální anorexie genetika MeSH
- metaanalýza jako téma MeSH
- studie případů a kontrol MeSH
- transportní proteiny genetika MeSH
- výměnné faktory guaninnukleotidů genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Japonsko MeSH
- Názvy látek
- CUL3 protein, human MeSH Prohlížeč
- FAM124B protein, human MeSH Prohlížeč
- jaderné proteiny MeSH
- kalcineurin MeSH
- kulinové proteiny MeSH
- PPP3CA protein, human MeSH Prohlížeč
- SPATA13 protein, human MeSH Prohlížeč
- transportní proteiny MeSH
- výměnné faktory guaninnukleotidů MeSH
Haem oxygenase 1 (HO-1) plays a pivotal role in metabolic stress protecting cells in dependence on reactive oxygen species. This study investigated a potential gene environment interaction between the (GT)n repeat HO1 polymorphism and the stress perception in patients with eating disorder and in controls. Stress perception and (GT)n polymorphism were measured in 127 patients with eating disorders and in 78 healthy controls using Stress and Coping Inventory and genotyping. Based on the inventory, overall, specific and weighted stress scores were defined. Clinical stress score was generated according to the patient's history and interviews. According to our hypothesis, 1) all stress scores describing subjective stress perception were significantly higher in patients compared to controls (P ≤ 0.001; P ≤ 0.002; P ≤ 0.001), 2) the L/L genotype of GT promoter repeats (L < 25 GT repeats, S < 25 GT repeats) in the patients was associated with higher overall (P ≤ 0.001), specific (P ≤ 0.010) and weighted stress score (P ≤ 0.005) compared to the L/S variant, and 3) Pearson's correlation of clinical versus objective stress scores showed not very tight relationship (0.198; 0.287; 0.224, respectively). We assume potential risk of the L allele of HO1 promoter polymorphism for the stress response and contribution of the subjective stress perception together with the L/L genotype to the development of eating disorder. Decreased HO1 expression in the presence of L/L genotype plus more intensive stress perception in the patients can lead to secondary stress, with increasing severity of the symptoms and aggravation of the disease.
- MeSH
- hemoxygenasa-1 genetika MeSH
- lidé MeSH
- poruchy příjmu potravy genetika psychologie MeSH
- promotorové oblasti (genetika) genetika MeSH
- psychický stres psychologie MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hemoxygenasa-1 MeSH
Preadipocyte factor-1 (Pref-1) is a member of epidermal growth-factor like family of proteins that regulates adipocyte and osteoblast differentiation. Experimental studies suggest that circulating Pref-1 levels may be also involved in the regulation of lipid and glucose metabolism and energy homeostasis. We hypothesized that alterations in Pref-1 levels may contribute to the ethiopathogenesis of anorexia nervosa or its underlying metabolic abnormalities. We measured Pref-1 concentrations and other hormonal, biochemical and anthropometric parameters in eighteen patients with anorexia nervosa and sixteen healthy women and studied the influence of partial realimentation of anorexia nervosa patients on these parameters. The mean duration of realimentation period was 46±2 days. At baseline, anorexia nervosa patients had significantly decreased body mass index, body weight, body fat content, fasting glucose, serum insulin, TSH, free T4, leptin and total protein. Partial realimentation improved these parameters. Baseline serum Pref-1 levels did not significantly differ between anorexia nervosa and control group (0.26±0.02 vs. 0.32±0.05 ng/ml, p=0.295) but partial realimentation significantly increased circulating Pref-1 levels (0.35±0.04 vs. 0.26±0.02 ng/ml, p<0.05). Post-realimentation Pref-1 levels significantly positively correlated with the change of body mass index after realimentation (r=0.49, p<0.05). We conclude that alterations in Pref-1 are not involved in the ethiopathogenesis of anorexia nervosa but its changes after partial realimentation could be involved in the regulation of adipose tissue expansion after realimentation.
- MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- inzulin krev MeSH
- leptin krev MeSH
- lidé MeSH
- membránové proteiny krev MeSH
- mentální anorexie metabolismus terapie MeSH
- mezibuněčné signální peptidy a proteiny krev MeSH
- mladý dospělý MeSH
- přijímání potravy fyziologie MeSH
- proteiny vázající vápník MeSH
- tělesná hmotnost fyziologie MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DLK1 protein, human MeSH Prohlížeč
- inzulin MeSH
- leptin MeSH
- membránové proteiny MeSH
- mezibuněčné signální peptidy a proteiny MeSH
- proteiny vázající vápník MeSH
Peptides ghrelin, obestatin and neuropeptide Y (NPY) play an important role in regulation of energy homeostasis, the imbalance of which is associated with eating disorders anorexia (AN) and bulimia nervosa (BN). The changes in ghrelin, obestatin and NPY plasma levels were investigated in AN and BN patients after administration of a high-carbohydrate breakfast (1604 kJ). Eight AN women (aged 25.4+/-1.9, BMI: 15.8+/-0.5), thirteen BN women (aged 22.0+/-1.05, BMI: 20.1+/-0.41) and eleven healthy women (aged 25.1+/-1.16, BMI: 20.9+/-0.40) were recruited for the study. We demonstrated increased fasting ghrelin in AN, but not in BN patients, while fasting obestatin and NPY were increased in both AN and BN patients compared to the controls. Administration of high-carbohydrate breakfast induced a similar relative decrease in ghrelin and obestatin plasma levels in all groups, while NPY remained increased in postprandial period in both patient groups. Ghrelin/obestatin ratio was lower in AN and BN compared to the controls. In conclusions, increased plasma levels of fasting NPY and its unchanged levels after breakfast indicate that NPY is an important marker of eating disorders AN and BN. Different fasting ghrelin and obestatin levels in AN and BN could demonstrate their diverse functions in appetite and eating suppression.
- MeSH
- bulimia nervosa krev MeSH
- dietní sacharidy aplikace a dávkování MeSH
- ghrelin krev MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- mentální anorexie krev MeSH
- neuropeptid Y krev MeSH
- postprandiální období fyziologie MeSH
- přijímání potravy fyziologie MeSH
- složení těla MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dietní sacharidy MeSH
- ghrelin MeSH
- neuropeptid Y MeSH
- obestatin, human MeSH Prohlížeč
OBJECTIVE: The purpose of this study was to examine psychometric properties of the Czech language version of the Adolescent Dissociative Experiences Scale (A-DES) [2]. METHOD: 653 non-clinical participants and 162 adolescent psychiatric inpatients completed Czech versions of the A-DES and the Somatoform Dissociation Questionnaire (SDQ-20), and provided further information (data regarding demographic variables, diagnoses, further psychopathology). RESULTS: The Czech A-DES has very good internal consistency, test-retest reliability and a good validity, though its predictive power is limited. The ADES scores significantly correlate with the measure of somatoform dissociation, a presence of clinician-observed dissociative symptoms, reported traumatic experiences, self injurious behavior, and polysymptomatic diagnostic picture. A-DES scores were significantly higher in ADHD group, but not in a group with a diagnosis of a dissociative disorder. CONCLUSION: The authors stress that all adolescent psychiatric patients who show more complex behavioral disturbances, have histories of trauma, show self-injurious behaviors or have ADHD diagnosis should be screened for dissociation.
- MeSH
- disociační poruchy diagnóza psychologie MeSH
- dítě MeSH
- faktorová analýza statistická MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neparametrická statistika MeSH
- prediktivní hodnota testů MeSH
- průzkumy a dotazníky MeSH
- psychiatrické posuzovací škály * MeSH
- psychometrie MeSH
- reprodukovatelnost výsledků MeSH
- sexuální faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
- Geografické názvy
- Česká republika MeSH
Attention deficit hyperactivity disorder (ADHD) is a common child diagnosis with frequent comorbidities (Quinn, 2008). According to present studies eating disorders may represent one of them (Mikami et al., 2008). Several studies reported ADHD relation to the higher predisposition to obesity (Altafas, 2002), higher values of signs of overnutrition, as body mass index (Waring and Lapane, 2008) or higher value of fat (Ptacek et al., 2009a, c). These characteristics are considered to be directly related to the disorder. They can be caused by impulsivity and probable specific feeding customs of ADHD patients. The presence of eating disorders in ADHD patients could partially explain previously described growth and weight changes.
- MeSH
- dítě MeSH
- hyperkinetická porucha komplikace MeSH
- lidé MeSH
- obezita komplikace MeSH
- poruchy příjmu potravy v dětství komplikace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Visfatin is an adipose tissue-derived hormone shown to correlate with visceral fat mass in patients with obesity. Its possible role in patients with different types of eating disorders is unknown. We measured fasting serum levels of visfatin and leptin and surrogate measures of insulin sensitivity in 10 untreated patients with anorexia nervosa (AN), 10 untreated patients with bulimia nervosa (BN) and 20 age-matched healthy women (C) to study the possible role of visfatin in these disorders. Patients with AN had severely decreased body mass index (BMI) and body fat content. BMI of BN group did not significantly differ from that of C group, whereas body fat content of BN group was significantly lower compared to C and higher compared to AN group, respectively. Serum glucose levels did not significantly differ among the groups studied, whereas serum insulin and leptin levels and HOMA index were significantly decreased in AN group relative to both C and BN group. In contrast, serum visfatin levels in both patients with AN and BN did not differ from those of C group. We conclude that circulating visfatin levels are not affected by the presence of chronic malnutrition in AN or binge/purge eating behavior in BN.
- MeSH
- adipozita MeSH
- biologické markery krev MeSH
- bulimia nervosa krev patofyziologie MeSH
- cytokiny krev MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- inzulin krev MeSH
- krevní glukóza metabolismus MeSH
- leptin krev MeSH
- lidé MeSH
- mentální anorexie krev patofyziologie MeSH
- mladý dospělý MeSH
- nikotinamidfosforibosyltransferasa krev MeSH
- nutriční stav MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- cytokiny MeSH
- inzulin MeSH
- krevní glukóza MeSH
- leptin MeSH
- nicotinamide phosphoribosyltransferase, human MeSH Prohlížeč
- nikotinamidfosforibosyltransferasa MeSH
OBJECTIVE: Anorexia nervosa (AN) is characterized by markedly changes in hormone secretion influencing food intake, energy homeostasis and long-term body weight regulation. The aim of this study was to determine neuropeptide Y (NPY), ghrelin and leptin plasma levels and their changes after six weeks of nutritional-rehabilitation program in severely malnourished anorexia nervosa patients. METHODS: Ten women with DSM-IV diagnosed anorexia nervosa, hospitalized (BMI 14.74 +/- 0.43; age 23.3 +/- 1.0) and ten age-matched healthy women (BMI 21.45 +/- 0.72; age 24.3 +/- 0.8) were enrolled to the study. Fasting plasma levels of NPY, ghrelin and leptin were measured before and after the treatment. RESULTS: Fasting plasma ghrelin and NPY levels were significantly increased in AN patients comparing to healthy women, while plasma leptin was decreased. After six weeks of the treatment plasma ghrelin levels significantly decreased and plasma leptin levels increased. Plasma NPY levels didn't change during the treatment, average BMI significantly increased in AN patients. CONCLUSIONS: We confirmed that ghrelin and leptin plasma levels express actual nutritional status of a body and did change during the six-weeks refeeding in AN patients. Plasma leptin levels together with constantly increased NPY levels indicate to persisting dysregulation of appetite and body weight control mechanisms in AN patients.
- MeSH
- dospělí MeSH
- ghrelin krev MeSH
- leptin krev MeSH
- lidé MeSH
- mentální anorexie krev dietoterapie MeSH
- mladý dospělý MeSH
- neuropeptid Y krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- ghrelin MeSH
- leptin MeSH
- neuropeptid Y MeSH
Serum adipocyte fatty acid-binding protein (FABP) concentrations are linked to human obesity and other features of metabolic syndrome. Whether FABP associates with metabolic alterations in chronic malnutrition is unknown. In the present study, we measured fasting serum levels of FABP, leptin, soluble leptin receptor, adiponectin, resistin, C-reactive protein (CRP), insulin, glucose, cholesterol and triglycerides in 19 patients with a restrictive type of anorexia nervosa (AN) and in 16 healthy age-matched control women (C). Body mass index, serum leptin, and CRP concentrations were significantly lower, while serum adiponectin and soluble leptin receptor levels were significantly higher in AN relative to C group. Serum insulin, glucose, cholesterol and triglyceride levels did not differ between the groups studied. Serum FABP levels were unchanged in patients with AN and were not related to any of parameters studied. We conclude that, in contrast to patients with obesity where FAPB is a prominent marker of metabolic alterations, chronic malnutrition in AN does not significantly affect its serum levels.
- MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- cholesterol krev MeSH
- index tělesné hmotnosti MeSH
- krevní glukóza metabolismus MeSH
- leptin krev MeSH
- leptinové receptory krev MeSH
- lidé MeSH
- mentální anorexie krev metabolismus MeSH
- metabolický syndrom metabolismus MeSH
- metabolismus lipidů MeSH
- mladý dospělý MeSH
- nutriční stav MeSH
- obezita metabolismus MeSH
- proteiny vázající mastné kyseliny krev MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
- cholesterol MeSH
- FABP4 protein, human MeSH Prohlížeč
- krevní glukóza MeSH
- leptin MeSH
- leptinové receptory MeSH
- proteiny vázající mastné kyseliny MeSH
Anorexia nervosa is a serious psychiatric disorder characterized by the inability to maintain normal body weight. The frequently studied polymorphisms in the serotonin 5-HT2A receptor gene (-1438A/G) and in serotonin transporter 5-HTT gene (LPR, VNTR) have led to controversial results in different populations. The aim of the study was to address association of the above-mentioned polymorphisms with anorexia nervosa in the Czech population. We genotyped a well-defined group of 75 patients with anorexia nervosa (average age of 25.39 years, SD 6.18; average BMI 14.65 (SD 1.38)). The control group consisted of 65 Caucasian healthy females (average age 25.76 years, SD 5.12; average BMI 20.69, SD 1.85). The 5-HT2A receptor -1438A/G polymorphism analysis showed a trend for the association with odds ratios for risk allele A being in the same direction. In combination with a previously published Polish cohort, the allelic test reached a suggestive borderline (P = 0.0362, chi2 statistics, 1 df). In meta-analysis which included all published results for allelic tests, the resulting P value was highly significant (0.0003, chi2 statistics, 1 df). Using quantitative association of 5-HTR2A polymorphism with BMI in the Czech sample, a borderline association (P = 0.055) was observed. In 5-HTT, LPR polymorphism analysis, unlike in 5-HT2A, neither allelic nor quantitative association with BMI for the bi-allelic 5-HTT marker was observed. Results of this study support previous reports of a significant role of the A allele (-1438A/G, 5-HT2A receptor) as a risk factor in anorexia nervosa.
- MeSH
- alely MeSH
- dospělí MeSH
- frekvence genu MeSH
- genotyp MeSH
- lidé MeSH
- membránové transportní proteiny pro serotonin genetika MeSH
- mentální anorexie genetika MeSH
- mladý dospělý MeSH
- optimální tělesná hmotnost MeSH
- polymorfismus genetický * MeSH
- receptor serotoninový 5-HT2A genetika MeSH
- serotonin genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- membránové transportní proteiny pro serotonin MeSH
- receptor serotoninový 5-HT2A MeSH
- serotonin MeSH