Shared genetic influences between eating disorders and gastrointestinal disease in a large, population-based sample of adult women and men.

BACKGROUND: Some preliminary research suggests higher rates of gastrointestinal disease in individuals with eating disorders (EDs). However, research is limited, and it remains unknown what etiologic factors account for observed associations. This was the first study to examine how EDs and dimensional ED symptoms (e.g. body dissatisfaction, binge eating) are phenotypically and etiologically associated with gastrointestinal disease in a large, population-based twin sample. METHODS: Adult female (N = 2980) and male (N = 2903) twins from the Michigan State University Twin Registry reported whether they had a lifetime ED (anorexia nervosa, bulimia nervosa, or binge-eating disorder) and completed a measure of dimensional ED symptoms. We coded the presence/absence of lifetime gastrointestinal disease (e.g. inflammatory bowel disease) based on responses to questions regarding chronic illnesses and medications. We first examined whether twins with gastrointestinal disease had higher rates of EDs and ED symptoms, then used correlated factors twin models to investigate genetic and environmental contributions to the overlap between disorders. RESULTS: Twins with gastrointestinal disease had significantly greater dimensional ED symptoms (ß = 0.21, p < 0.001) and odds of a lifetime ED (OR 2.90, p = 0.001), regardless of sex. Shared genetic factors fully accounted for the overlap between disorders, with no significant sex differences in etiologic associations. CONCLUSIONS: Comorbidity between EDs and gastrointestinal disease may be explained by overlap in genetic influences, potentially including inflammatory genes implicated in both types of disorders. Screening for gastrointestinal disease in people with EDs, and EDs in those with gastrointestinal disease, is warranted.

Self-reported food liking and wanting: A factor analytic study of ratings across 49 consecutive days.

Reward responses to food are thought to play an important role in highly palatable food overconsumption. In animal models, food reward responses can be decoupled into unique "liking" (in the moment enjoyment) and "wanting" (motivation/craving) components. However, research on liking and wanting has been hampered by uncertainty regarding whether liking and wanting can be reliably separated in humans. We used factor analysis to test whether ratings of liking and wanting could be empirically separated in women assessed across 49 consecutive days. Female participants (N = 688; ages 15-30) from the Michigan State University Twin Registry reported liking and wanting of foods consumed that day, and wanting of foods not consumed that day, separately for sweets (e.g., cookies), fast food (e.g., French fries), carbohydrates (e.g., bread), and whole foods (fruit, plain chicken) each evening for 49 consecutive days. We examined both average levels and daily levels of liking/wanting across the 49-day period that captured individual differences in liking/wanting over time. Across both types of analyses, liking and wanting for foods that were eaten formed a single factor rather than separate, dissociable factors, while wanting of foods not eaten formed an independent factor. At the daily level, a liking/wanting factor emerged for each individual food category (e.g., liking/wanting sweets), whereas in average analyses, a single factor emerged that collapsed across all food types (i.e., liking/wanting of all foods). Results suggest individuals have difficulty distinguishing between liking and wanting of foods they have eaten on that day but may be able to more reliably separate wanting of foods they have not consumed.

Binge Eating Risk During Midlife and the Menopausal Transition: Sensitivity to Ovarian Hormones as Potential Mechanisms of Risk.

PURPOSE OF REVIEW: Recent research suggests that binge eating may be more prevalent among women in midlife than previously believed. The menopausal transition, an important developmental stage during midlife, is characterized by substantial fluctuations and eventual decreases in ovarian hormones that may contribute to increased risk. This narrative review summarizes findings from studies of binge eating during midlife and menopause and discusses the potential role of ovarian hormones in binge eating risk. RECENT FINDINGS: Studies are few in number and findings are mixed, with only some studies showing increased binge eating during midlife and the menopausal transition. Sensitivity to ovarian hormones, potentially through gene x hormone interactions, may influence who experiences increased binge eating risk and could help explain mixed findings in the field. Future studies of hormone sensitivity and gene x hormone interactions are needed to further elucidate midlife and menopausal risk for binge eating in women.

Associations between household income and disordered eating differ across sex and racial identity in a population-based sample of adults.

BACKGROUND: Most research on socioeconomic status (SES) and eating disorders (EDs) has focused on young White women. Consequently, little is known regarding how SES may relate to EDs/disordered eating in older adults, men, or people with different racial identities. We examined whether associations between SES and EDs/disordered eating differed across age, sex, and racial identity in a large, population-based sample spanning early-to-later adulthood. METHODS: Analyses included 2797 women and 2781 men ages 18-65 (Mage = 37.41, SD = 7.38) from the population-based Michigan State University Twin Registry. We first examined associations between SES and dimensional ED symptoms, binge eating (BE), and self-reported ED diagnoses across age and sex in the full sample. We then examined the impact of racial identity on associations by conducting within- and between-group analyses among Black and White participants. RESULTS: In the full sample, lower SES was associated with significantly greater odds of BE and lifetime EDs in men, but not women, across adulthood. The association between lower SES and greater BE risk was stronger for Black men than for White men, though significant in both groups. Conversely, Black women showed a positive association between SES and dimensional ED symptoms that significantly differed from effects for Black men and White women. CONCLUSIONS: Associations between socioeconomic disadvantage and EDs/disordered eating may be particularly robust for men in adulthood, especially men with a marginalized racial identity. Oppositely, Black women may encounter social pressures and minority stress in higher SES environments that could contribute to somewhat heightened ED risk. PUBLIC SIGNIFICANCE: Little is known regarding how associations between socioeconomic status (SES) and eating disorders (EDs) may differ across age/sex or racial identity. We found lower SES was associated with greater odds of a lifetime ED or binge eating in men only, with a particularly strong association between lower SES and binge eating for Black men. Results highlight the importance of examining how SES-ED associations may differ across other aspects of identity.

A cotwin control study of associations between financial hardship and binge eating phenotypes during COVID-19.

BACKGROUND: COVID-19 was associated with significant financial hardship and increased binge eating (BE). However, it is largely unknown whether financial stressors contributed to BE during the pandemic. We used a longitudinal, cotwin control design that controls for genetic/environmental confounds by comparing twins in the same family to examine whether financial hardship during COVID-19 was associated with BE. METHODS: Female twins (N = 158; Mage  = 22.13) from the Michigan State University Twin Registry rated financial stressors (e.g., inability to afford necessities) daily for 49 consecutive days during COVID-19. We first examined whether financial hardship was associated with BE phenotypes across the full sample. We then examined whether cotwins who differed on financial hardship also differed in BE. RESULTS: Participants who experienced greater mean financial hardship across the study had significantly greater dimensional BE symptoms, and participants who experienced greater financial hardship on a given day reported significantly more emotional eating that day. These results were replicated in cotwin control analyses. Twins who experienced more financial hardship than their cotwin across the study reported greater dimensional BE symptoms than their cotwin, and participants who experienced more financial hardship than their cotwin on a given day reported greater emotional eating that day. Results were identical when restricting analyses to monozygotic twins, suggesting associations were not due to genetic confounds. CONCLUSIONS: Results suggest that BE-related symptoms may be elevated in women who experienced financial hardship during COVID-19 independent of potential genetic/environmental confounds. However, additional research in larger samples is needed. PUBLIC SIGNIFICANCE: Little is known regarding how financial difficulties during the COVID-19 pandemic may have contributed to increased binge eating (BE). We found preliminary evidence that financial hardship during COVID-19 may be associated with greater rates of BE-related symptoms even when comparing twins from the same family. While additional research is needed, results suggest that people who experienced financial hardship during COVID-19 may be at increased risk for BE.

Risk for midlife psychosis in women: critical gaps and opportunities in exploring perimenopause and ovarian hormones as mechanisms of risk.

Women show a heightened risk for psychosis in midlife that is not observed in men. The menopausal transition (i.e. perimenopause) and accompanying changes in ovarian hormones are theorized to account for this midlife increase in risk. This narrative review aims to empirically examine these theories by reviewing studies of midlife and perimenopausal psychosis risk in women and potential ovarian hormone mechanisms of effects. Clinical and pre-clinical studies examining the effects of midlife age, menopausal stage, and ovarian hormones across adulthood on psychosis risk were identified. Synthesis of this body of work revealed that the peak ages of midlife psychosis risk in women overlap with the age range of key menopausal stages (especially the perimenopausal transition), although studies directly assessing menopausal stage are lacking. Studies examining ovarian hormone effects have almost exclusively focused on earlier developmental stages and events (e.g. pregnancy, the menstrual cycle) and show increases in psychotic symptoms in women and female rats during periods of lower estradiol levels. Estrogen treatment also tends to enhance the effects of neuroleptics in females across species at various reproductive phases. Initial data are promising in suggesting a role for menopausal stage and ovarian hormones in psychosis risk. However, critical gaps in our knowledge base remain, as there is a tendency to rely on indirect and proxy measures of menopausal status and hormones. Opportunities for future research are discussed with the goal of increasing research in this critical area of women's health.

Ovarian Hormones and Reward Processes in Palatable Food Intake and Binge Eating.

Ovarian hormones are associated with risk for binge eating in women. Recent animal and human studies suggest that food-related reward processing may be one set of neurobiological factors that contribute to these relationships, but additional studies are needed to confirm and extend findings.

Gonadal Hormone Influences on Sex Differences in Binge Eating Across Development.

PURPOSE OF REVIEW: Binge eating is a transdiagnostic symptom that disproportionately affects females. Sexually dimorphic gonadal hormones (e.g., estradiol, testosterone) substantially impact eating behavior and may contribute to sex differences in binge eating. We examine recent evidence for the role of gonadal hormones in binge eating risk across development. RECENT FINDINGS: Both organizational (long-lasting impact on the central nervous system (CNS)) and activational (transient influences on the CNS) hormone effects may contribute to sex differences in binge eating. Gonadal hormones also impact within-sex variability in binge eating, with higher estradiol levels in females and higher testosterone levels in males protective across development. Emerging evidence suggests that the impact of gonadal hormones may be greatest for people with other risk factors, including genetic, temperamental (e.g., high negative affect), and psychosocial (e.g., exposure to weight-based teasing) risk. Gonadal hormones contribute to sex differences and within-sex variability in binge eating across development.

The effects of puberty on associations between mood/personality factors and disordered eating symptoms in girls.

OBJECTIVE: Negative and positive urgency, anxiety, and depressive symptoms are significant factors of disordered eating (DE) symptoms in early adolescence through young adulthood. However, it is unclear how puberty-a critical developmental milestone that is associated with increased risk for DE symptoms-affects the relationship between these factors and DE symptoms, given that the role of pubertal status has rarely been considered in relation to these associations. Thus, the present study examined whether puberty moderates associations between mood/personality factors and DE in pre-adolescent and adolescent girls. METHOD: Participants included 981 girls (aged 8-16 years) from the Michigan State University Twin Registry. Mood/personality factors, pubertal status, and DE were assessed with self-report questionnaires. RESULTS: Puberty significantly moderated associations between several factors (negative urgency, positive urgency, trait anxiety, depressive symptoms) and the cognitive symptoms of DE (e.g., shape/weight concerns, body dissatisfaction). Associations between mood/personality factors and cognitive DE were stronger in girls with more advanced pubertal status. By contrast, no significant moderation effects were detected for mood/personality-dysregulated eating (e.g., binge eating, emotional eating) associations. DISCUSSION: Findings identify pubertal development as an important moderator of mood/personality-DE symptom associations, especially for cognitive DE symptoms that are known to predict the later onset of clinical pathology.

Low testosterone is associated with dysregulated eating symptoms in young adult men.

OBJECTIVE: Extant animal and human data indicate that natural variation in circulating levels of testosterone may contribute to differential risk for dysregulated eating among males. Indeed, testosterone ablation in postpubertal male rodents results in stimulatory effects on sweet-taste preferences, and lower levels of circulating testosterone in adolescent boys have been found to predict dysregulated eating symptoms during mid-to-late puberty. Nonetheless, no prior study has examined whether lower testosterone is associated with dysregulated eating in adulthood. The current study examined this possibility. METHOD: Participants were 154 young adult men (ages = 18-33) from a large Southwestern University. The Eating Disorder Examination Questionnaire, Eating Pathology Symptoms Inventory, and Loss of Control Over Eating Scale were used to assess three types of dysregulated eating symptoms: eating concerns, binge eating, and loss-of-control eating. Afternoon saliva samples were assayed for testosterone using high-sensitive enzyme immunoassays. RESULTS: Consistent with animal data and prior research in adolescent boys, men with lower testosterone reported significantly higher levels of dysregulated eating symptoms even after controlling for depressive symptoms, body mass index, and age. DISCUSSION: Lower testosterone concentrations might serve as a sex-specific biological factor that contributes to dysregulated eating among men.

The significant effects of puberty on the genetic diathesis of binge eating in girls.

OBJECTIVE: Recent data show significant phenotypic and genetic associations between ovarian hormones and binge eating in adulthood. Theories of hormonal risk focus on puberty and the possibility that hormone activation induces changes in genetic effects that then lead to differential risk for binge eating in postpuberty and adulthood. Although this theory is difficult to test in humans, an indirect test is to examine whether genetic influences on binge eating increase during the pubertal period in girls. Prior work has shown pubertal increases in genetic influences on overall disordered eating symptoms, but no study to date has examined binge eating. The present study was the first to examine these increases for binge eating. METHODS: Participants included 1,568 female twins (aged 8-25 years) from the Michigan State University Twin Registry. Binge eating and pubertal development were assessed with self-report questionnaires. RESULTS: Twin moderation models showed significant linear increases in genetic effects from prepuberty (5%) to postpuberty (42%), even after controlling for the effects of age and body mass index. DISCUSSION: Results provide critical support for increased genetic influences on binge eating during puberty. Additional studies are needed to identify hormonal mechanisms and fully test contemporary models of ovarian hormone risk.

Sex Differences in Binge Eating: Gonadal Hormone Effects Across Development.

Eating disorders are highly sexually differentiated disorders that exhibit a female predominance in risk. Most theories focus on psychosocial explanations to the exclusion of biological/genetic influences. The purpose of this descriptive review is to evaluate evidence from animal and human studies in support of gonadal hormone effects on sex differences in binge eating. Although research is in its nascent stages, findings suggest that increased prenatal testosterone exposure in males appears to protect against binge eating. Although pubertal testosterone may exert additional protective effects, the prenatal period is likely critical for the decreased risk observed in males. By contrast, studies indicate that, in females, it is the lack of prenatal testosterone coupled with the organizational effects of pubertal ovarian hormones that may lead to increased binge eating. Finally, twin data suggest that changes in genetic risk may underlie these hormone influences on sex differences across development.

Facets of Impulsivity and Compulsivity in Women with Anorexia Nervosa.

This study sought to investigate independent associations of impulsivity and compulsivity with eating disorder (ED) symptoms. Women (N = 81) with full or subthreshold Diagnostic and Statistical Manual of Mental Disorders IV anorexia nervosa (AN) completed a semi-structured interview and self-report questionnaires. Multiple regression analyses were conducted using ED symptoms as dependent variables and facets of impulsivity and compulsivity as predictor variables (controlling for body mass index and AN diagnostic subtype). For impulsivity facets, lack of perseverance was uniquely associated with eating concern, shape concern and restraint, whereas negative urgency was uniquely associated with eating concern and frequency of loss of control eating; neither sensation seeking nor lack of premeditation was uniquely associated with any ED variables. Compulsivity was uniquely associated with restraint, eating concern and weight concern. Results support independent associations of impulsivity and compulsivity with ED symptoms in adults with AN, suggesting potential utility in addressing both impulsive and compulsive processes in treatment. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Hormonal Factors and Disturbances in Eating Disorders.

This review summarizes the current state of the literature regarding hormonal correlates of, and etiologic influences on, eating pathology. Several hormones (e.g., ghrelin, CCK, GLP-1, PYY, leptin, oxytocin, cortisol) are disrupted during the ill state of eating disorders and likely contribute to the maintenance of core symptoms (e.g., dietary restriction, binge eating) and/or co-occurring features (e.g., mood symptoms, attentional biases). Some of these hormones (e.g., ghrelin, cortisol) may also be related to eating pathology via links with psychological stress. Despite these effects, the role of hormonal factors in the etiology of eating disorders remains unknown. The strongest evidence for etiologic effects has emerged for ovarian hormones, as changes in ovarian hormones predict changes in phenotypic and genetic influences on disordered eating. Future studies would benefit from utilizing etiologically informative designs (e.g., high risk, behavioral genetic) and continuing to explore factors (e.g., psychological, neural responsivity) that may impact hormonal influences on eating pathology.

Associations between negative affect and binge/purge behaviors in women with anorexia nervosa: Considering the role of negative urgency.

OBJECTIVE: Evidence implicates negative affect in the occurrence of binge/purge behaviors, although the extent to which theoretically relevant individual difference variables may impact this association remains unclear. Negative urgency, the dispositional tendency to engage in rash action when experiencing negative affect, is a unique facet of impulsivity that may play a key role. Moreover, it was hypothesized that women with anorexia nervosa (AN) who are higher on measures of negative urgency, relative to those lower on negative urgency, would exhibit: 1) greater binge eating and purging frequencies on high negative affect days, and 2) a greater change in negative affect prior to and following binge eating and purging episodes. METHOD: Women with AN (n=82) completed a self-report measure of negative urgency and a 2-week ecological momentary assessment protocol in which they recorded binge eating, purging, and negative affect ratings. RESULTS: Women with higher levels of negative urgency exhibited a greater frequency of binge eating and purging; however, in comparison to women low on negative urgency, they: 1) were more likely to binge eat on days corresponding with low-to-moderate negative affect (similar rates of binge eating were observed on high negative affect days), and 2) displayed substantially elevated levels of negative affect across time, and thus, smaller degrees of change in negative affect prior to and following binge eating and purging episodes. DISCUSSION: Negative urgency underlies individual differences in the daily experience of negative affect. Women with AN who are high on negative urgency may have an increased propensity for binge eating and purging via a relatively persistent and heightened state of negative emotions.

Research Review: What we have learned about the causes of eating disorders - a synthesis of sociocultural, psychological, and biological research.

BACKGROUND: Eating disorders are severe psychiatric disorders with a complex etiology involving transactions among sociocultural, psychological, and biological influences. Most research and reviews, however, focus on only one level of analysis. To address this gap, we provide a qualitative review and summary using an integrative biopsychosocial approach. METHODS: We selected variables for which there were available data using integrative methodologies (e.g., twin studies, gene-environment interactions) and/or data at the biological and behavioral level (e.g., neuroimaging). Factors that met these inclusion criteria were idealization of thinness, negative emotionality, perfectionism, negative urgency, inhibitory control, cognitive inflexibility, serotonin, dopamine, ovarian hormones. Literature searches were conducted using PubMed. Variables were classified as risk factors or correlates of eating disorder diagnoses and disordered eating symptoms using Kraemer et al.'s (1997) criteria. FINDINGS: Sociocultural idealization of thinness variables (media exposure, pressures for thinness, thin-ideal internalization, thinness expectancies) and personality traits (negative emotionality, perfectionism, negative urgency) attained 'risk status' for eating disorders and/or disordered eating symptoms. Other factors were identified as correlates of eating pathology or were not classified given limited data. Effect sizes for risk factors and correlates were generally small-to-moderate in magnitude. CONCLUSIONS: Multiple biopsychosocial influences are implicated in eating disorders and/or disordered eating symptoms and several can now be considered established risk factors. Data suggest that psychological and environmental factors interact with and influence the expression of genetic risk to cause eating pathology. Additional studies that examine risk variables across multiple levels of analysis and that consider specific transactional processes amongst variables are needed to further elucidate the intersection of sociocultural, psychological, and biological influences on eating disorders.

An examination of the representativeness assumption for twin studies of eating pathology and internalizing symptoms.

Little research has investigated whether the twin representativeness assumption (that results from twin research generalize to singletons) holds for eating pathology and internalizing symptoms. This study compared disordered eating, depression, and anxiety among young adult female twins versus singletons. Participants included 292 twins and 997 singletons in three samples. Questionnaires included the Minnesota Eating Behavior Survey, Eating Disorder Examination Questionnaire, Beck Depression Inventory, and State-Trait Anxiety Inventory. We examined mean differences between twins' and singletons' scores, after adjusting for age, body mass index, and ethnicity. We found statistically significant mean differences on psychopathology, with twins reporting less disordered eating and internalizing symptoms compared with singletons. Effect sizes of these mean differences were small to moderate. Our results suggest that twins report less disordered eating and internalizing symptoms than singletons, which, combined with the generally small effect sizes, indicate that results from twin samples generalize to singletons.

Ovarian Hormones and Binge Eating in Adulthood: Summary of Findings and Implications for Individual Differences in Risk in Women.

Ovarian hormone influences on general food intake have been studied in animals for 60+ years. Yet, extensions of these data to key eating disorder symptoms in humans (e.g., binge eating (BE)) have only recently occurred. In this article, we summarize findings from studies examining the effects of ovarian hormones on BE. Findings suggest ovarian hormones contribute to BE in animals and humans, although studies are few in number, and effects are not present in all women or all animals exposed to high-risk hormonal milieus. Differences in susceptibility may be due to gene x hormone interactions that can explain why some, but not all, women/females develop BE in the presence of risky hormonal environments.

Estrogen moderation of genetic influences on eating disorder symptoms during gonadarche in girls: Specific effects on binge eating.

The heritability of eating disorder (ED) symptoms increases dramatically across gonadarche in girls. Past studies suggest these developmental differences could be due to pubertal activation of estrogen, but findings have been limited to only one ED symptom (i.e., binge eating). The current study examined whether estrogen contributes to gonadarcheal differences in genetic influences on overall levels of ED symptoms as well as key cognitive symptoms (i.e., weight/shape concerns) that are present across all EDs and are early risk factors for eating pathology. Given that binge eating frequently co-occurs with all of these symptoms, analyses also examined whether estrogen effects exist for overall levels of ED symptoms and body weight/shape concerns after accounting for the known effects of estrogen on genetic risk for binge eating. Participants included 964 female twins (ages 8-16) from the Michigan State University Twin Registry. Overall levels of ED symptoms were assessed with the Minnesota Eating Behavior Survey (MEBS) total score. Weight/shape concerns were assessed with a latent factor modeled using subscales from the MEBS and the Eating Disorder Examination Questionnaire. Estradiol levels were assessed with saliva samples. Twin moderation models were used to examine whether genetic influences on overall levels of ED symptoms and weight/shape concerns differed significantly across estradiol levels. Although initial models suggested modest differences in genetic influences on overall levels of ED symptoms across estradiol levels, these effects were eliminated when binge eating was accounted for in the models. In addition, weight/shape concerns did not show significant moderation of genetic influences by estradiol in models with or without binge eating. Taken together, results are significant in suggesting that individual differences in estradiol levels during gonadarche have a unique and specific impact on genetic risk for binge eating, while other etiologic factors must contribute to increased heritability of cognitive ED symptoms during this key developmental period in girls.

The organizational role of ovarian hormones during puberty on risk for binge-like eating in rats.

Puberty is a high-risk period for the development of dysregulated eating, including binge eating. While risk for binge eating in animals and humans increases in both males and females during puberty, the increased prevalence is significantly greater in females. Emerging data suggest that the organizational effects of gonadal hormones may contribute to the female preponderance of binge eating. In this narrative review, we discuss studies conducted in animals that have examined these organizational effects as well as the neural systems that may serve as intermediary mechanisms. Relatively few studies have been conducted, but data thus far suggest that pubertal estrogens may organize risk for binge eating, potentially by altering key circuits in brain reward pathways. These promising results highlight the need for future studies to directly test organizational effects of pubertal hormones using hormone replacement techniques and circuit-level manipulations that can identify pathways contributing to binge eating across development.