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1.  A genome-wide association study of anorexia nervosa 
Boraska, Vesna | Franklin, Christopher S | Floyd, James AB | Thornton, Laura M | Huckins, Laura M | Southam, Lorraine | Rayner, N William | Tachmazidou, Ioanna | Klump, Kelly L | Treasure, Janet | Lewis, Cathryn M | Schmidt, Ulrike | Tozzi, Federica | Kiezebrink, Kirsty | Hebebrand, Johannes | Gorwood, Philip | Adan, Roger AH | Kas, Martien JH | Favaro, Angela | Santonastaso, Paolo | Fernández-Aranda, Fernando | Gratacos, Monica | Rybakowski, Filip | Dmitrzak-Weglarz, Monika | Kaprio, Jaakko | Keski-Rahkonen, Anna | Raevuori, Anu | Van Furth, Eric F | Landt, Margarita CT Slof-Op t | Hudson, James I | Reichborn-Kjennerud, Ted | Knudsen, Gun Peggy S | Monteleone, Palmiero | Kaplan, Allan S | Karwautz, Andreas | Hakonarson, Hakon | Berrettini, Wade H | Guo, Yiran | Li, Dong | Schork, Nicholas J. | Komaki, Gen | Ando, Tetsuya | Inoko, Hidetoshi | Esko, Tõnu | Fischer, Krista | Männik, Katrin | Metspalu, Andres | Baker, Jessica H | Cone, Roger D | Dackor, Jennifer | DeSocio, Janiece E | Hilliard, Christopher E | O'Toole, Julie K | Pantel, Jacques | Szatkiewicz, Jin P | Taico, Chrysecolla | Zerwas, Stephanie | Trace, Sara E | Davis, Oliver SP | Helder, Sietske | Bühren, Katharina | Burghardt, Roland | de Zwaan, Martina | Egberts, Karin | Ehrlich, Stefan | Herpertz-Dahlmann, Beate | Herzog, Wolfgang | Imgart, Hartmut | Scherag, André | Scherag, Susann | Zipfel, Stephan | Boni, Claudette | Ramoz, Nicolas | Versini, Audrey | Brandys, Marek K | Danner, Unna N | de Kovel, Carolien | Hendriks, Judith | Koeleman, Bobby PC | Ophoff, Roel A | Strengman, Eric | van Elburg, Annemarie A | Bruson, Alice | Clementi, Maurizio | Degortes, Daniela | Forzan, Monica | Tenconi, Elena | Docampo, Elisa | Escaramís, Geòrgia | Jiménez-Murcia, Susana | Lissowska, Jolanta | Rajewski, Andrzej | Szeszenia-Dabrowska, Neonila | Slopien, Agnieszka | Hauser, Joanna | Karhunen, Leila | Meulenbelt, Ingrid | Slagboom, P Eline | Tortorella, Alfonso | Maj, Mario | Dedoussis, George | Dikeos, Dimitris | Gonidakis, Fragiskos | Tziouvas, Konstantinos | Tsitsika, Artemis | Papezova, Hana | Slachtova, Lenka | Martaskova, Debora | Kennedy, James L. | Levitan, Robert D. | Yilmaz, Zeynep | Huemer, Julia | Koubek, Doris | Merl, Elisabeth | Wagner, Gudrun | Lichtenstein, Paul | Breen, Gerome | Cohen-Woods, Sarah | Farmer, Anne | McGuffin, Peter | Cichon, Sven | Giegling, Ina | Herms, Stefan | Rujescu, Dan | Schreiber, Stefan | Wichmann, H-Erich | Dina, Christian | Sladek, Rob | Gambaro, Giovanni | Soranzo, Nicole | Julia, Antonio | Marsal, Sara | Rabionet, Raquel | Gaborieau, Valerie | Dick, Danielle M | Palotie, Aarno | Ripatti, Samuli | Widén, Elisabeth | Andreassen, Ole A | Espeseth, Thomas | Lundervold, Astri | Reinvang, Ivar | Steen, Vidar M | Le Hellard, Stephanie | Mattingsdal, Morten | Ntalla, Ioanna | Bencko, Vladimir | Foretova, Lenka | Janout, Vladimir | Navratilova, Marie | Gallinger, Steven | Pinto, Dalila | Scherer, Stephen | Aschauer, Harald | Carlberg, Laura | Schosser, Alexandra | Alfredsson, Lars | Ding, Bo | Klareskog, Lars | Padyukov, Leonid | Finan, Chris | Kalsi, Gursharan | Roberts, Marion | Logan, Darren W | Peltonen, Leena | Ritchie, Graham RS | Barrett, Jeffrey C | Estivill, Xavier | Hinney, Anke | Sullivan, Patrick F | Collier, David A | Zeggini, Eleftheria | Bulik, Cynthia M
Molecular psychiatry  2014;19(10):1085-1094.
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 2,907 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 datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 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 to 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 that 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.
doi:10.1038/mp.2013.187
PMCID: PMC4325090  PMID: 24514567
anorexia nervosa; eating disorders; GWAS; genome-wide association study; body mass index; metabolic
2.  A genome-wide association study of anorexia nervosa 
Boraska, Vesna | Franklin, Christopher S | Floyd, James AB | Thornton, Laura M | Huckins, Laura M | Southam, Lorraine | Rayner, N William | Tachmazidou, Ioanna | Klump, Kelly L | Treasure, Janet | Lewis, Cathryn M | Schmidt, Ulrike | Tozzi, Federica | Kiezebrink, Kirsty | Hebebrand, Johannes | Gorwood, Philip | Adan, Roger AH | Kas, Martien JH | Favaro, Angela | Santonastaso, Paolo | Fernández-Aranda, Fernando | Gratacos, Monica | Rybakowski, Filip | Dmitrzak-Weglarz, Monika | Kaprio, Jaakko | Keski-Rahkonen, Anna | Raevuori, Anu | Van Furth, Eric F | Slof-Op t Landt, Margarita CT | Hudson, James I | Reichborn-Kjennerud, Ted | Knudsen, Gun Peggy S | Monteleone, Palmiero | Kaplan, Allan S | Karwautz, Andreas | Hakonarson, Hakon | Berrettini, Wade H | Guo, Yiran | Li, Dong | Schork, Nicholas J. | Komaki, Gen | Ando, Tetsuya | Inoko, Hidetoshi | Esko, Tõnu | Fischer, Krista | Männik, Katrin | Metspalu, Andres | Baker, Jessica H | Cone, Roger D | Dackor, Jennifer | DeSocio, Janiece E | Hilliard, Christopher E | O’Toole, Julie K | Pantel, Jacques | Szatkiewicz, Jin P | Taico, Chrysecolla | Zerwas, Stephanie | Trace, Sara E | Davis, Oliver SP | Helder, Sietske | Bühren, Katharina | Burghardt, Roland | de Zwaan, Martina | Egberts, Karin | Ehrlich, Stefan | Herpertz-Dahlmann, Beate | Herzog, Wolfgang | Imgart, Hartmut | Scherag, André | Scherag, Susann | Zipfel, Stephan | Boni, Claudette | Ramoz, Nicolas | Versini, Audrey | Brandys, Marek K | Danner, Unna N | de Kovel, Carolien | Hendriks, Judith | Koeleman, Bobby PC | Ophoff, Roel A | Strengman, Eric | van Elburg, Annemarie A | Bruson, Alice | Clementi, Maurizio | Degortes, Daniela | Forzan, Monica | Tenconi, Elena | Docampo, Elisa | Escaramís, Geòrgia | Jiménez-Murcia, Susana | Lissowska, Jolanta | Rajewski, Andrzej | Szeszenia-Dabrowska, Neonila | Slopien, Agnieszka | Hauser, Joanna | Karhunen, Leila | Meulenbelt, Ingrid | Slagboom, P Eline | Tortorella, Alfonso | Maj, Mario | Dedoussis, George | Dikeos, Dimitris | Gonidakis, Fragiskos | Tziouvas, Konstantinos | Tsitsika, Artemis | Papezova, Hana | Slachtova, Lenka | Martaskova, Debora | Kennedy, James L. | Levitan, Robert D. | Yilmaz, Zeynep | Huemer, Julia | Koubek, Doris | Merl, Elisabeth | Wagner, Gudrun | Lichtenstein, Paul | Breen, Gerome | Cohen-Woods, Sarah | Farmer, Anne | McGuffin, Peter | Cichon, Sven | Giegling, Ina | Herms, Stefan | Rujescu, Dan | Schreiber, Stefan | Wichmann, H-Erich | Dina, Christian | Sladek, Rob | Gambaro, Giovanni | Soranzo, Nicole | Julia, Antonio | Marsal, Sara | Rabionet, Raquel | Gaborieau, Valerie | Dick, Danielle M | Palotie, Aarno | Ripatti, Samuli | Widén, Elisabeth | Andreassen, Ole A | Espeseth, Thomas | Lundervold, Astri | Reinvang, Ivar | Steen, Vidar M | Le Hellard, Stephanie | Mattingsdal, Morten | Ntalla, Ioanna | Bencko, Vladimir | Foretova, Lenka | Janout, Vladimir | Navratilova, Marie | Gallinger, Steven | Pinto, Dalila | Scherer, Stephen | Aschauer, Harald | Carlberg, Laura | Schosser, Alexandra | Alfredsson, Lars | Ding, Bo | Klareskog, Lars | Padyukov, Leonid | Finan, Chris | Kalsi, Gursharan | Roberts, Marion | Logan, Darren W | Peltonen, Leena | Ritchie, Graham RS | Barrett, Jeffrey C | Estivill, Xavier | Hinney, Anke | Sullivan, Patrick F | Collier, David A | Zeggini, Eleftheria | Bulik, Cynthia M
Molecular psychiatry  2010;16(9):10.1038/mp.2010.107.
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 2,907 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 datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 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 to 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 that 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.
doi:10.1038/mp.2010.107
PMCID: PMC3859494  PMID: 21079607
anorexia nervosa; eating disorders; GWAS; genome-wide association study; body mass index; metabolic
3.  Primary Amenorrhea in Anorexia Nervosa: Impact on Characteristic Masculine and Feminine Traits 
Animal studies indicate gonadal hormones at puberty have an effect on the development of masculine and feminine traits. However, it is unknown whether similar processes occur in humans. We examined whether women with anorexia nervosa (AN), who often experience primary amenorrhea, exhibit attenuated feminization in their psychological characteristics in adulthood due to the decrease/absence of gonadal hormones at puberty. Women with AN were compared on a number of psychological characteristics using General Linear Models based on the presence/absence of primary amenorrhea. Although women with primary amenorrhea exhibited lower anxiety scores than those without primary amenorrhea, in general, results did not provide evidence of attenuated feminization in women with AN with primary amenorrhea. Future research should utilize novel techniques and direct hormone measurement to explore the effects of pubertal gonadal hormones on masculine and feminine traits.
doi:10.1002/erv.2263
PMCID: PMC4266542  PMID: 24123541
Organizational effects; sex differences; amenorrhea; pubertal timing; anorexia nervosa
4.  Binge Eating, Body Mass Index, and Gastrointestinal Symptoms 
Journal of psychosomatic research  2013;75(5):10.1016/j.jpsychores.2013.08.009.
Objective
Symptoms of both gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) are frequently reported by individuals who binge eat. Higher body mass index (BMI) has also been associated with these disorders and with binge eating (BE). However, it is unknown whether BE influences GERD/IBS and how BMI might affect these associations. Thus, we examined the potential associations among BE, GERD, IBS, and BMI.
Methods
Participants were from the Swedish Twin study of Adults: Genes and Environment (STAGE) and provided information on disordered eating behavior, BMI, gastrointestinal (GI) disorders, and commonly comorbid psychiatric and somatic illnesses. Key features of GERD and IBS were identified to create modified definitions of both disorders that were used as primary outcome variables. Logistic regression models were applied to determine the association between BE and each GERD/IBS both independently and in the context of BMI and other commonly comorbid psychiatric and somatic morbidities.
Results
Prevalence estimates for GERD and IBS were higher among women than men (all p-values < .001). Only the association between BE and IBS was significant in both men and women after adjustment for BMI and the psychiatric/somatic morbidities.
Conclusion
BE appears to be an important consideration in the presence of IBS symptoms in both men and women, even when considering the impact of BMI and other commonly comorbid conditions. This association underscores the importance of routine assessment of BE in patients presenting with IBS to effectively manage the concurrent presentation of these problems.
doi:10.1016/j.jpsychores.2013.08.009
PMCID: PMC3817501  PMID: 24182635
Binge eating; body mass index; gastroesophageal reflux disease; irritable bowel syndrome
5.  Factors Associated With Recovery from Anorexia Nervosa 
Journal of psychiatric research  2013;47(7):972-979.
Previous studies of prognostic factors of anorexia nervosa (AN) course and recovery have followed clinical populations after treatment discharge. This retrospective study examined the association between prognostic factors—eating disorder features, personality traits, and psychiatric comorbidity—and likelihood of recovery in a large sample of women with AN participating in a multi-site genetic study. The study included 680 women with AN. Recovery was defined as the offset of AN symptoms if the participant experienced at least one year without any eating disorder symptoms of low weight, dieting, binge eating, and inappropriate compensatory behaviors. Participants completed a structured interview about eating disorders features, psychiatric comorbidity, and self-report measures of personality. Survival analysis was applied to model time to recovery from AN. Cox regression models were used to fit associations between predictors and the probability of recovery. In the final model, likelihood of recovery was significantly predicted by the following prognostic factors: vomiting, impulsivity, and trait anxiety. Self-induced vomiting and greater trait anxiety were negative prognostic factors and predicted lower likelihood of recovery. Greater impulsivity was a positive prognostic factor and predicted greater likelihood of recovery. There was a significant interaction between impulsivity and time; the association between impulsivity and likelihood of recovery decreased as duration of AN increased. The anxiolytic function of some AN behaviors may impede recovery for individuals with greater trait anxiety.
doi:10.1016/j.jpsychires.2013.02.011
PMCID: PMC3682792  PMID: 23535032
Eating disorders; anorexia nervosa; recovery; prognostic factors; personality; comorbidity
6.  Temporal Sequence of Comorbid Alcohol Use Disorder and Anorexia Nervosa 
Addictive behaviors  2012;38(3):1704-1709.
Women with eating disorders have a significantly higher prevalence of substance use disorders than the general population. The goal of the current study was to assess the temporal pattern of comorbid anorexia nervosa (AN) and alcohol use disorder (AUD) and the impact this ordering has on symptomatology and associated features. Women were placed into one of three groups based on the presence or absence of comorbid AUD and the order of AN and AUD onset in those with both disorders: (1) AN Only, (2) AN First, and (3) AUD First. The groups were compared on psychological symptoms and personality characteristics often associated with AN, AUD, or both using general linear models. Twenty-one percent of women (n = 161) with AN reported a history of AUD with 115 reporting AN onset first and 35 reporting AUD onset first. Women with binge-eating and/or purging type AN were significantly more likely to have AUD. In general, differences were found only between women with AN Only and women with AN and AUD regardless of order of emergence. Women with AN and AUD had higher impulsivity scores and higher prevalence of depression and borderline personality disorder than women with AN Only. Women with AN First scored higher on traits commonly associated with AN, whereas women with comorbid AN and AUD displayed elevations in traits more commonly associated with AUD. Results do not indicate a distinct pattern of symptomatology in comorbid AN and AUD based on the temporal sequence of the disorders.
doi:10.1016/j.addbeh.2012.10.005
PMCID: PMC3558554  PMID: 23254222
anorexia nervosa; alcohol use disorder; comorbidity; age of onset
7.  Initial Reactions to Tobacco Use and Risk of Future Regular Use 
Nicotine & Tobacco Research  2012;15(2):509-517.
Introduction: Studies suggest that initial smoking pleasure influences future smoking behavior. We investigated how initial reactions to cigarettes or Swedish smokeless tobacco (snus) were associated with future use among 10,708 adults from the Swedish Twin Registry.
Methods: The Early Smoking Experience questionnaire captured physiologic reactions to initial tobacco use. Binary recursive partitioning (BRP) identified combinations of initial reactions predictive of regular tobacco use. Analyses, stratified by sex, were conducted separately among those who experimented with only cigarettes (EC), only snus (ES), and both products (EC+S).
Results: Among EC, 39.8% of men and 43.7% of women became smokers, while among ES, 78.6% of men and 53.7% of women became snus users. Among EC+S, 31.3% of men and 20.0% of women became dual users. BRP identified different reactions as predictive of future smoking for men (buzz) and women (dizziness, difficulty inhaling). No initial reaction predicted future snus use among men, but pleasant sensations, later age at first use, and relaxation predicted future snus use for women. Among EC+S, future exclusive use of either product was associated with a favorable initial reaction to that product. Dual users experienced higher prevalence of pleasant reactions and lower prevalence of unpleasant reactions in response to both products.
Conclusions: Our findings support that those who progress to regular tobacco use may be sensitive to the rewarding effects of nicotine but suggest that initial reactions differ by tobacco type. A high proportion of men became regular snus users regardless of initial reactions.
doi:10.1093/ntr/nts180
PMCID: PMC3612000  PMID: 22949572
8.  Pubertal Development Predicts Eating Behaviors in Adolescence 
Objective
Early maturing girls are at increased risk for disordered eating. However, it is unclear if the association between puberty and disordered eating continues throughout pubertal development and if a similar association is exhibited in boys.
Method
Participants included 1340 same- and 624 opposite-sex twins from the Swedish Twin Study of Child and Adolescent Development. Pubertal development was assessed at age 13–14 with the Pubertal Development Scale. General disordered eating, measured with the Eating Disorder Inventory-2 (EDI) was assessed at age 16–17, and dieting and purging behaviors were assessed at both ages 16–17 and 19–20. We applied analysis of variance and logistic regression analyses to determine whether pubertal development in early-to-mid adolescence predicted eating disorder-related behaviors in late adolescence and young adulthood
Results
Pubertal development in early-to-mid adolescence was significantly associated with EDI scores and dieting in late adolescence. No significant association was observed between pubertal development and dieting and purging in young adulthood.
Discussion
Complex combinations of cultural and biological influences likely converge during pubertal development increasing vulnerability to disordered eating. The impact of pubertal development on disordered eating appears to be limited to the adolescent period.
doi:10.1002/eat.22022
PMCID: PMC3404161  PMID: 22522282
disordered eating; eating disorder; puberty; pubertal development; development; adolescence
9.  Shared Genetic Effects Between Age at Menarche and Disordered Eating 
Purpose
An early age at menarche is associated with disordered eating in women. However, it is unclear whether they share genetic factors. The goal of the current study is to delineate the genetic correlation between age at menarche and disordered eating.
Methods
Participants included 427 monozygotic and 329 dizygotic 16-17 year-old female twins from the Swedish Twin Study of Child and Adolescent Development. Disordered eating was assessed with the Eating Disorder Inventory-2. Age at menarche was assessed via self-report. A bivariate correlated factors model was used to delineate the genetic correlation between age at menarche and disordered eating.
Results
The analysis revealed a negative genetic correlation of −.18 in the best-fit model indicating that the genetic factors that influence younger age at menarche are associated with increased liability for disordered eating.
Conclusion
Future research should examine possible causes for this correlation such as the estrogen system and gene-environment interactions.
doi:10.1016/j.jadohealth.2012.02.013
PMCID: PMC3479431  PMID: 23084171
disordered eating; puberty; adolescence; twin study
10.  Dietary Intake in a Randomized-Controlled Pilot of NOURISH: A Parent Intervention for Overweight Children 
Preventive medicine  2012;55(3):224-227.
Objective
NOURISH is a community-based treatment program for parents of overweight and obese children (ages 6–11, BMI ≥ 85th percentile). This study examined the impact of NOURISH on child and parent dietary intake, secondary trial outcomes.
Methods
In Virginia from 2008–2009, this randomized controlled pilot was implemented and dietary assessment of parents and children conducted at baseline, post-test, and 6-month follow-up. Parents (85% female, 62% African American, mean BMI=34.1±9.1) were randomized into intervention (n=46) or control (n=50) groups. Children’s (mean age=8.6±1.5) mean BMI percentile was 98.1±2.6. Parents completed 24-hour dietary records for themselves and their child(ren). Repeated measures analyses assessed treatment effects over time. T-tests evaluated within-group changes from baseline to post-test and to follow-up, using a modified intent-to-treat approach.
Results
Both groups reported significant dietary changes, with few treatment effects found. For parents in NOURISH, significant improvements were found in intakes of total kilocalories/day, grams/day of carbohydrates and sugar, and percent calories from protein (p<0.05). Among control group children, significant improvements in total kilocalories/day and grams/day of carbohydrates and sugar were found (p<0.05).
Conclusions
Among parents who self-select into a childhood obesity program, minimal intervention can elicit short-term dietary changes comparable to those of a structured intervention.
doi:10.1016/j.ypmed.2012.06.016
PMCID: PMC3787076  PMID: 22735041
parent; diet; pediatric obesity
11.  Sleep Problems are Associated with Binge Eating in Women 
Objective
We examined the association among current self-reported sleep problems, lifetime binge eating, and current obesity in women from the Swedish Twin study of Adults: Genes and Environment study
Method
Logistic regression analyses were used to evaluate these associations in 3,790 women aged 20-47 years.
Results
Binge eating was reported by 244 (6.4%) women and was positively associated with not getting enough sleep (p < .015), sleeping poorly (p < .001), problems falling asleep (p < .001), feeling sleepy during work or free time (p < .001), and disturbed sleep (p < .001). These same sleep variables, as well as napping and being a night person, were also significantly associated with obesity. The associations between binge eating and sleep remained after accounting for obesity.
Discussion
This investigation offers empirical support for an independent association between sleep problems and binge eating, which is likely due to complex psychological, biological, neuroendocrine, and metabolic factors.
doi:10.1002/eat.22003
PMCID: PMC3357460  PMID: 22331832
12.  The Significance of Repetitive Hair-Pulling Behaviors in Eating Disorders 
Journal of clinical psychology  2011;67(4):391-403.
We studied the relation between intrusive and repetitive hair-pulling, the defining feature of trichotillomania, and compulsive and impulsive features in 1453 individuals with anorexia nervosa and bulimia nervosa. We conducted a series of regression models examining the relative influence of compulsive features associated with obsessive compulsive disorder; compulsive features associated with eating disorders; trait features related to harm avoidance, perfectionism and novelty seeking; and self harm. A final model with a reduced sample (n=928) examined the additional contribution of impulsive attributes. One out of 20 individuals endorsed hair-pulling. Evidence of a positive association with endorsement of compulsive behavior of the obsessive compulsive spectrum emerged. Hair-pulling may be more consonant with ritualistic compulsions than impulsive urges in those with eating disorders.
doi:10.1002/jclp.20770
PMCID: PMC3664303  PMID: 21365638
eating disorders; trichotillomania; hair-pulling; anorexia nervosa; bulimia nervosa; impulsivity; compulsivity
13.  Effects of Reducing the Frequency and Duration Criteria for Binge Eating on Lifetime Prevalence of Bulimia Nervosa and Binge Eating Disorder: Implications for DSM-5 
Objective
We assessed the impact of reducing the binge eating frequency and duration thresholds on the diagnostic criteria for bulimia nervosa (BN) and binge eating disorder (BED).
Method
We estimated the lifetime population prevalence of BN and BED in 13,295 female twins from the Swedish Twin study of Adults: Genes and Environment employing a range of frequency and duration thresholds. External validation (risk to co-twin) was used to investigate empirical evidence for an optimal binge eating frequency threshold.
Results
The lifetime prevalence estimates of BN and BED increased linearly as the frequency criterion decreased. As the required duration increased, the prevalence of BED decreased slightly. Discontinuity in co-twin risk was observed in BN between at least four times per month and at least five times per month. This model could not be fit for BED.
Discussion
The proposed changes to the DSM-5 binge eating frequency and duration criteria would allow for better detection of binge eating pathology without resulting in a markedly higher lifetime prevalence of BN or BED.
doi:10.1002/eat.20955
PMCID: PMC3235235  PMID: 21882218
14.  Understanding the Association of Impulsivity, Obsessions, and Compulsions with Binge Eating and Purging Behaviors in Anorexia Nervosa 
Objective
To further refine our understanding of impulsivity, obsessions, and compulsions in anorexia nervosa (AN) by isolating which behaviors—binge eating, purging, or both—are associated with these features.
Methods
We conducted regression analyses with binge eating, purging, and the interaction of binge eating with purging as individual predictors of scores for impulsivity, obsessions, and compulsions in two samples of women with AN (n = 1373).
Results
Purging, but not binge eating, was associated with higher scores of impulsivity, obsessions and compulsions. Purging was also associated with worst eating rituals and with worst eating preoccupations.
Conclusion
Our results suggest that purging, compared with binge eating, may be a stronger correlate of impulsivity, obsessions, and compulsions in AN.
doi:10.1002/erv.2161
PMCID: PMC3443865  PMID: 22351620
anorexia nervosa; impulsivity; compulsivity; binge eating; purging
15.  The Heritability of Eating Disorders: Methods and Current Findings 
Family, twin, and adoption studies of anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and the proposed purging disorder presentation (PD) have consistently demonstrated that genetic factors contribute to the variance in liability to eating disorders. In addition, endophenotypes and component phenotypes of eating disorders have been evaluated and provide further insight regarding genetic factors influencing eating disorders and eating disorder diagnostic criteria. Many of these phenotypes have demonstrated substantial heritability. This chapter reviews biometrical genetic methods and current findings from family and twin studies that investigate the role of genes and environment in the etiology of eating disorders. We review the methodology used to estimate heritability, the results of these studies, and discuss the implications of this research for the basic conceptualization of eating disorders and the future value of twin modeling in the molecular genetic era.
doi:10.1007/7854_2010_91
PMCID: PMC3599773  PMID: 21243474
16.  Retrospective Maternal Report of Early Eating Behaviors in Anorexia Nervosa 
European Eating Disorders Review  2011;20(2):111-115.
This exploratory study assessed whether maternal recall of childhood feeding and eating practices differed across anorexia nervosa (AN) subtypes. Participants were 325 women from the Genetics of Anorexia Nervosa study whose mothers completed a childhood feeding and eating questionnaire. Multinomial logistic regression analyses were used to predict AN subtype from measures related to childhood eating: (a) infant feeding (breastfed, feeding schedule, age of solid food introduction), (b) childhood picky eating (picky eating before age one and between ages one and five), and (c) infant gastrointestinal problems (vomiting and colic). Results revealed no significant differences in retrospective maternal report of childhood feeding and eating practices among AN subtypes.
doi:10.1002/erv.1153
PMCID: PMC3391535  PMID: 21830261
Anorexia Nervosa; Anorexia Nervosa Subtype; Feeding; Maternal Report; Infancy
17.  Association between Co-Twin Sex and Eating Disorders in Opposite Sex Twin Pairs: Evaluations in North American, Norwegian, and Swedish Samples 
Objective
These three studies examined the hypothesis that prenatal exposure to sex hormones influences twins’ risk for eating disorders based on co-twin sex, such that individuals with a female co-twin would be more likely than individuals with a male co-twin to meet diagnostic criteria for an eating disorder.
Methods
Male and female twins from the United States (N=2,607), Norway (N=2,796) and Sweden (N=16,458) with known co-twin sex and zygosity were assessed for eating disorders.
Results
In the U.S. and Swedish samples, sex was significantly associated with eating disorder diagnoses, and although co-twin sex was not associated with eating disorders overall, it was associated with broadly defined bulimia nervosa in the Swedish sample. The effects for bulimia were not sustained when monozygotic twins were excluded, suggesting that the effects of prenatal sex hormones play a minor role in influencing eating disorders. Sex and co-twin sex were not associated with eating disorders in the Norwegian sample.
Conclusion
The prenatal sex hormone hypothesis, which proposes that prenatal hormone exposure is associated with later eating disorder symptomatology, was not supported in these three population-based twin samples.
doi:10.1016/j.jpsychores.2011.05.014
PMCID: PMC3246617  PMID: 22200526
eating disorders; estrogen; opposite sex twin pairs; prenatal hormone exposure; testosterone; twin study
18.  Post traumatic stress disorder in anorexia nervosa 
Psychosomatic medicine  2011;73(6):491-497.
Objective
Comorbidity among eating disorders, traumatic events, and post traumatic stress disorder (PTSD) has been reported in several studies. The main objectives of this study were to describe the nature of traumatic events experienced and to explore the relation between PTSD and anorexia nervosa (AN) in a sample of women.
Methods
Eight hundred twenty-four participants from the National Institutes of Health funded Genetics of Anorexia Nervosa Collaborative Study were assessed for eating disorders, PTSD, and personality characteristics.
Results
From a final sample of 753 women with AN, 13.7% (n=103) met DSM-IV criteria for PTSD. The sample mean age was 29.5 years (SD=11.1). In pairwise comparisons across AN subtypes, the odds of having a PTSD diagnosis were significantly lower in individuals with restricting AN (RAN) than individuals with purging AN without binge eating (PAN) (OR=0.49, 95% CI=0.30, 0.80). The majority of participants with PTSD reported the first traumatic event before the onset of AN (64.1%, n=66). The most common traumatic events reported by those with a PTSD diagnosis were sexual related traumas during childhood (40.8%) and during adulthood (35.0%).
Conclusions
AN and PTSD do co-occur and traumatic events tend to occur prior to the onset of AN. Clinically, these results underscore the importance of assessing trauma history and PTSD in individuals with AN and raise the question of whether specific modifications or augmentations to standard treatment for AN should be considered in a subgroup to address PTSD-related psychopathology.
doi:10.1097/PSY.0b013e31822232bb
PMCID: PMC3132652  PMID: 21715295
PTSD; anorexia nervosa; trauma; prevalence; comorbid; epigenetic
19.  Anorexia Nervosa and Generalized Anxiety Disorder: Further Explorations of the Relation Between Anxiety and Body Mass Index 
Journal of anxiety disorders  2011;25(5):727-730.
We explore comorbidity of anorexia nervosa (AN) and generalized anxiety disorder (GAD) and their relation with body mass index (BMI) and evaluate the presence of fasting and excessive exercise which both have anxiolytic and weight loss effects. All participants were female: 32 with AN only, 607 with GAD only, 22 with AN and GAD (AN+GAD), and 5,424 with no history of AN or GAD (referent) from the Swedish Twin study of Adults: Genes and Environment (STAGE). Lowest adult BMI differed significantly (p < .001) and was lower in those with AN+GAD than those with AN only (p < .029). Those with AN+GAD were most likely to endorse fasting and excessive exercise, followed by women with AN only, women with GAD only, and the referent. Comorbid AN and GAD may be a particularly pernicious presentation influencing both BMI and proclivity to engage in behaviors such as fasting and exercise that serve both weight loss and anxiolytic goals.
doi:10.1016/j.janxdis.2011.03.010
PMCID: PMC3094688  PMID: 21514095
Anorexia nervosa; Generalized anxiety disorder; Body mass index; fasting; comorbidity
20.  Impact of Broadening Definitions of Anorexia Nervosa on Sample Characteristics 
Journal of psychiatric research  2010;45(5):691-698.
Practical limitations and sample size considerations often lead to broadening of diagnostic criteria for anorexia nervosa (AN) in research. The current study sought to elucidate the effects of this practice on resultant sample characteristics in terms of eating disorder behaviors, psychiatric comorbidities, temperament and personality characteristics, and heritability point estimates. Three definitions of AN were created: meeting all Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for AN (AN-DSM-IV), meeting all DSM-IV criteria except criterion D, amenorrhea, (AN-noD), and broadening DSM-IV AN criteria by allowing a higher body mass index value, eliminating criterion D, and allowing less stringent body weight concerns (AN-Broad). Using data from the Swedish Twin Registry, 473 women fit one of the three definitions of AN. Women with AN-DSM-IV reported significantly more eating disorder behaviors than women with AN-Broad. Women with AN-noD reported more comorbid psychiatric disorders than women with AN-DSM-IV and AN-Broad. Temperament and personality characteristics did not differ across the three groups. Heritability point estimates decreased as AN definition broadened. Broadening the diagnostic criteria for AN results in an increased number of individuals available for participation in research studies. However, broader criteria for AN yield a more heterogeneous sample with regard to eating disorder symptoms and psychiatric comorbidity than a sample defined by narrower criteria.
doi:10.1016/j.jpsychires.2010.10.003
PMCID: PMC3033482  PMID: 20974478
Anorexia Nervosa; Classification; Diagnostic Criteria; Eating Disorder
21.  Association of Candidate Genes with Phenotypic Traits Relevant to Anorexia Nervosa 
European Eating Disorders Review  2011;19(6):487-493.
This analysis is a follow-up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case-control results revealed no statistically significant differences in single nucleotide polymorphisms, herein we investigate alternative phenotypes associated with AN. In 1762 females using regression analyses we examined: (1) lowest illness-related attained body mass index; (2) age at menarche; (3) drive for thinness; (4) body dissatisfaction; (5) trait anxiety; (6) concern over mistakes; and (7) the anticipatory worry and pessimism vs. uninhibited optimism subscale of the harm avoidance scale. After controlling for multiple comparisons, no statistically significant results emerged. Although results must be viewed in the context of limitations of statistical power, the approach illustrates a means of potentially identifying genetic variants conferring susceptibility to AN because less complex phenotypes associated with AN are more proximal to the genotype and may be influenced by fewer genes.
doi:10.1002/erv.1138
PMCID: PMC3261131  PMID: 21780254
covariates; eating disorders; association studies; personality; genetic
22.  Specific common variants of the obesity-associated FTO gene are not associated with psychological and behavioral eating disorder phenotypes 
Extensive population-based genome-wide association studies have identified an association between the FTO gene and BMI; however, the mechanism of action is still unknown. To determine whether FTO may influence weight regulation through psychological and behavioral factors, seven single nucleotide polymorphisms (SNPs) of the FTO gene were genotyped in 1085 individuals with anorexia nervosa (AN) and 677 healthy weight controls from the international Price Foundation Genetic Studies of Eating Disorders. Each SNP was tested in association with eating disorder phenotypes and measures that have previously been associated with eating behavior pathology: trait anxiety, harm-avoidance, novelty seeking, impulsivity, obsessionality, compulsivity, and concern over mistakes. After appropriate correction for multiple comparisons, no significant associations between individual FTO gene SNPs and eating disorder phenotypes or related eating behavior pathology were identified in cases or controls. Thus, this study found no evidence that FTO gene variants associated with weight regulation in the general population are associated with eating disorder phenotypes in AN participants or matched controls.
doi:10.1002/ajmg.b.31182
PMCID: PMC3249222  PMID: 21438147
23.  Life Beyond the Eating Disorder: Education, Relationships, and Reproduction 
Objective
We investigated sociodemographic characteristics in women with and without lifetime eating disorders.
Method
Participants were from a multi-site international study of eating disorders (N = 2096). Education level, relationship status, and reproductive status were examined across eating disorder subtypes and compared with a healthy control group.
Results
Overall, women with eating disorders were less educated than controls, and duration of illness and age of onset were associated with educational attainment. Menstrual status was associated with both relationship and reproductive status, but eating disorder subtypes did not differ significantly from each other or from healthy controls on these dimensions.
Conclusion
Differences in educational attainment, relationships, and reproduction do exist in individuals with eating disorders and are differentially associated with various eating disorder symptoms and characteristics. These data could assist with educating patients and family members about long-term consequences of eating disorders.
doi:10.1002/eat.20804
PMCID: PMC2888627  PMID: 20143323
Children; relationship; education; anorexia nervosa; bulimia nervosa; amenorrhea
24.  SEXUAL FUNCTIONING IN WOMEN WITH EATING DISORDERS 
Objective
To describe sexual functioning in women with eating disorders.
Method
We assessed physical intimacy, libido, sexual anxiety, partner and sexual relationships in 242 women from the International Price Foundation Genetic Studies relative to normative data.
Results
Intercourse (55.3%), having a partner (52.7%), decreased sexual desire (66.9%), and increased sexual anxiety (59.2%) were common. Women with restricting and purging anorexia nervosa had a higher prevalence of loss of libido than women with bulimia nervosa and eating disorder not otherwise specified (75%, 74.6%, 39% and 45.4%, respectively). Absence of sexual relationships was associated with lower minimum lifetime body mass index (BMI) and earlier age of onset; loss of libido with lower lifetime BMI, higher interoceptive awareness and trait anxiety; and sexual anxiety with lower lifetime BMI, higher harm avoidance and ineffectiveness. Sexual dysfunction in eating disorders was higher than in the normative sample.
Conclusion
Sexual dysfunction is common across eating disorders subtypes. Low BMI is associated with loss of libido, sexual anxiety, and avoidance of sexual relationships.
doi:10.1002/eat.20671
PMCID: PMC2820601  PMID: 19260036
anorexia nervosa; eating disorders; sexual behavior; sexual dysfunction
25.  Childhood Anxiety Associated with Low BMI in Women with Anorexia Nervosa 
Behaviour research and therapy  2009;48(1):60-67.
Objective
Extremely low body mass index (BMI) values are associated with increased risk for death and poor long-term prognosis in individuals with AN. The present study explores childhood personality characteristics that could be associated with the ability to attain an extremely low BMI.
Methods
Participants were 326 women from the Genetics of Anorexia Nervosa (GAN) Study who completed the Structured Interview for Anorexia Nervosa and Bulimic Syndromes and whose mother completed the Child Behavioral Check List and/or Revised Dimensions of Temperament Survey.
Results
Children who were described as having greater fear or anxiety by their mothers attained lower BMIs during AN (p <0.02). Path analysis in the GAN and a validation sample, Price Foundation Anorexia Nervosa Trios Study, confirmed the relation between early childhood anxiety, caloric restriction, qualitative food item restriction, excessive exercise, and low BMI. Path analysis also confirmed a relation between childhood anxiety and caloric restriction, which mediated the relation between childhood anxiety and low BMI in the GAN sample only.
Conclusion
Fearful or anxious behavior as a child was associated with the attainment of low BMI in AN and childhood anxiety was associated with caloric restriction. Measures of anxiety and factors associated with anxiety-proneness in childhood may index children at risk for restrictive behaviors and extremely low BMIs in AN.
doi:10.1016/j.brat.2009.09.009
PMCID: PMC2812624  PMID: 19822312
Anorexia Nervosa; Anxiety; Body Mass Index

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