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ObjectiveFood insecurity is defined as lack of consistent access to adequate food for healthy living. The objective of this study was to determine the associations between food insecurity and binge-eating disorder in a national cohort of 9- to 14-year-old children.MethodWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,035, 2016-2020). Logistic regression analyses estimated the associations between food insecurity at baseline, year 1, or year 2 (exposure) and binge eating, subclinical binge-eating disorder (Other Specified Feeding and Eating Disorder-Binge-Eating Disorder [OSFED-BED]), and binge-eating disorder (BED) (outcome) based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at 2-year follow-up.ResultsThe prevalence of food insecurity in the study was 15.8%. At 2-year follow-up, 1.71% of the sample received a diagnosis of BED or OSFED-BED, while 6.62% reported binge eating. Food insecurity was associated with 1.67 higher odds of BED or OSFED-BED (95% CI 1.04-2.69) and 1.31 higher odds of binge-eating symptoms (95% CI 1.01-1.71).DiscussionFood insecurity in early adolescence is associated with higher odds of developing future binge-eating and BED or OSFED-BED. Clinicians may consider assessing for binge eating in adolescents with food insecurity and provide support in accessing appropriate food resources.Public significancePrior research has shown that food insecurity is associated with disordered eating behaviors, including binge eating in adulthood. This study explored whether food insecurity in early adolescence increases risk for developing binge-eating disorder (BED). Targeted screening for BED in adolescents experiencing FI, and vice versa, may be warranted.

Suicide is a leading cause of death among adolescents. Emerging literature has described relationships between excessive screen time and suicidal behaviors, though findings have been mixed. The objective of this study is to determine the prospective associations between screen time and suicidal behaviors two-years later in a national (U.S.) cohort of 9-11-year-old-children. We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,633). Logistic regression analyses were estimated to determine the associations between baseline self-reported screen time (exposure) and suicidal behaviors (outcome) based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at two-year-follow-up. Participants reported an average of 4.0 h of total screen time per day at baseline. At two-year-follow-up, 1.38% of the sample reported at least one suicidal behavior. Each additional hour of total screen time was prospectively associated with 1.09 higher odds of suicidal behaviors at 2-year-follow-up (95% CI 1.03-1.14), after adjusting for covariates. For specific screen time modalities, each additional hour of texting (aOR 1.36, 95% CI 1.06-1.74), video chatting (aOR 1.30, 95% CI 1.03-1.65), watching videos (aOR 1.21, 95% CI 1.04-1.39), and playing video games (aOR 1.18, 95% CI 1.01-1.38) was associated with higher odds of subsequent suicidal behaviors. Higher screen time is associated with higher odds of reporting suicidal behaviors at two-year-follow-up. Future research should seek to identify how specific screen time experiences may influence suicidal behaviors.

PurposeThe aim of this study is to determine the prospective associations between baseline screen time and obsessive-compulsive disorder (OCD) at 2-year follow-up in a national (United States) cohort of 9- to 10-year-old children.MethodsWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development study (n = 9,208). Logistic regression analyses were used to determine the associations between baseline self-reported screen time (exposure) and OCD, based on the Kiddie Schedule for Affective Disorders and Schizophrenia (outcome), at 2-year-follow-up, adjusting for race/ethnicity, sex, household income, parent education, family history of psychopathology, and study site, excluding participants with baseline OCD.ResultsThe sample was 48.9% female and racially and ethnically diverse (43.5% non-White). Each additional hour of total screen time was prospectively associated with 1.05 higher odds of OCD at 2-year follow-up (95% confidence interval [CI] 1.01-1.09). For specific screen time modalities, each additional hour of playing video games (adjusted odds ratio 1.15, 95% CI 1.03-1.28) and watching videos (adjusted odds ratio 1.11, 95% CI 1.01-1.23) was associated with a subsequent OCD diagnosis.ConclusionVideo games and watching videos are prospectively associated with new-onset OCD in early adolescents. Future research should examine mechanisms linking these specific screen modalities to OCD development to inform future prevention and intervention efforts.

BackgroundCross-sectional studies have demonstrated associations between screen time and disruptive behavior disorders (conduct disorder and oppositional defiant disorder); however, prospective associations remain unknown. This study's objective was to determine the prospective associations of contemporary screen time modalities with conduct and oppositional defiant disorder in a national cohort of 9-11-year-old children.MethodsWe analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,875). Modified Poisson regression analyses were conducted to estimate the associations between baseline child-reported screen time (total and by modality) and parent-reported conduct or oppositional defiant disorder based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at 1-year follow-up, adjusting for potential confounders.ResultsParticipants reported an average of 4 hr of total screen time per day at baseline. Each hour of total screen time per day was prospectively associated with a 7% higher prevalence of conduct disorder (95% CI 1.03-1.11) and a 5% higher prevalence of oppositional defiant disorder (95% CI 1.03-1.08) at 1-year follow-up. Each hour of social media per day was associated with a 62% higher prevalence of conduct disorder (95% CI 1.39-1.87). Each hour of video chat (prevalence ratio [PR] 1.21, 95% CI 1.06-1.37), texting (PR 1.19, 95% CI 1.07-1.33), television/movies (PR 1.17, 95% CI 1.10-1.25), and video games (PR 1.14, 95% CI 1.07-1.21) per day was associated with a higher prevalence of the oppositional defiant disorder. When examining thresholds, exposure to >4 hr of total screen time per day was associated with a higher prevalence of conduct disorder (69%) and oppositional defiant disorder (46%).ConclusionsHigher screen time was prospectively associated with a higher prevalence of new-onset disruptive behavior disorders. The strongest association was between social media and conduct disorder, indicating that future research and interventions may focus on social media platforms to prevent conduct disorder.

BackgroundRecent research has emphasized a growing trend of weight gain attempts, particularly among adolescents and boys and young men. Little research has investigated these efforts among adults, as well as the specific diet modifications individuals who are trying to gain weight engage in. Therefore, the aims of this study were to characterize the diet modification efforts used by adults across five countries who reported engaging in weight gain attempts and to determine the associations between weight gain attempts and concerted diet modification efforts.MethodsCross-sectional data from the 2018 and 2019 International Food Policy Study, including participants from Australia, Canada, Mexico, the United Kingdom, and the United States (N = 42,108), were analyzed. In reference to the past 12 months, participants reported on weight gain attempts and diet modification efforts related to increased consumption of calories, protein, fiber, fruits and vegetables, whole grains, dairy products, all meats, red meat only, fats, sugar/added sugar, salt/sodium, and processed foods. Unadjusted (chi-square tests) and adjusted (modified Poisson regressions) analyses were conducted to examine associations between weight gain attempts and diet modification efforts.ResultsWeight gain attempts were significantly associated with higher likelihood of each of the 12 forms of diet modification efforts among male participants, and 10 of the diet modification efforts among female participants. Notably, this included higher likelihood of efforts to consume more calories (males: adjusted prevalence ratio [aPR] 3.25, 95% confidence interval [CI] 2.94-3.59; females: aPR 4.05, 95% CI 3.50-4.70) and fats (males: aPR 2.71, 95% CI 2.42-3.03; females: aPR 3.03, 95% CI 2.58-3.55).ConclusionsOverall, the patterns of association between weight gain attempts and diet modification efforts may be indicative of the phenomenon of muscularity-oriented eating behaviors. Findings further highlight the types of foods and nutrients adults from five countries may try to consume in attempts to gain weight.

ObjectiveTo determine the prevalence and sociodemographic correlates of cyberbullying victimization and perpetration among a racially, ethnically and socioeconomically diverse population-based sample of 11-12-year-old early adolescents.MethodsWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2; N = 9429). Multiple logistic regression analyses were used to estimate associations between sociodemographic factors (sex, race/ethnicity, sexual orientation, country of birth, household income, parental education) and adolescent-reported cyberbullying victimization and perpetration.ResultsIn the overall sample, lifetime prevalence of cyberbullying victimization was 9.6%, with 65.8% occurring in the past 12 months, while lifetime prevalence of cyberbullying perpetration was 1.1%, with 59.8% occurring in the past 12 months. Boys reported higher odds of cyberbullying perpetration (AOR 1.71, 95% CI 1.01-2.92) but lower odds of cyberbullying victimization (AOR 0.80, 95% CI 0.68-0.94) than girls. Sexual minorities reported 2.83 higher odds of cyberbullying victimization (95% CI 1.69-4.75) than nonsexual minorities. Lower household income was associated with 1.64 (95% CI 1.34-2.00) higher odds of cyberbullying victimization than higher household income, however household income was not associated with cyberbullying perpetration. Total screen time, particularly on the internet and social media, was associated with both cyberbullying victimization and perpetration.ConclusionsNearly one in 10 early adolescents reported cyberbullying victimization. Pediatricians, parents, teachers, and online platforms can provide education to support victims and prevent perpetration for early adolescents at the highest risk of cyberbullying.

ObjectiveTo determine sociodemographic correlates of problematic screen use (social media, video games, mobile phones) among a racially/ethnically and socioeconomically diverse population-based sample of 10-14-year-old early adolescents.Study designWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020; N = 8753). Multiple linear regression analyses were used to estimate associations between sociodemographic factors (age, sex, race/ethnicity, primary language, household income, parental education) and adolescent-reported problematic video game (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phone use (Mobile Phone Involvement Questionnaire).ResultsBoys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Having unmarried/unpartnered parents was associated with higher problematic social media use. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents (p for interaction

This study examined relationship status (e.g., single versus not single) and number of sexual partners in relation to muscularity- and disordered eating-related attitudes and behaviors among 1090 cisgender gay men enrolled in The PRIDE Study in 2018. Participants completed measures assessing muscle dysmorphia (MD) symptoms, disordered eating attitudes and behaviors, and appearance- and performance-enhancing drug or supplement (APEDS) use. In linear regression models adjusting for theoretically relevant covariates, neither relationship status nor number of past-month sexual partners was associated with disordered eating attitudes. In terms of MD symptoms, single (versus not single) relationship status was associated with greater appearance intolerance, and a greater number of sexual partners was associated with greater drive for size and functional impairment. In adjusted logistic regression models, a greater number of past-month sexual partners was associated with use of anabolic-androgenic steroids, synthetic performance-enhancing substances, protein supplements, and creatine supplements, as well as greater likelihood of engaging in compelled/driven exercise. Across all associations, effect sizes were generally small. Overall, results support that inquiring about sexual partners may have utility in evaluating risk for muscularity-oriented attitudes and behaviors among cisgender gay men. Future work will need to replicate these findings, particularly in more diverse samples.

As current psychosocial and pharmacological interventions show limited efficacy in the treatment of anorexia nervosa (AN), interest in the potential value of neurosurgical intervention and neuromodulation in managing severe and enduring illness has grown. We conducted a systematic review of 20 trials of neurosurgical and neuromodulatory treatments for AN, including neurosurgical ablation, deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, there is evidence to support the role of stereotactic ablation and DBS in the treatment of AN. In contrast, results for rTMS and tDCS have been modest and generally more mixed. Neurosurgical treatment may offer important new avenues for the treatment of AN. Additional randomized clinical trials with comparable patient populations will be needed, in which change in affective, cognitive, and perceptual symptom phenomena, and interrogation of targeted circuits, pre- and post-intervention, are carefully documented.

Sexually dimorphic tissues are formed by cells that are regulated by sex hormones. While a number of systemic hormones and transcription factors are known to regulate proliferation and differentiation of osteoblasts and osteoclasts, the mechanisms that determine sexually dimorphic differences in bone regeneration are unclear. To explore how sex hormones regulate bone regeneration, we compared bone fracture repair between adult male and female mice. We found that skeletal stem cell (SSC) mediated regeneration in female mice is dependent on estrogen signaling but SSCs from male mice do not exhibit similar estrogen responsiveness. Mechanistically, we found that estrogen acts directly on the SSC lineage in mice and humans by up-regulating multiple skeletogenic pathways and is necessary for the stem cell's ability to self- renew and differentiate. Our results also suggest a clinically applicable strategy to accelerate bone healing using localized estrogen hormone therapy.

ObjectiveTo determine sociodemographic correlates of contemporary screen time use among a diverse population-based sample of 9- and 10-year-old children.Study designIn 2021, we analyzed cross-sectional baseline (2016-2018) data from the Adolescent Brain Cognitive Development study (n = 10 755). Multiple linear regression analyses were conducted to estimate associations between sociodemographic factors (sex, race/ethnicity, country of birth, household income, parental education) and 6 contemporary forms of screen time (television, videos [eg, YouTube], video games, social networking, texting, and video chat).ResultsOn average, children reported 3.99 hours of screen time per day across 6 modalities, with the most time spent watching/streaming television shows/movies (1.31 hours), playing video games (1.06 hours), and watching/streaming videos (1.05 hours). On average, Black children reported 1.58 more hours of screen time per day and Asian children reported 0.35 less hours of screen time per day compared with White children (mean 3.46 hours per day), and these trends persisted across most modalities. Boys reported higher overall screen time (0.75 hours more) than girls, which was primarily attributed to video games and videos. Girls reported more time texting, social networking, and video chatting than boys. Higher income was associated with lower screen time usage across all modalities except video chat. However, in high-income households, Latinx children reported 0.65 more hours of screen time per day than White children.ConclusionsGiven the sociodemographic differences in child screen use, guideline implementation strategies can focus on key populations, encourage targeted counseling by pediatricians, and adapt Family Media Use Plans for diverse backgrounds.

ObjectiveThere is a paucity of prospective research exploring the relationship among contemporary screen time modalities (e.g., video streaming, video chatting, texting and social networking) and body mass index (BMI) percentile. The objective of this study was to determine the prospective associations between screen time behaviours in a large and demographically diverse population-based cohort of 9-10-year-old children and BMI percentile at 1-year follow-up.MethodsWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11 066). Multiple linear regression analyses were conducted to estimate associations between baseline screen time behaviours (exposure) and BMI percentile at 1-year follow-up, adjusting for race/ethnicity, sex, household income, parent education, depression, binge-eating disorder and baseline BMI percentile.ResultsEach additional hour of total screen time per day was prospectively associated with a 0.22 higher BMI percentile at 1-year follow-up (95% CI 0.10-0.34) after adjusting for covariates. When examining specific screen time behaviours, each additional hour of texting (B = 0.92, 95% CI 0.29-1.55), video chat (B = 0.72, 95% CI 0.09-1.36) and video games (B = 0.42, 95% CI 0.06-0.78) was significantly prospectively associated with higher BMI percentile.ConclusionsScreen time is prospectively associated with a higher BMI percentile 1 year later among children 9-10 years old.

BackgroundRepresenting the pathological extreme pursuit of muscularity, muscle dysmorphia (MD) is characterized by a pervasive belief or fear around insufficient muscularity and an elevated drive for muscularity. Despite evidence of elevated body image-related concerns among sexual minority populations, little is known about the degree of muscle dysmorphia (MD) symptoms among sexual minorities, particularly based on Muscle Dysmorphic Disorder Inventory (MDDI) scores. The objective of this study was to examine the nature and severity of MD symptoms in cisgender sexual minority men and women and provide community norms of the MDDI for these populations.MethodsData from participants in The PRIDE Study, an existing study of health outcomes in sexual and gender minority people from the United States, were examined. Participants included cisgender gay men (N = 1090), cisgender bisexual plus (bisexual, pansexual, and/or polysexual) men (N = 100), cisgender lesbian women (N = 563), and cisgender bisexual plus women (N = 507). We calculated means, standard deviations (SD), and percentiles for the MDDI total and subscale scores for cisgender sexual minority men and women. We compared MDDI scores by sexual orientation using linear regression models, both unadjusted and adjusted for sociodemographics.ResultsOverall, the sample was 85.2% White, 3.0% Asian or Pacific Islander, 2.0% Black, 0.5% Native American, 3.9% multiracial, and 6.6% Hispanic/Latino/a. The mean age was 38.6 (SD = 14.3) and 69.4% had a college degree or higher. Means (SD) for the MDDI total score were 27.4 (7.7) for cisgender gay men, 26.4 (6.4) for cisgender bisexual plus men, 24.3 (6.1) for cisgender lesbian women, and 24.6 (5.5) for cisgender bisexual plus women. There were no significant differences in MDDI scores between cisgender gay and bisexual plus men, or between cisgender lesbian women and bisexual plus women in unadjusted or adjusted models.ConclusionsThese normative data provide insights into the experience of MD symptoms among cisgender sexual minority men and women and can aid researchers and clinicians in the evaluation of MD symptoms and interpretation of MDDI scores in sexual minority populations.

Despite increasing empirical interest in muscle dysmorphia (MD), a dearth of research has assessed this construct in sexual minority populations. In particular, the psychometric properties of one of the most widely used measures of MD symptoms-the Muscle Dysmorphic Disorder Inventory (MDDI)-have not been evaluated in sexual minority populations despite emerging evidence suggesting differential risk for MD symptoms across sexual orientation groups. In this study, we assessed the psychometric properties of the MDDI in a sample of 715 cisgender gay men and 404 cisgender lesbian women ages 18-50 years who participated in a large-scale national longitudinal cohort study of sexual and gender minority adults. The factor structure of the MDDI was examined in each sample using a two-step, split-sample exploratory and confirmatory factor analytic approach. Exploratory factor analysis supported a three-factor structure in both samples, which were confirmed by confirmatory factor analysis. Moreover, results supported the internal consistency reliability and convergent validity of the MDDI subscales in both samples. Cumulatively, these findings suggest that the MDDI is an appropriate measure of MD symptoms among cisgender gay men and cisgender lesbian women.

ObjectiveTo determine the prospective associations between contemporary screen time modalities in a nationally representative cohort of 9-10-year-old children and binge-eating disorder at one-year follow-up.MethodWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,025). Logistic regression analyses were conducted to estimate associations between baseline child-reported screen time (exposure) and parent-reported binge-eating disorder based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5, outcome) at one-year follow-up, adjusting for race/ethnicity, sex, household income, parent education, BMI percentile, site, and baseline binge-eating disorder.ResultsEach additional hour of total screen time per day was prospectively associated with 1.11 higher odds of binge-eating disorder at 1-year follow-up (95% CI 1.05-1.18) after adjusting for covariates. In particular, each additional hour of social networking (aOR 1.62, 95% CI 1.18-2.22), texting (aOR 1.40, 95% CI 1.08-1.82), and watching/streaming television shows/movies (aOR 1.39, 95% CI 1.14-1.69) was significantly associated with binge-eating disorder.DiscussionClinicians should assess screen time usage and binge eating in children and adolescents and advise parents about the potential risks associated with excessive screen time.

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships.

ObjectiveAnorexia nervosa (AN) is a disorder characterized by a profound fear of weight gain, resulting in significant weight loss, as well as behavioral symptoms that interfere with weight normalization. In concert, weight gain remains a proximal goal of treatment, and patient weighing is a critical component of treatment. However, divergent approaches exist in how patient weighing is undertaken in clinical practice. The aim of this study is to investigate the impact of a brief course of open weighing (sharing weight data with patients) versus blind weighing (not sharing weight data with patients) on distress around being weighed and AN symptom severity.Method216 patients with AN and atypical AN will be randomized to receive 4 weeks of open or blind weighing practices across residential, intensive outpatient, and outpatient treatment settings, within the context of manualized empirically supported treatment. Following 4 weeks of open or blind weighing, all patients will be enrolled into open weighing practices. Primary outcomes of interest will be patient-reported distress around being weighed at week 5 and eating disorder symptom severity at week 5. Secondary outcomes will assess weight prediction error, intolerance of uncertainty, and the fear of food.DiscussionNo best practice guidelines exist in determining optimal practices around weighing patients with AN. This multisite randomized controlled trial will provide the first known data on the impact of open versus blind weighing practices upon weight-related distress and AN symptom severity.

Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5-7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.

ObjectivePrevious research supports the relevance of early symptom change in eating disorder (ED) treatment; however, few studies have distinguished early weight change from early change in ED psychopathology, particularly in higher levels of care. Thus, the present study examined whether early change in weight and ED psychopathology predicted outcome for adolescents with anorexia nervosa (AN) in a partial hospitalization program.MethodAdolescents with AN (n = 99) completed assessments at admission, 1-month after treatment admission, discharge, and 6-month follow-up.ResultsHigher admission percent expected body weight (%EBW), greater early change in %EBW, longer duration of treatment, shorter length of illness, and earlier age of onset predicted greater change in %EBW at discharge, but not follow-up. Greater ED psychopathology at admission and greater early change in ED psychopathology predicted later change in ED symptoms at discharge, but not follow-up. Neither early change in %EBW nor ED psychopathology predicted likelihood of remission at discharge and follow-up.DiscussionResults support the importance of early change in predicting later change in the same ED outcome variables and suggest that early change in both %EBW and ED psychopathology in adolescents may be an important area for future research.

ObjectiveTo determine adolescent predictors of muscularity-oriented disordered eating behaviors in young men and women using a nationally representative longitudinal sample in the United States and to examine differences by sex.MethodWe used nationally representative longitudinal cohort data collected from baseline (11-18 years old, 1994-1995) and 7-year follow-up (18-24 years old, 2001-2002) of the National Longitudinal Study of Adolescent to Adult Health. We examined adolescent demographic, behavioral, and mental health predictors of young adult muscularity-oriented disordered eating behaviors defined as eating more or differently to gain weight or bulk up, supplements to gain weight or bulk up, or androgenic anabolic steroid use at 7-year follow-up.ResultsOf the 14,891 included participants, 22% of males and 5% of females reported any muscularity-oriented disordered eating behavior at follow-up in young adulthood. Factors recorded at adolescence that were prospectively associated with higher odds of muscularity-oriented disordered eating in both sexes included black race, exercising to gain weight, self-perception of being underweight, and lower body mass index z-score. In addition, participation in weightlifting; roller-blading, roller-skating, skate-boarding, or bicycling; and alcohol among males and depressive symptoms among females during adolescence were associated with higher odds of muscularity-oriented disordered eating in young adulthood.ConclusionsInterventions to prevent muscularity-oriented disordered eating behaviors may target at-risk youth, particularly those of black race or who engage in exercise to gain weight. Future research should examine longitudinal health outcomes associated with muscularity-oriented disordered eating behaviors.

ObjectiveThe evolution toward more stringent conceptualizations of remission in family therapy for adolescent anorexia nervosa (AN) has, with time, introduced variability in outcomes across randomized controlled trials (RCTs). An examination of remission across the history of research on family therapy for AN shows that earlier studies adopted lenient definitions and generally yielded higher rates of remission than studies of the past decade that have used stricter definitions of remission. In this study, we investigate the reactivity of remission rates to the application of different definitions of remission used within the family therapy for AN literature, within a single RCT data set.MethodWe conducted a secondary analysis of data from a single-site RCT which compared the relative efficacy of two formats of family therapy in a sample of 106 Australian adolescents with AN. Using end-of-treatment data, we compared remission rates using 11 definitions of remission that have been used in studies of family therapy for AN spanning more than three decades.ResultsWe found wide variability in remission rates (21.7-87.7%; Cochran's Q χ2 (10, N = 106) = 303.55, p = .000], depending on which definition of remission was applied. As expected, more lenient criteria produced higher remission rates than more stringent definitions.DiscussionApplying different criteria of remission to a single data set illustrates the impact of changing how remission is defined. Failure to consider the greater stringency of remission criteria in recent studies could result in false inferences concerning the efficacy of family therapy for AN over time.

BackgroundThe relationship between genetic risk for body mass index (BMI) and weight control behaviors remains unknown. The objectives of this study were to determine the association between genetic risk for BMI and weight control behaviors in young adults, and to examine actual measured BMI as a potential mediator variable.MethodWe analyzed data from three data collection waves of the National Longitudinal Study of Adolescent to Adult Health. The BMI polygenic score (PGS) was based on published genome-wide association studies for BMI. BMI was collected at 11-18 years and 18-26 years. Weight control behaviors included self-reported: (a) weight loss behaviors (dieting, vomiting, fasting/skipping meals, diet pills, laxatives, or diuretic use to lose weight) and (b) weight gain behaviors (eating more or different foods than normal, taking supplements to gain weight).ResultsAmong 4,397 participants, the BMI PGS was associated with higher odds of weight loss behaviors in females (OR 1.24, 95% CI 1.14-1.35) and males (OR 1.43, 95% CI 1.26-1.62), and this association was mediated by BMI (indirect effect 0.04, 95% CI 0.03-0.05 in females and 0.03, 95% CI 0.03-0.04 in males). The BMI PGS was associated with lower odds of weight gain behaviors in females and males, which was also mediated by actual BMI.ConclusionsThe BMI PGS was associated with weight loss behaviors in both males and females, and this association was mediated by actual measured BMI. Clinical interventions to prevent high BMI, particularly for individuals with genetic risk, may also prevent subsequent development of potentially unhealthy weight loss behaviors.

ObjectiveTo determine the prevalence of weight-gain attempts in adolescent boys in the United States.MethodsParticipants were 15,624 high school students from the nationally representative 2015 Youth Risk Behavior Survey.ResultsOverall, 29.6% of adolescent boys reported attempts to gain weight, including 39.6% of boys who were normal weight, 12.8% who were overweight, and 10.6% who were obese by body mass index (BMI). In contrast, only 6.5% of adolescent girls reported attempts to gain weight. Although only 3.3% of adolescent males are underweight by BMI, 19.3% perceive themselves to be underweight. Further, over half of adolescent males who are overweight by BMI perceive themselves to be about the right weight. Black/African-American (odds ratio [OR] 1.89; 95% confidence interval [CI] 1.50-2.38) and multiracial (OR 1.62; 95% CI 1.16-2.26) adolescent males had greater odds of weight-gain attempts than white adolescent males. Adolescent males identifying as bisexual had lower odds (OR .47; 95% CI .25-.88) of weight-gain attempts than adolescent males identifying as heterosexual.ConclusionsWeight-gain attempts are common among adolescent boys including those who are considered normal weight, overweight, or obese by BMI; African-American or multiracial; and those self-identifying as heterosexual. Consideration of the unique nature of male body image, particularly adolescent boys' perceptions of their own weight and weight-gain attempts, should be incorporated into primary care screening for adolescent boys.

Recent research has identified the important but overlooked role of negative affect in the maintenance of dietary restriction. However, understanding how fluctuations in negative affect relate to symptoms of anorexia nervosa (AN) during treatment is limited. In a longitudinal study, the reciprocal associations between higher and lower order dimensions of negative affect and dietary restraint were examined in adolescents undergoing treatment for AN. The sample consisted of 107 adolescents (Mage = 15.5, SD = 1.5 years) who underwent family-based treatment over the course of 6 months. Self-report data assessing negative affect and dietary restraint were collected at baseline, 6 times throughout treatment, and again at the end of treatment. Findings from lagged hierarchical linear models revealed reciprocal associations between higher order negative affect and dietary restraint but unidirectional associations among some dimensions of lower order affect. Specifically, dietary restraint predicted increased guilt and hostility, whereas fear predicted increased dietary restraint. These findings highlight the importance of examining the distinct dimensions of negative emotion and the temporal role of fear in precipitating dietary restraint, and guilt and hostility in proceeding dietary restraint. Collectively, these findings emphasize the functional nature of different emotions in the process of AN remission and provide preliminary evidence of affective mechanisms related to change in symptomatology during treatment for adolescent AN. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PurposeTo determine if previously reported risk factors for the development of unhealthy weight control behaviors differ by sex and weight status using a nationally representative longitudinal sample of adolescents followed through young adulthood.MethodsWe used nationally representative longitudinal cohort data collected from baseline (11-18 years old, 1994-1995, Wave I) and seven-year follow-up (18-24 years old, 2001-2002, Wave III) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). We examined potential risk factors (adverse childhood events and adolescent family, school, body image, and mental health factors) for the development of unhealthy weight control behaviors including vomiting, fasting/skipping meals, or laxative/diuretic use to lose weight at seven-year follow-up in young adulthood.ResultsOf the 14,322 included subjects, 11% reported unhealthy weight control behavior at follow-up in young adulthood, with the highest proportion (23.7%) among overweight/obese females and the lowest proportion (3.7%) among underweight/normal weight males. All adolescent family factors were significantly associated with unhealthy weight control behaviors in underweight/normal weight females, whereas none were significantly associated in overweight/obese males. Similar trends were noted for adverse childhood events, and adolescent school and community factors. Adolescent self-perception of being overweight was associated with young adult unhealthy weight control behaviors among all subgroups.ConclusionsRisk factors for unhealthy weight control behaviors may differ based on sex and weight status. Screening, prevention, and treatment interventions for unhealthy weight control behaviors in adolescents and young adults may need to be tailored based on sex and weight status.

BackgroundClinical and community samples indicate that eating disorders (EDs) and disordered eating behaviors (DEBs) may co-occur among adolescents and young adults at a weight status classified as overweight or obese.ObjectiveTo determine the prevalence of EDs and DEBs among young adults at a weight status classified as overweight or obese using a nationally representative sample and to characterize differences in prevalence by sex, race/ethnicity, sexual orientation, and socioeconomic status.DesignCross-sectional nationally representative data collected from Wave III of the National Longitudinal Study of Adolescent to Adult Health (Add Health).ParticipantsYoung adults ages 18-24 years old.Main measuresED diagnosis and DEBs (self-reported binge eating or unhealthy weight control behaviors including vomiting, fasting/skipping meals, or laxative/diuretic use to lose weight). Covariates: age, sex, race/ethnicity, sexual orientation, weight status, and education.Key resultsOf the 14,322 young adults in the sample, 48.6% were at a weight status classified as overweight or obese. Compared to young adults at a weight status classified as underweight or normal weight, those at a weight status classified as overweight or obese reported a higher rate of DEBs (29.3 vs 15.8% in females, 15.4 vs 7.5% in males). Logistic regression analyses demonstrated that odds of engaging in DEBs were 2.32 (95% confidence interval 2.05-2.61) times higher for females compared to males; 1.66 (1.23-2.24) times higher for Asian/Pacific Islander compared to White; 1.62 (1.16-2.26) times higher for homosexual or bisexual compared to heterosexual; 1.26 (1.09-1.44) times higher for high school or less versus more than high school education; and 2.45 (2.16-2.79) times higher for obesity compared to normal weight, adjusting for all covariates.ConclusionsThe high prevalence of DEBs particularly in young adults at a weight status classified as overweight or obese underscores the need for screening, referrals, and tailored interventions for DEBs in this population.

ObjectiveTo determine if unhealthy weight control behaviors or binge-eating behaviors among young adults with overweight/obesity are associated with body mass index (BMI) change and cardiometabolic risk at 7-year follow-up.MethodsWe used longitudinal cohort data from 5,552 young adults with overweight/obesity at baseline (18-24 years) with 7-year follow-up (24-32 years) from the National Longitudinal Study of Adolescent to Adult Health. Baseline predictors were: (a) unhealthy weight control behaviors such as vomiting, fasting, skipping meals, or laxative/diuretic use to lose weight; or (b) binge-eating behaviors. Participants reporting either unhealthy weight control behaviors or binge-eating behaviors were considered to engage in any disordered eating behavior (DEB). Outcomes at 7-year follow-up were BMI change, incident diabetes, incident hypertension, and incident hyperlipidemia.ResultsYoung adults with overweight/obesity reporting unhealthy weight control behaviors at baseline had higher BMI and weight at 7-year follow-up than those without unhealthy weight control behaviors. In regression models adjusting for baseline BMI, race/ethnicity, age, and education, unhealthy weight control behaviors were associated with greater change in BMI in both sexes and binge-eating behavior at baseline was associated with greater odds of incident hyperlipidemia (odds ratio 1.90, 95% CI 1.29-2.79) at 7-year follow-up in males.ConclusionsThe higher risk for increased BMI (in both males and females) and incident hyperlipidemia (in males) over time in young adults with overweight/obesity who engage in DEBs underscores the need to screen for DEBs in this population and provide referrals and tailored interventions as appropriate.

ObjectiveThis study aimed to examine the trajectory of symptom remission and affective functioning throughout the course of two family-based treatments for adolescent anorexia nervosa (AN): conjoint family-based treatment (FBT) and parent-focused treatment (PFT).MethodParticipants were 107 adolescents (Mage  = 15.5 years, SD = 1.5) with a primary diagnosis of AN who participated in a randomized clinical trial comparing FBT (N = 55) and PFT (N = 51). Patient weight and self-reported assessments of dietary restraint and positive and negative affect were recorded at regular intervals throughout treatment.ResultsMultilevel models revealed increases in weight (β = 0.33, p

By virtue of adopting the core symptomatic fear (i.e., a fear of weight gain) as a primary treatment target, the treatment of AN centrally involves exposure-driven processes. However, exposure trials targeting the fear of weight gain in AN have been sparse, yielding mixed results to date. In translating extinction theory to the treatment of AN, it is likely that the absence of a clear distinction between what constitutes the core feared cue and the core feared outcome has stymied the application of exposure treatments in AN. This review considers several configurations of the core fear association in AN, noting distinct therapeutic strategies which may allow for more precise efforts in violating fear-based expectancies. Specific guidance is offered in the clinical decision making process as to which strategies might best promote inhibitory learning, and a clinical case is discussed, in which treatment was adjusted to specifically violate the core underlying fear association.

ObjectiveThe objective of this study was to review the current eating disorders outcome literature after residential or partial hospitalization programme (PHP) treatment.MethodArticles were identified through a systematic search of PubMed and PsycINFO.ResultsTwenty-two PHP and six residential treatment studies reported response at discharge and tended to find improvement. Fewer studies (nine PHP and three residential) reported outcome at some interval after discharge from treatment. These tended to find sustained improvement. A substantial proportion of patients were lost to follow-up, particularly for residential treatment. Only two follow-up studies used controlled trials; both showed efficacy for PHP compared with inpatient treatment with regard to maintaining symptom remission.ConclusionsImprovement at discharge may not predict long-term outcome. Long-term follow-up studies were confounded by high dropout rates. While higher levels of care may be essential for reversing malnutrition, there remains a lack of controlled trials showing long-term efficacy, particularly for residential treatment settings. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Adolescent bulimia nervosa (BN) remains relatively understudied, and the complex interaction between core eating psychopathology and emotional regulation difficulties provides ongoing challenges for full symptom remission. In an open pilot trial, we aimed to investigate the efficacy of a program integrating family-based treatment (FBT) and dialectical behavior therapy (DBT) in treating adolescent BN, without exclusion criteria. Participants were 35 adolescents who underwent partial hospital treatment for BN, and outcomes included measures of core BN pathology and emotional regulation difficulties, as well as parental measures of self-efficacy, completed at intake and discharge. Results indicate significant improvements in overall eating disorder pathology, t(68) = 4.52, p = .002, and in core BN symptoms, including objective binge episodes, t(68) = 2.01, p = .041, and self-induced vomiting, t(68) = 2.90, p = .005. Results also illustrated a significant increase in parental efficacy throughout the course of treatment, t(20) = .081, p = .001, although no global improvement in difficulties in emotion regulation was noted, t(68) = 1.12, p = .285. These preliminary findings support the utility of this integration of FBT and DBT, although raise interesting questions as to the mechanism of symptom remission.

An increasing body of evidence supports the use of family-based treatment (FBT) in medically stable outpatient presentations of adolescent anorexia nervosa, although there is relatively less research on adapting evidence-based treatment approaches in more intensive levels of patient care. The integration of FBT, which centrally leverages parental involvement in more intensive levels of care which typically require greater clinical management, requires careful consideration. We provide an overview of several key practical and theoretical considerations when adjusting the delivery of FBT across more intensive levels of patient care, providing clinical guidelines for the delivery of FBT while ensuring fidelity to the core theoretical tenets. Implications for clinical practice and future research are discussed.

There is a continued need to improve upon the efficacy and availability of treatments for anorexia nervosa. Family-based therapy for anorexia nervosa demonstrates strong empirical evidence; however, trained treatment providers are limited and a subsample of participants receiving the treatment fail to respond. The intensive family treatment program is a brief, time-limited, multi-family program that trains families of adolescents with eating disorders to oversee their adolescents' recovery at home by providing psychoeducation, skills training, and immersive practice over the course of a 5-day period. This article provide a description of the program by summarizing underlying theoretical principles and key therapeutic components.

Dialectical behavior therapy (DBT) and family-based treatment (FBT) are two evidence-based interventions that have been applied in the treatment of bulimia nervosa (BN) in adolescents. While DBT focuses on providing skills for coping with emotion dysregulation that often co-occurs with BN, FBT targets the normalization of eating patterns. The purpose of the current article is to introduce an integration of both treatments to provide a more comprehensive approach that targets the full scope of the disorder. We provide a review of the conceptual similarities and differences between FBT-BN and DBT along with strategies to guide a blended treatment approach. Given the strengths and limitations of either independent treatment, DBT and FBT-BN complement one another and together can address the range of symptoms and behaviors typically seen in adolescent BN.

Anorexia nervosa (AN) is a severe and debilitating disorder with significant medical and psychological sequelae. To date, there are no effective treatments for adults, resulting in high rates of chronicity, morbidity, and mortality. Recent advances in brain imaging research have led to an improved understanding of etiology and specific neurobiological mechanisms underlying symptoms. Despite this, there are no treatments focused on targeting symptoms using this empirically supported mechanistic understanding of the illness. Updated treatment approaches focused on targeting neurobiological mechanisms underlying core AN symptomatology are necessary to improve treatment out-comes for this population. Neurobiologically Enhanced With Family Eating Disorder Trait Response Treatment (NEW FED TR) is a neurobiologically informed treatment targeting key temperament constructs associated with the illness through the delivery of psychoeducation and skills training to patients and nominated carers.

Family therapy approaches have generated impressive empirical evidence in the treatment of adolescent eating disorders (EDs). However, the paucity of specialist treatment providers limits treatment uptake; therefore, our group developed the intensive family therapy (IFT)-a 5-day treatment based on the principles of family-based therapy for EDs. We retrospectively examined the long-term efficacy of IFT in both single-family (S-IFT) and multi-family (M-IFT) settings evaluating 74 eating disordered adolescents who underwent IFT at the University of California, San Diego, between 2006 and 2013. Full remission was defined as normal weight (≥ 95% of expected for sex, age, and height), Eating Disorder Examination Questionnaire (EDE-Q) global score within 1 SD of norms, and absence of binge-purging behaviours. Partial remission was defined as weight ≥ 85% of expected or ≥ 95% but with elevated EDE-Q global score and presence of binge-purging symptoms (

Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.

ObjectiveIn keeping with broader efforts to identify mediators and moderators of treatment outcome in anorexia nervosa, this pilot study investigated the association between collegial alliance, which refers to the perceived alliance between case-involved professionals, and treatment outcomes in adolescent patients undergoing family-based treatment (FBT) for anorexia nervosa.MethodThe self-reported collegial alliance scores of five FBT practitioners were collected, alongside weight- and cognitive-related outcomes for 29 consecutive cases of adolescent anorexia nervosa under their care.ResultsCollegial alliance discriminated between patients who dropped out of treatment and patients who completed treatment, t(27) = 3.68, p = .001, η(2)  = .33. Furthermore, there was a strong negative correlation between collegial alliance scores early on in treatment and disordered eating symptoms later in treatment, r(23) = -.67, p

Family therapy has featured in the treatment of adolescent eating disorders for over 40 years, and the evolution of family therapy approaches, through a variety of theoretical lenses, has been significant. For instance, the recent dissemination of family-based treatment has resulted in a growing number of controlled empirical trials which continue to inform and augment treatment outcomes. In addition, a burgeoning number of alternate approaches to family therapy for eating disorders leave clinicians with more clinical considerations in practicing family therapy for eating disorders. In this paper, we aim to review the recent developments in family therapy for adolescent eating disorders, underscoring the impact on clinical practice and the likely implications for future research.

BackgroundTotal knee arthroplasty (TKA) for juvenile idiopathic arthritis is rare but is nonetheless indicated for many patients with this disease. Few reports exist on the results of TKA in patients with juvenile idiopathic arthritis.Questions/purposesIt was sought to determine (1) survivorship and (2) functional outcomes of TKAs in patients with juvenile idiopathic arthritis.MethodsResults were combined from patients treated by experienced surgeons at five hospitals between 1979 and 2011. Two hundred nineteen patients (349 TKAs) were identified and contacted to survey their outcomes at a minimum followup of 2 years (mean, 12 ± 8 years; range, 2-33 years). The average age at surgery was 28.9 ± 9.7 years (range, 11-58 years). Data on revision surgery and ability to perform daily activities were collected.ResultsThe 10-year survivorship was 95%, decreasing to 82% by 20 years. At latest followup, 31 of 349 TKAs (8.9%) had been revised for either polyethylene failure or loosening (18 TKAs), infection (four), stiffness (three), periprosthetic fractures (two), bilateral amputation for vascular reasons (two), patellar resurfacing (one), and instability (one). Walking tolerance was unlimited in 49%, five to 10 blocks in 23%, and less than five blocks in 28%. Eleven percent could not manage stairs, and another 59% depended on railings. A cane was used by 12% and crutches by 7%; 12% were wheelchair-dependent.ConclusionsTKA survivorship in patients with juvenile idiopathic arthritis was inferior to that typically seen in younger patients with osteoarthritis or even rheumatoid arthritis confirming results of earlier studies with smaller patient numbers. This is especially disconcerting because younger patients require better durability of their TKAs.

ObjectivesThe Xq28 region containing IRAK1 and MECP2 has been identified as a risk locus for systemic lupus erythematosus (SLE) in previous genetic association studies. However, due to the strong linkage disequilibrium between IRAK1 and MECP2, it remains unclear which gene is affected by the underlying causal variant(s) conferring risk of SLE.MethodsWe fine-mapped ≥136 SNPs in a ∼227 kb region on Xq28, containing IRAK1, MECP2 and seven adjacent genes (L1CAM, AVPR2, ARHGAP4, NAA10, RENBP, HCFC1 and TMEM187), for association with SLE in 15 783 case-control subjects derived from four different ancestral groups.ResultsMultiple SNPs showed strong association with SLE in European Americans, Asians and Hispanics at p

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified >30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF-κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway.MethodsWe analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog TNIP2, in case-control populations of diverse ethnic origins. TNIP1, TNIP2, and TAX1BP1 were fine-mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European-ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of TNIP1 messenger RNA (mRNA) and ABIN1 protein in Epstein-Barr virus-transformed human B cell lines were analyzed by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively.ResultsWe found significant associations between SLE and genetic variants within TNIP1, but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified 2 independent risk haplotypes within TNIP1 in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of TNIP1 mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.ConclusionOur results confirm the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.

ObjectiveAmerican Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients.MethodsA total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).ResultsThe average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.ConclusionIn general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.

ObjectiveSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development.MethodsFifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsEvidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10(-5) and P = 4.73 × 10(-5) , respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r(2) = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10(-4) , OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10(-6) , OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model.ConclusionOur data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity.

Insulin from the beta-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes.