Molecular Psychiatry (1997) 2, 420–422  1997 Stockton Press All rights reserved 1359–4184/97 $12.00 ORIGINAL RESEARCH ARTICLE Factor Eating Questionnaire1 is considered to be the best tool available for the psychometric assessment of restrained eating.9 Psychometrically defined restrained Restrained eating is eaters consume less energy, take fewer meals and show higher preference for low calorie foods than unre- associated with low leptin strained eaters.10 Restrained eaters have a lower energy levels in underweight expenditure than unrestrained females of comparable lean body mass.11 Ovarial dysfunction occurs more fre- females quently in restrained female eaters.12 Dietary restraint was associated with weight gain in women but not in S von Prittwitz1, WF Blum2,3, A Ziegler4, men in a prospective study of a total of 287 adults fol- S Scharmann1, H Remschmidt1 and lowed-up for one year.13 Both women and those with J Hebebrand1 high dietary restraint are more likely to binge eat.14 In this study we determined serum leptin levels in 1Department of Child and Adolescent Psychiatry; 4Institute 136 underweight and 49 overweight students, who of Medical Biometry, University of Marburg; 2Children’s completed the Three-Factor Eating Questionnaire University Hospital, Gie␤en; 3Lilly GmbH Deutschland, Bad (TFEQ). We hypothesized that individuals with high Homburg, Germany restraint scores have lower serum leptin concentrations than low scoring subjects. Descriptive statistics and Spearman correlations Keywords: anorexia nervosa; eating disorders; body fat between serum log10 leptin levels and BMI, fat mass, mass; diet percent body fat and restraint score, respectively, are Psychometrically defined restrained eaters consume shown in Tables 1 and 2. Log10 leptin levels of only the fewer calories, take fewer meals, show higher prefer- underweight females were negatively correlated with ence for low calorie foods, have lower energy expendi- cognitive restraint scores (r =−0.5; nominal P- ture and a higher rate of ovarial dysfunction than unre- value Ͻ 0.001). strained eaters. We hypothesized that restrained eaters According to the robust linear regression model, per- as assessed with the factor cognitive restraint of the cent body fat and restraint score together account for Three-Factor Eating Questionnaire1 have low leptin lev- 52% of the total variance of log10 leptin levels in the els; therefore, we measured serum leptin levels in 136 underweight female group. BMI and body fat mass had underweight students and 49 overweight students, who no influence; both variables were not included in the had filled out the Three-Factor Eating Questionnaire. model upon use of forward and backward selection. No Body mass indexes, fat mass and percent body fat were interaction effect was significant. Percent body fat and determined. Spearman correlations revealed that log10 leptin levels of only the 67 underweight females were restraint score each account for 41% and 22% (Pseudo- 2 = negatively correlated with cognitive restraint scores Radj 0.22) of the total variance, respectively. (r =−0.5; nominal P-value Ͻ 0.001). The restraint score This is the first study to identify a relationship explained 22% of the total variance of leptin levels in between a score on a psychometric scale and leptin lev- underweight females; in combination with percent body els. The factor cognitive restraint of the TFEQ predicts fat, 52% of the variance was accounted for. To our leptin levels in underweight female students, thus knowledge this is the first study to identify a relation- establishing an important link between the construct ship between a score on a psychometric scale and lep- of restrained eating and leptin levels. Accordingly, tin levels. Restrained eating has a biological correlate in restrained eating has this biological correlate in underweight females. underweight women. We have identified a behavior Leptin is synthesized in fat cells and secreted into that partially accounts for variance of serum leptin 2 the blood stream. Leptin receptors are detectable in levels. 3 several tissues including the hypothalamus where In our study the underweight females constituted the they are involved in the central regulation of body only group with a dependency of leptin levels on the weight homeostasis. Serum leptin levels correlate with restraint score. In this group the restraint score alone body mass index (BMI; kg m−2) and percent body fat.4 accounted for 22% of the total variance of log10 leptin Nevertheless, variance of leptin levels for a given BMI levels; percent body fat and the restraint score together or percent body fat is considerable. Fasting and over- accounted for 52%. Not unexpectedly, such a relation- eating lead to a rapid decrease and increase, respect- ship was not apparent in the male students, who scored ively, of serum leptin levels that precede any weight high on the restraint scale considerably less frequently. alterations.5,6 The reduced synthesis of leptin upon In the 24 overweight females a trend was observed for fasting is involved in the metabolic adaptation to semi- a relationship between the restraint scores and leptin starvation,7 which results in a reduced energy expendi- levels. The low case number needs to be considered. ture. The effect of restrained eating on leptin levels in obese Dietary restraint is a construct which was originally individuals might be obscured by other regulatory based on the observation that individuals with chronic mechanisms. Furthermore, obese individuals with high weight concern are likely to overeat under certain con- restraint scores might not be as successful in restricting ditions.8 The factor cognitive restraint of the Three- their food intake as their underweight counterparts. Restrained eating and low leptin synthesis S von Prittwitz et al 421 Table 1 Body mass indexes, body fat mass, percent body fat, serum log10 leptin levels and scores on the cognitive restraint scale of the Three-Factors Eating Questionnaire in underweight and overweight students

Probands Body mass index Body fat mass Percent body fat Serum log10 leptin Cognitive restraint (kg m−2) range (kg) range range (␮gL−1) score mean ± s.d. mean ± s.d.

Underweight students Females (n = 67) 14.6–19.0 4.4–15.2 11.6–27.7 0.5 ± 0.3 5.0 ± 5.4 Males (n = 69) 17.1–21.8 5.2–13.1 8.1–18.4 −0.3 ± 0.3 2.6 ± 2.1 Overweight students Females (n = 24) 24.7–44.7 22.2–53.2 33.8–49.9 1.3 ± 0.2 7.4 ± 4.6 Males (n = 25) 26.0–36.0 21.2–44.3 26.4–35.0 0.8 ± 0.3 4.4 ± 4.5

Table 2 Spearman correlations between serum log10 leptin levels and body mass index, body fat mass, percent body fat and cognitive restraint score of the Three-Factors Eating Questionnaire, respectively, in underweight and overweight students

Probands log10 leptin to body log10 leptin to body fat log10 leptin to percent log10 leptin to cognitive mass index (kg m−2) mass (kg) body fat restraint score

Underweight students Females (n = 67) 0.19 0.50*** 0.58*** −0.50*** Males (n = 69) 0.41*** 0.46*** 0.31** −0.12 Overweight students Females (n = 24) 0.49* 0.51* 0.59** −0.26 Males (n = 25) 0.64*** 0.78*** 0.87*** −0.21

Uncorrected P-values: *P Ͻ 0.05; **P Ͻ 0.01; ***P Ͻ 0.001.

reduced leptin levels in female restrained eaters under- lie their previously described lower energy expendi- ture11 and their predisposition to ovarial dysfunction.12 Low plasma leptin levels have recently been shown to predict weight gain over a 3-year period in Pima Indi- ans.15 In the light of the fact that restrained eating pre- disposes to weight gain, it appears conceivable that some of these individuals were restrained eaters at baseline. Our findings have considerable implications for eat- ing disorders. Four of the underweight females in this study fulfilled DSM-IV criteria for a current diagnosis of an eating disorder. The two students with anorexia nervosa had cognitive restraint scores of 12 and 18, respectively. A single female fulfilled criteria for Figure 1 Scatterplot and regression line of serum log leptin 10 bulimia nervosa and an additional for an eating dis- levels and the scores of the cognitive restraint factor of the Three-Factor Eating Questionnaire for 67 underweight order not otherwise specified. They scored 13 and 20, female students. respectively. Thus, as expected, patients with eating disorders had high restraint scores reflecting their restrained eating behavior. Patients with anorexia ner- Because low leptin levels might be physiologically rel- vosa have low to very low circulating leptin levels.16 evant for adaptation to semi-starvation,7 leptin levels Females with restrained eating behavior are prone to in overweight individuals might not drop into a critical binge eating14 possibly reflecting an attempt of the range as readily as in underweight subjects. organism to ‘normalize’ its leptin synthesis and in this Leptin levels in restrained eaters are presumably low process to counter-regulate the reduced metabolic because these individuals cognitively restrict their state. energy intake to avoid weight gain. The set points for their individual body weights are presumably higher than their present weights. We speculate that the Restrained eating and low leptin synthesis S von Prittwitz et al 422 Methods leptin in normal human subjects. J Clin Endocrinol Metab 1996; 81: 3419–3423. Volunteer students of the University of Marburg with 6 Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro BMIs below the 15th or above the 85th BMI age-centile JF. Response of leptin to short-term and prolonged overfeeding in 17 humans. J Clin Endocrinol Metab 1996; 81: 4162–4165. were ascertained as described previously. Briefly, 7 Ahima RS, Prabakaran D, Mantzoros C, Qu DQ, Lowell B, Mara- students’ weights and heights were measured. Bio- tosflier E, Flier JS. Role of leptin in the neuroendocrine response electrical impedance measurements (BIA 2000-S; Data to fasting. Nature 1996; 382: 250–252. Input GmbH, Frankfurt) and blood sampling were per- 8 Herman CP, Mack D. Restrained and unrestrained eating. J Person- ality 1975; 43: 647–660. formed after an overnight fast. Percent body fat was 9 Laessle RG, Tuschl RJ, Kotthaus BC, Pirke KM. A comparison of 18 calculated from measured resistance. Students were the validity of three scales for the assessment of dietary restraint. screened for eating disorders using the revised module J Abnorm Psychol 1989; 98: 504–507. for eating disorders of the Composite International 10 Laessle RG, Tuschl RJ, Kotthaus BC, Pirke KM. Behavioral and bio- Diagnostic Interview19 allowing DSM-IV diagnoses. All logical correlates of dietary restraint in normal life. Appetite 1989; 20 12: 83–94. students filled in the German version of the TFEQ. 11 Tuschl RJ, Platte P, Laessle RG, Stichler W, Pirke KM. Energy Serum leptin levels were measured with a radioimmu- expenditure and everyday eating behavior in healthy young noassay.21 women. Am J Clin Nutrition 1990; 52: 81–86. 12 Barr SI, Prior JC, Vigna YM. Restrained eating and ovulatory dis- Spearman correlations between serum log10 leptin turbances: possible implications for bone health. Am J Clin levels and body mass index, body fat mass, percent Nutrition 1994; 59: 92–97. 20 body fat and cognitive restraint score of the TFEQ, 13 Klesges RC, Isbell TR, Klesges LM. Relationship between dietary respectively, were calculated for the four student restraint, energy intake, physical activity, and body weight: a pro- groups. Despite the fact that non-continuity of the spective analysis. J Abnorm Psychol 1992; 101: 668–674. restraint score might apply, we used a robust regression 14 Ruderman AJ. The restraint scale: a theoretical and empirical 22 review. Psychol Bull 1986; 99: 247–262. model for groups, in which a Spearman correlation 15 Ravussin E, Pratley RE, Maffei M, Wang H, Friedman JM, Bennett between serum log10 leptin level and the restraint score PH, Bogardus C. Relatively low plasma leptin concentrations pre- differed significantly (P Ͻ 0.05), in order to assess the cede weight gain in Pima Indians. Nature Med 1997; 3: 238–240. influence of BMI, body fat mass, percent body fat and 16 Hebebrand J, van der Heyden J, Devos R, Ko¨pp W, Herpertz S, restraint score on log leptin levels. Remschmidt H, Herzog W. Plasma concentrations of obese protein 10 in anorexia nervosa. Lancet 1995; 346: 1624–1625. 17 Hinney A, Lentes K-U, Rosenkranz K, Barth N, Roth H, Ziegler A, Hennighausen K, Coners H, Wurmser H, Jacob K, Ro¨mer G, Win- Acknowledgements nikes U, Mayer H, Herzog W, Lehmkuhl G, Schmidt MH, Blum WF, Pirke KM, Scha¨fer H, Grzeschik K-H, Remschmidt H, Hebebrand J. We thank the students for their participation. The ␤3-adrenergic-receptor allele distributions in children, adolescents excellent technical assistance of Ms Hanitsch (Gie␤en) and young adults with obesity, underweight or anorexia nervosa. is gratefully acknowledged. 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N Engl J Med 1996; 334: 292–295. HebebranȰpost.med.uni-marburg.de 5 Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum Received 18 March 1997; revised 13 May 1997; accepted 14 May 1997