Zugl.: Freiburg (Breisgau), Univ., Diss., 2007

Background: The exonic variant rs6265 in the brain-derived neurotrophic factor (BDNF) has repeatedly been linked to obesity. Objective: To discern the factors by which this effect is conveyed we aimed to investigate its correlation with obesity and metabolic parameters as well as with serum levels of BDNF and measures of energy intake in children. Secondly, we aimed to compare levels of circulating BDNF with metabolic parameters. Methods: We genotyped the variant in 2131 obese and lean children and adolescents (age 6-18 years). In 177 subjects, we determined BDNF serum levels by ELISA and assessed the association with metabolic parameters and data on eating habits from self-reported food diaries. Results: The minor Met-allele was associated with lower body weight (p=0.002). In the entire study cohort none of the investigated metabolic parameters was associated with the variant. When looking at postpubertal subjects, we observed decreased postprandial glucose levels and a decreased HbA1c in Met-allele-carriers after adjusting for BMI (p=0.046 and p=0.012, respectively). Serum BDNF did not differ between homozygous Val/Val-individuals and carriers of the Met-allele. We neither found a correlation of serum BDNF with different genotypes nor with any of the metabolic parameters. Conclusion: We confirmed the association of the minor Met-allele with decreased body weight in children and additionally observed alterations in postprandial glucose metabolism in postpubertal subjects. However, variations in serum levels of BDNF were neither related to the genotype nor to the phenotype of food intake or glucose metabolism.:Inhaltsverzeichnis 2 Abkürzungsverzeichnis 3 1 Einführung in die Thematik 4 1.1 Genetische Ursachen von Adipositas 4 1.2 Der neuronale Wachstumsfaktor BDNF 5 1.3 BDNF und Regulation von Nahrungsaufnahme und Glukosemetabolismus 6 1.4 Der exonisch gelegene Val66Met-Polymorphismus in BDNF 7 1.5 Oraler Glukosetoleranztest und HbA1c als Marker des Glukosestoffwechsels 9 1.5.1 Physiologische Grundlagen der Glukosehomöostase 9 1.5.2 OGTT und Insulinsensitivitätsindizes 10 1.5.3 HbA1c – das „Langzeitgedächtnis“ des Blutzuckerspiegels 10 1.6 Basisdiagnostik des Fettstoffwechsels 11 1.7 Einschätzung der Nährstoffaufnahme mittels Ernährungstagebuch 11 2 Überleitung zur Publikation 13 2.1 Ziel der Arbeit, Rationale und Fragestellung 13 2.2 Charakterisierung der Kohorten 14 2.3 Kurzbeschreibung der Methoden 15 2.4 Ergebnisse 15 2.5 Fazit 16 3 Originalpublikation 17 4 Zusammenfassung 30 5 Literaturverzeichnis 35 6 Anlagen 39 6.1 Erklärung über die eigenständige Abfassung der Arbeit 39 6.2 Spezifizierung des eigenen wissenschaftlichen Beitrages 40 6.3 Danksagung 41

Univ., Diss.--Nürnberg-Erlangen, 2007.

Background. This study sought to determine the distribution of early-onset restrictive eating disturbances characteristic of the new DSM-5 diagnosis, avoidant/restrictive food intake disorder (ARFID) in middle childhood, as well as to evaluate the screening instrument, Eating Disturbances in Youth-Questionnaire (EDY-Q). Methods. A total of 1444 8- to 13-year-old children were screened in regular schools (3rd to 6th grade) in Switzerland using the self-report measure EDY-Q, consisting of 12 items based on the DSM-5 criteria for ARFID. Results. Forty-six children (3.2%) reported features of ARFID in the self-rating. Group differences were found for body mass index, with underweight children reporting features of ARFID more often than normal- and overweight children. The EDY-Q revealed good psychometric properties, including adequate discriminant and convergent validity. Conclusions. Early-onset restrictive eating disturbances are commonly reported in middle childhood. Because of possible negative short- and long-term impact, early detection is essential. Further studies with structured interviews and parent reports are needed to confirm this study’s findings.

The motivational value of food is lower during satiety compared to fasting. Dynamic changes in motivational value promote food seeking or meal cessation. In obesity this mechanism might be compromised since obese subjects ingest energy beyond homeostatic needs. Thus, lower adaptation of eating behaviour with respect to changes in motivational value might cause food overconsumption in obesity. To test this hypothesis, we implemented a selective satiation procedure to investigate the relationship between obesity and the size of the behavioural devaluation effect in humans. Lean to obese men (mean age 25.9, range 19–30 years; mean BMI 29.1, range 19.2–45.1 kg/m2) were trained on a free operant paradigm and learned to associate cues with the possibility to win different food rewards by pressing a button. After the initial training phase, one of the rewards was devalued by consumption. Response rates for and wanting of the different rewards were measured pre and post devaluation. Behavioural sensitivity to reward devaluation, measured as the magnitude of difference between pre and post responses, was regressed against BMI. Results indicate that (1) higher BMI compared to lower BMI in men led to an attenuated behavioural adjustment to reward devaluation, and (2) the decrease in motivational value was associated with the decrease in response rate between pre and post. Change in explicitly reported motivational value, however, was not affected by BMI. Thus, we conclude that high BMI in men is associated with lower behavioural adaptation with respect to changes in motivational value of food, possibly resulting in automatic overeating patterns that are hard to control in daily life.

Objective: Loss of control (LOC) eating is a salient indicator of eating disorder psychopathology in adolescents and is associated with marked distress. While research has focused on the relevance of episode size, clinical significance of LOC eating frequency has rarely been explored. Therefore, this study aimed at identifying LOC eating prevalence with respect to its recurrence and associated variables in a community-based sample. Method: Participants were 1643 adolescents, aged 12-20 years (62.4% female). Based on EDE-Q self-report, participants were categorized as those reporting recurrent (N = 156; 9.5%), non-recurrent (N = 226; 13.8%) and no LOC eating (N = 1261; 76.7%). Results: Adolescents with recurrent LOC eating reported clinically relevant and significantly greater eating disorder psychopathology, functional impairment and distress because of LOC eating, and a significantly higher body mass index (BMI, kg/m2) than adolescents with non-recurrent and those without LOC eating. Discussion: These results underline that LOC eating is a common eating behavior among adolescents in the community associated with clinical characteristics of eating disorders, and could therefore be a risk factor for developing full- or partial-syndrome eating disorders. Further research on the classification of eating disorders in adolescents with LOC eating and severity indicators is warranted.

Objective: This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Method: Using the EDY-Q, a total of 1444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). Results: The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. Discussion: The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews.

‘Der Magen ist die erste Lampe, auf die Öl gegossen werden muss. Sein Sehnen ist genau, sein Trieb so unvermeidlich, dass er nicht einmal lange verdrängt werden kann', schreibt Ernst Bloch, doch seine Aussage greift nicht nur aus psychoanalytischer Sicht zu kurz. Friedrich Nietzsche sieht in 'Essenordnungen' prinzipiell 'Offenbarungen über Kulturen', und natürlich hat Nahrung nicht nur einen körperlich-materiellen, sondern auch einen psychisch-soziokulturellen Aspekt. Nicht ohne Grund besitzen die 'sozialen oder erlernten Aspekte des Ernährungsverhaltens [...] eine größere Zähigkeit oder Konstanz als die biologisch-natürlichen'. Warum sich der Magen 'leichter als der Kopf an neue Speisen' gewöhnt und warum Ernährung keineswegs nur ein 'biochemisches Problem des Stoffwechsels' ist, sondern als ein 'soziales Totalphänomen' aufgefasst werden muss, verdeutlicht D.H. Lawrences Novelle The Virgin and the Gipsy u.a. anhand dessen, was man als ein ebenso elaboriertes wie ambivalentes kulturelles System der Küche bezeichnen kann.

The motivational value of food is lower during satiety compared to fasting. Dynamic changes in motivational value promote food seeking or meal cessation. In obesity this mechanism might be compromised since obese subjects ingest energy beyond homeostatic needs. Thus, lower adaptation of eating behaviour with respect to changes in motivational value might cause food overconsumption in obesity. To test this hypothesis, we implemented a selective satiation procedure to investigate the relationship between obesity and the size of the behavioural devaluation effect in humans. Lean to obese men (mean age 25.9, range 19–30 years; mean BMI 29.1, range 19.2–45.1 kg/m2) were trained on a free operant paradigm and learned to associate cues with the possibility to win different food rewards by pressing a button. After the initial training phase, one of the rewards was devalued by consumption. Response rates for and wanting of the different rewards were measured pre and post devaluation. Behavioural sensitivity to reward devaluation, measured as the magnitude of difference between pre and post responses, was regressed against BMI. Results indicate that (1) higher BMI compared to lower BMI in men led to an attenuated behavioural adjustment to reward devaluation, and (2) the decrease in motivational value was associated with the decrease in response rate between pre and post. Change in explicitly reported motivational value, however, was not affected by BMI. Thus, we conclude that high BMI in men is associated with lower behavioural adaptation with respect to changes in motivational value of food, possibly resulting in automatic overeating patterns that are hard to control in daily life.

Objective: Loss of control (LOC) eating is a salient indicator of eating disorder psychopathology in adolescents and is associated with marked distress. While research has focused on the relevance of episode size, clinical significance of LOC eating frequency has rarely been explored. Therefore, this study aimed at identifying LOC eating prevalence with respect to its recurrence and associated variables in a community-based sample. Method: Participants were 1643 adolescents, aged 12-20 years (62.4% female). Based on EDE-Q self-report, participants were categorized as those reporting recurrent (N = 156; 9.5%), non-recurrent (N = 226; 13.8%) and no LOC eating (N = 1261; 76.7%). Results: Adolescents with recurrent LOC eating reported clinically relevant and significantly greater eating disorder psychopathology, functional impairment and distress because of LOC eating, and a significantly higher body mass index (BMI, kg/m2) than adolescents with non-recurrent and those without LOC eating. Discussion: These results underline that LOC eating is a common eating behavior among adolescents in the community associated with clinical characteristics of eating disorders, and could therefore be a risk factor for developing full- or partial-syndrome eating disorders. Further research on the classification of eating disorders in adolescents with LOC eating and severity indicators is warranted.