Publications by authors named "Kamryn T Eddy"

134 Publications

Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

Psychoneuroendocrinology 2021 Jul 28;129:105243. Epub 2021 Apr 28.

Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, United States of America; Department of Medicine, Harvard Medical School, Boston, MA, United States of America.

Background: Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC).

Methods: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10-22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal.

Results: Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037).

Conclusions: ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105243DOI Listing
July 2021

Validation of the nine item ARFID screen (NIAS) subscales for distinguishing ARFID presentations and screening for ARFID.

Int J Eat Disord 2021 Apr 22. Epub 2021 Apr 22.

Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: The Nine Item Avoidant/Restrictive Food Intake Disorder (ARFID) Screen (NIAS) has three subscales aligned with ARFID presentations but clinically validated cutoff scores have not been identified. We aimed to examine NIAS subscale (picky eating, appetite, fear) validity to: (1) capture clinically-diagnosed ARFID presentations; (2) differentiate ARFID from other eating disorders (other-ED); and (3) capture ARFID symptoms among individuals with ARFID, individuals with other-ED, and nonclinical participants.

Method: Participants included outpatients (ages 10-76 years; 75% female) diagnosed with ARFID (n = 49) or other-ED (n = 77), and nonclinical participants (ages 22-68 years; 38% female, n = 40). We evaluated criterion-related concurrent validity by conducting receiver operating curve (ROC) analyses to identify potential subscale cutoffs and by testing if cutoffs could capture ARFID with and without use of the Eating Disorder Examination-Questionnaire (EDE-Q).

Results: Each NIAS subscale had high AUC for capturing those who fit versus do not fit each ARFID presentation, resulting in proposed cutoffs of ≥10 (sensitivity = .97, specificity = .63), ≥9 (sensitivity = .86, specificity = .70), and ≥ 10 (sensitivity = .68, specificity = .89) on the NIAS-picky eating, NIAS-appetite, and NIAS-fear subscales, respectively. ARFID versus other-ED had high AUC on the NIAS-picky eating (≥10 proposed cutoff), but not NIAS-appetite or NIAS-fear subscales. NIAS subscale cutoffs had a high association with ARFID diagnosis, but only correctly classified other-ED in combination with EDE-Q Global <2.3.

Discussion: To screen for ARFID, we recommend using a screening tool for other-ED (e.g., EDE-Q) in combination with a positive score on any NIAS subscale (i.e., ≥10, ≥9, and/or ≥10 on the NIAS-picky eating, NIAS-appetite, and NIAS-fear subscales, respectively).
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http://dx.doi.org/10.1002/eat.23520DOI Listing
April 2021

Memory and Executive Function in Adolescent and Young Adult Females with Moderate to Severe Obesity Before and After Weight Loss Surgery.

Obes Surg 2021 Jul 7;31(7):3372-3378. Epub 2021 Apr 7.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

There is a global increase in the prevalence of severe obesity in females during adolescence, which is a critical period for neurocognitive development. An increasing number of adolescents and young adults are now undergoing weight loss surgery as a treatment strategy for obesity. In addition to metabolic complications, obesity has been linked to neurocognitive comorbidity, and studies exploring cognitive performance in adolescents with severe obesity and the impact of bariatric surgery on cognitive abilities are limited. Verbal memory and executive function were assessed cross-sectionally in 69 females with moderate to severe obesity and 24 females without obesity, 13-24 years old. In an exploratory analysis, cognitive changes were also assessed longitudinally over 12 months in a subset of 35 females with moderate to severe obesity following weight loss surgery (n = 21) or following usual care without surgery (n = 14). In cross-sectional analysis, females with moderate to severe obesity showed lower scores for short-term and long-term recall (verbal memory) and response inhibition and cognitive flexibility (executive function) than the comparison group, when adjusted for age and baseline intelligence. Females with moderate to severe obesity who underwent surgery showed significant weight loss but no improvement in verbal memory and executive function scores over 12 months compared with those who did not have surgery. Females with moderate to severe obesity demonstrate worse performance in tests of verbal memory and executive function than the comparison group without obesity. In addition, exploratory analyses provide no indication that weight loss surgery improves these observed cognitive decrements over a period of 12 months. Further studies are necessary to comprehensively evaluate changes in cognitive function following bariatric surgery.
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http://dx.doi.org/10.1007/s11695-021-05386-xDOI Listing
July 2021

Neurobiology of Avoidant/Restrictive Food Intake Disorder in Youth with Overweight/Obesity Versus Healthy Weight.

J Clin Child Adolesc Psychol 2021 Mar 26:1-14. Epub 2021 Mar 26.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School.

: Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight.: Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger.: Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [-45.09, -3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB.: Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.
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http://dx.doi.org/10.1080/15374416.2021.1894944DOI Listing
March 2021

Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.

J Clin Endocrinol Metab 2021 Jun;106(7):2021-2035

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Context: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency.

Objective: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes.

Design: Double-blind, randomized, placebo-controlled 12-month longitudinal study.

Participants: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study.

Intervention: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range.

Main Outcome Measures: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates.

Results: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups.

Conclusions: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
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http://dx.doi.org/10.1210/clinem/dgab145DOI Listing
June 2021

Network Analysis of Posttraumatic Stress and Eating Disorder Symptoms in a Community Sample of Adults Exposed to Childhood Abuse.

J Trauma Stress 2021 Jun 28;34(3):665-674. Epub 2020 Dec 28.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA.

Posttraumatic stress disorder (PTSD) and eating disorders (EDs) are individually debilitating and highly comorbid conditions. Childhood abuse is a prominent risk factor for PTSD and ED symptoms both individually and as a comorbid syndrome (PTSD-ED). There may be a functional association between comorbid PTSD-ED symptoms whereby disordered eating behaviors are used to avoid trauma-related thoughts and feelings. The current study used a network analytic approach to examine key associations between PTSD and ED symptom subscales (i.e., PCL-5 and EPSI, respectively) in a community sample of 120 adults who endorsed at least one experience of childhood abuse (i.e., physical, sexual, or emotional abuse; witnessing domestic violence). Participants completed an anonymous online survey using Amazon's Mechanical Turk Prime. We used three network analysis indices (i.e., strength centrality, key players, and bridge symptoms) to identify symptoms that may maintain the comorbid PTSD-ED network. The results indicated that reexperiencing symptoms had the highest strength centrality in the PTSD-ED network and bridged the PTSD and ED clusters. For ED, cognitive restraint was a bridge to all PTSD symptoms. Hyperarousal, negative alterations in cognitions and mood (NACM), and purging were key players, indicating they are integral to the network structure. If replicated in prospective studies, these results may indicate that reexperiencing and cognitive restraint are core drivers of PTSD-ED comorbidity, whereas hyperarousal, NACM, and purging may be downstream consequences maintaining the comorbid condition. Concurrent treatments that address PTSD and ED symptoms simultaneously may result in the best outcomes.
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http://dx.doi.org/10.1002/jts.22644DOI Listing
June 2021

Disorders of gut-brain interaction common among outpatients with eating disorders including avoidant/restrictive food intake disorder.

Int J Eat Disord 2021 Jun 26;54(6):952-958. Epub 2020 Nov 26.

Center for Neurointestinal Health, Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: Little research exists on Rome IV disorders of gut-brain interaction (DGBI; formerly called functional gastrointestinal disorders) in outpatients with eating disorders (EDs). These data are particularly lacking for avoidant/restrictive food intake disorder (ARFID), which shares core features with DGBI. We aimed to identify the frequency and nature of DGBI symptoms among outpatients with EDs.

Method: Consecutively referred pediatric and adult patients diagnosed with an ED (n = 168, 71% female, ages 8-76 years) in our tertiary care ED program between March 2017 and July 2019 completed a modified Rome IV Questionnaire for DGBI and psychopathology measure battery.

Results: The majority (n = 122, 72%) of participants reported at least one bothersome gastrointestinal symptom. Sixty-six (39%) met criteria for a DBGI, most frequently functional dyspepsia-post-prandial distress syndrome subtype (31%). DGBI were surprisingly less frequent among patients with ARFID (30%) versus EDs that are associated with shape or weight concerns (45%; X [1] = 3.61, p = .058, Cramer's V = .147). Among those with ARFID, DGBI presence was associated with the fear of aversive consequences prototype and multiple comorbid prototype presence.

Discussion: We demonstrated notable overlap between DGBI and EDs, particularly post-prandial distress symptoms. Further research is needed to examine if gastrointestinal symptoms predict or are a result of greater ED pathology, including ARFID prototypes.
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http://dx.doi.org/10.1002/eat.23414DOI Listing
June 2021

Cognitive-behavioral therapy for avoidant/restrictive food intake disorder: Feasibility, acceptability, and proof-of-concept for children and adolescents.

Int J Eat Disord 2020 10 9;53(10):1636-1646. Epub 2020 Aug 9.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: Little is known about the optimal treatment of avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate feasibility, acceptability, and proof-of-concept for cognitive-behavioral therapy for ARFID (CBT-AR) in children and adolescents.

Method: Males and females (ages 10-17 years) were offered 20-30 sessions of CBT-AR delivered in a family-based or individual format.

Results: Of 25 eligible individuals, 20 initiated treatment, including 17 completers and 3 dropouts. Using intent-to-treat analyses, clinicians rated 17 patients (85%) as "much improved" or "very much improved." ARFID severity scores (on the Pica, ARFID, and Rumination Disorder Interview) significantly decreased per both patient and parent report. Patients incorporated a mean of 16.7 (SD = 12.1) new foods from pre- to post-treatment. The underweight subgroup showed a significant weight gain of 11.5 (SD = 6.0) pounds, moving from the 10th to the 20th percentile for body mass index. At post-treatment, 70% of patients no longer met criteria for ARFID.

Discussion: This is the first study of an outpatient manualized psychosocial treatment for ARFID in older adolescents. Findings provide evidence of feasibility, acceptability, and proof-of-concept for CBT-AR. Randomized controlled trials are needed.
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http://dx.doi.org/10.1002/eat.23355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719612PMC
October 2020

Muscle dysmorphia: A systematic and meta-analytic review of the literature to assess diagnostic validity.

Int J Eat Disord 2020 10 1;53(10):1583-1604. Epub 2020 Aug 1.

Research School of Psychology, Australian National University, Canberra, Australia.

Objective: Although muscle dysmorphia (MD) is a new addition to DSM-5 as a specifier of body dysmorphic disorder (BDD), previous studies have treated MD as a stand-alone diagnosis. We aimed to assess the validity of MD as a stand-alone diagnosis via systematic and meta-analytic review of MD literature using both Robins and Guze criteria and additional criteria from Kendler.

Method: We performed a systematic search of ProQuest, PsycInfo, and PubMed databases for the period of January 1993 to October 2019 resulting in 40 papers to examine Robins and Guze's criteria (clinical picture) as well as those added by Kendler (antecedent validators; concurrent validators; predictive validators).

Results: We identified two distinct symptomatic presentations of MD using cluster analysis, a behavioral type and cognitive/behavioral type. For examining the concurrent validators, quantitative meta-analyses differentiated MD populations from controls; however, results were inconclusive in delineating MD from existing disorders. For assessing antecedent and predictive validators, the symptomatic profiles, treatment response, and familial links for MD were similar to those for BDD and for eating disorders.

Discussion: We found preliminary support for MD as a clinically valid presentation, but insufficient evidence to determine whether it is best categorized as a specifier of BDD or unique psychiatric condition.
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http://dx.doi.org/10.1002/eat.23349DOI Listing
October 2020

Behavioral symptoms of eating disorders among adopted adolescents and young adults in the United States: Findings from the Add Health survey.

Int J Eat Disord 2020 09 23;53(9):1515-1525. Epub 2020 Jul 23.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: More adopted individuals report experiencing general psychopathology, poor parental attachment, and early childhood eating difficulties than nonadopted individuals, yet little is known about disordered eating in this population. This study sought to describe the relationship between adoption status and behavioral eating-disorder (ED) symptoms, and to examine potential correlates of ED symptoms that are unique to adopted individuals.

Method: We examined data from adolescents and young adults from Waves 1 (n adopted = 561, nonadopted = 20,184), 2 (n adopted = 211, nonadopted = 14,525), and 3 (n adopted = 416, nonadopted = 14,754) of the National Longitudinal Study of Adolescent to Adult Health. ED symptom items included dieting, breakfast skipping, binge eating, extreme weight loss behaviors (EWLBs; i.e., self-induced vomiting, laxative use, diet pill use) and lifetime ED diagnosis.

Results: Compared to nonadopted individuals, adopted individuals were more likely to report EWLBs at Wave 2 and binge eating and lifetime ED diagnosis at Wave 3 (ps < .05). Among adopted individuals, contact with a biological parent was associated with higher rates of binge eating and lifetime ED diagnosis at Wave 3 (ps < .05), whereas age at adoption and having ever been in foster care were not associated with rates of ED symptoms.

Discussion: This study provides preliminary evidence that being adopted may be a risk factor for certain behavioral symptoms of EDs. Given the benefits of early detection and treatment of ED symptoms, mental health professionals working with adopted individuals should assess for disordered eating.
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http://dx.doi.org/10.1002/eat.23334DOI Listing
September 2020

Behavioral symptoms of eating disorders among adopted adolescents and young adults in the United States: Findings from the Add Health survey.

Int J Eat Disord 2020 09 23;53(9):1515-1525. Epub 2020 Jul 23.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: More adopted individuals report experiencing general psychopathology, poor parental attachment, and early childhood eating difficulties than nonadopted individuals, yet little is known about disordered eating in this population. This study sought to describe the relationship between adoption status and behavioral eating-disorder (ED) symptoms, and to examine potential correlates of ED symptoms that are unique to adopted individuals.

Method: We examined data from adolescents and young adults from Waves 1 (n adopted = 561, nonadopted = 20,184), 2 (n adopted = 211, nonadopted = 14,525), and 3 (n adopted = 416, nonadopted = 14,754) of the National Longitudinal Study of Adolescent to Adult Health. ED symptom items included dieting, breakfast skipping, binge eating, extreme weight loss behaviors (EWLBs; i.e., self-induced vomiting, laxative use, diet pill use) and lifetime ED diagnosis.

Results: Compared to nonadopted individuals, adopted individuals were more likely to report EWLBs at Wave 2 and binge eating and lifetime ED diagnosis at Wave 3 (ps < .05). Among adopted individuals, contact with a biological parent was associated with higher rates of binge eating and lifetime ED diagnosis at Wave 3 (ps < .05), whereas age at adoption and having ever been in foster care were not associated with rates of ED symptoms.

Discussion: This study provides preliminary evidence that being adopted may be a risk factor for certain behavioral symptoms of EDs. Given the benefits of early detection and treatment of ED symptoms, mental health professionals working with adopted individuals should assess for disordered eating.
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http://dx.doi.org/10.1002/eat.23334DOI Listing
September 2020

Developmental stage-dependent relationships between ghrelin levels and hippocampal white matter connections in low-weight anorexia nervosa and atypical anorexia nervosa.

Psychoneuroendocrinology 2020 09 23;119:104722. Epub 2020 May 23.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Introduction: Disruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown.

Methods: We evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20).

Results: FA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty.

Conclusions: In post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104722DOI Listing
September 2020

An investigation of distress tolerance and difficulties in emotion regulation in the drive for muscularity among women.

Body Image 2020 Jun 11;33:207-213. Epub 2020 May 11.

Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia.

Despite the negative emotional experiences that often accompany the pursuit of an idealized appearance, we know little about emotion regulation in the context of female drive for muscularity. To address this knowledge gap, we examined whether distress tolerance and difficulties in emotion regulation were significantly associated with the drive for toned muscularity among women. In this study, 221 Australian university women completed an online survey assessing drive for muscularity, distress tolerance, and emotion regulation difficulties. Results revealed that low distress tolerance and emotion regulation difficulties were positively associated with drive for muscularity attitudes and behaviors, after controlling for body mass index and general negative affect. Our findings suggest that women with a range of distress tolerance and emotion regulation difficulties, particularly the urgent need to regulate, and non-acceptance of, distress may experience a higher drive for muscularity. This study provides preliminary evidence that specific aspects of distress tolerance and poor emotion regulation may be promising targets in prevention and treatment interventions aimed to address the excessive drive for muscularity among women.
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http://dx.doi.org/10.1016/j.bodyim.2020.03.004DOI Listing
June 2020

Medical comorbidities and endocrine dysfunction in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

Int J Eat Disord 2020 04 21;53(4):631-636. Epub 2020 Mar 21.

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: To improve our understanding of medical complications and endocrine alterations in patients with low-weight avoidant/restrictive food intake disorder (ARFID) and how they may differ from those in anorexia nervosa (AN) and healthy controls (HC).

Method: We performed an exploratory cross-sectional study comparing low-weight females with ARFID (n = 20) with females with AN (n = 42) and HC (n = 49) with no history of an eating disorder.

Results: We found substantial overlap in medical comorbidities and endocrine features in ARFID and AN, but with earlier onset of aberrant eating behaviors in ARFID. We also observed distinct medical and endocrine alterations in ARFID compared to AN, such as a greater prevalence of asthma, a lower number of menses missed in the preceding 9 months, higher total T3 levels, and lower total T4 : total T3 ratio; these differences persisted after adjusting for age and might reflect differences in pathophysiology, acuity of weight fluctuations, and/or nutritional composition of food consumed.

Conclusion: These results highlight the need for prompt diagnosis and intensive therapeutic intervention from disease onset in ARFID.
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http://dx.doi.org/10.1002/eat.23261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184800PMC
April 2020

Identifying duration criteria for eating-disorder remission and recovery through intensive modeling of longitudinal data.

Int J Eat Disord 2020 08 27;53(8):1224-1233. Epub 2020 Feb 27.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objective: Outcome states, such as remission and recovery, include specific duration criteria for which individuals must be asymptomatic. Ideally, duration criteria provide predictive validity to outcome states by reducing symptom-return risk. However, available research is insufficient for deriving specific recommendations for remission or recovery duration criteria for eating disorders.

Method: We intensively modeled the relation between duration criteria length and rates of remission, recovery, and subsequent symptom return in longitudinal data from a treatment-seeking sample of women with anorexia nervosa (AN) and bulimia nervosa (BN). We hypothesized that the length of the duration criterion would be inversely associated with both rates of remission and recovery and with subsequent rates of symptom return.

Results: Generalized estimating equations supported our hypotheses for all investigated eating-disorder features except for symptom return when using the Psychiatric Status Rating for AN.

Discussion: We recommend that 6 months be used for remission definitions applied to binge eating, purging, and BN symptom composite measures, whereas no duration criteria be used for low weight and AN symptom composites. We further recommend that 6 months be used for recovery definitions applied to BN symptom composites and AN symptom composites, whereas 18 months be used for individual symptoms of binge eating, purging, and low weight. The adoption of these duration criteria into comprehensive definitions of remission and recovery will increase their predictive validity, which in turn, maximizes their utility.
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http://dx.doi.org/10.1002/eat.23249DOI Listing
August 2020

Changes in appetite-regulating hormones following food intake are associated with changes in reported appetite and a measure of hedonic eating in girls and young women with anorexia nervosa.

Psychoneuroendocrinology 2020 03 23;113:104556. Epub 2019 Dec 23.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, United States; Division of Pediatric Endocrinology, Massachusetts General Hospital for Children and Harvard Medical School, United States. Electronic address:

Background: Females with anorexia nervosa (AN) have higher ghrelin and peptide YY (PYY) and lower brain-derived neurotropic factor (BDNF) levels than controls, and differ in their perception of hunger cues. Studies have not examined appetite-regulating hormones in the context of homeostatic and hedonic appetite in AN.

Objective: To examine whether alterations in appetite-regulating hormones following a standardized meal are associated with homeostatic and hedonic appetite in young females with AN vs. controls.

Methods: 68 females (36 AN, 32 controls) 10-22 years old were enrolled. Ghrelin, PYY and BDNF levels were assessed before, and 30, 60 and 120 min following a 400-kilocalorie standardized breakfast. Visual Analog Scales (VAS) assessing prospective food consumption, hunger, satiety, and hedonic appetite were administered before and 20 min after breakfast. A Cookie Taste Test (CTT) was conducted after a snack as a measure of hedonic eating behavior ∼3 h after breakfast.

Results: AN had higher fasting ghrelin and PYY, and lower fasting BDNF (p = 0.001, 0.002 and 0.044 respectively) than controls. Following breakfast (over 120 min), ghrelin and PYY area under the curve (AUC) were higher, while BDNF AUC was lower in AN vs. controls (p = 0.007, 0.017 and 0.020 respectively). Among AN (but not controls), reductions in ghrelin and increases in PYY in the first 30-minutes following breakfast were associated with reductions in VAS scores for prospective food consumption. AN consumed fewer calories during the CTT vs. controls (p < 0.0001). In AN (particularly AN-restrictive subtype), BDNF AUC was positively associated with kilocalories consumed during the CTT CONCLUSIONS: In young females with AN, changes in ghrelin and PYY following food intake are associated with reductions in a prospective measure of food consumption, while reductions in BDNF are associated with reduced hedonic food intake. Further studies are necessary to better understand the complex interplay between appetite signals and eating behaviors in AN.
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http://dx.doi.org/10.1016/j.psyneuen.2019.104556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080573PMC
March 2020

Changes in appetite-regulating hormones following food intake are associated with changes in reported appetite and a measure of hedonic eating in girls and young women with anorexia nervosa.

Psychoneuroendocrinology 2020 03 23;113:104556. Epub 2019 Dec 23.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, United States; Division of Pediatric Endocrinology, Massachusetts General Hospital for Children and Harvard Medical School, United States. Electronic address:

Background: Females with anorexia nervosa (AN) have higher ghrelin and peptide YY (PYY) and lower brain-derived neurotropic factor (BDNF) levels than controls, and differ in their perception of hunger cues. Studies have not examined appetite-regulating hormones in the context of homeostatic and hedonic appetite in AN.

Objective: To examine whether alterations in appetite-regulating hormones following a standardized meal are associated with homeostatic and hedonic appetite in young females with AN vs. controls.

Methods: 68 females (36 AN, 32 controls) 10-22 years old were enrolled. Ghrelin, PYY and BDNF levels were assessed before, and 30, 60 and 120 min following a 400-kilocalorie standardized breakfast. Visual Analog Scales (VAS) assessing prospective food consumption, hunger, satiety, and hedonic appetite were administered before and 20 min after breakfast. A Cookie Taste Test (CTT) was conducted after a snack as a measure of hedonic eating behavior ∼3 h after breakfast.

Results: AN had higher fasting ghrelin and PYY, and lower fasting BDNF (p = 0.001, 0.002 and 0.044 respectively) than controls. Following breakfast (over 120 min), ghrelin and PYY area under the curve (AUC) were higher, while BDNF AUC was lower in AN vs. controls (p = 0.007, 0.017 and 0.020 respectively). Among AN (but not controls), reductions in ghrelin and increases in PYY in the first 30-minutes following breakfast were associated with reductions in VAS scores for prospective food consumption. AN consumed fewer calories during the CTT vs. controls (p < 0.0001). In AN (particularly AN-restrictive subtype), BDNF AUC was positively associated with kilocalories consumed during the CTT CONCLUSIONS: In young females with AN, changes in ghrelin and PYY following food intake are associated with reductions in a prospective measure of food consumption, while reductions in BDNF are associated with reduced hedonic food intake. Further studies are necessary to better understand the complex interplay between appetite signals and eating behaviors in AN.
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http://dx.doi.org/10.1016/j.psyneuen.2019.104556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080573PMC
March 2020

Co-occurrence of Avoidant/Restrictive Food Intake Disorder and Traditional Eating Psychopathology.

J Am Acad Child Adolesc Psychiatry 2020 02 26;59(2):209-212. Epub 2019 Nov 26.

Lawson are with Harvard Medical School, Boston, MA; Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston.

Avoidant/restrictive food intake disorder (ARFID) is a feeding/eating disorder introduced in the fifth edition of the DSM-5 that is characterized by inadequate volume and/or variety of food intake. ARFID represents an expansion of the prior DSM-IV disorder "Feeding Disorder of Early Childhood" that can be diagnosed across the lifespan.DSM-5 clearly states that ARFID cannot be diagnosed in the context of significant shape/weight concerns and associated behaviors. However, our clinical team has observed multiple instances in which adolescent girls have presented with frank ARFID and simultaneously reported, or ultimately developed, traditional eating-disorder psychopathology. The following two cases are representative of the most common presentations of this diagnostic overlap that we have seen. We discuss possible reasons for this overlap and suggest two revisions to DSM criteria that may help in treatment planning for this unexpected comorbidity. Each patient provided written consent for her case to be included.
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http://dx.doi.org/10.1016/j.jaac.2019.09.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380203PMC
February 2020

Behavioral inhibition moderates the association between overvaluation of shape and weight and noncompensatory purging in eating disorders.

Int J Eat Disord 2020 01 23;53(1):143-148. Epub 2019 Nov 23.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts.

Objective: The cognitive-behavioral therapy (CBT) model of eating disorders suggests that compensatory purging behaviors (e.g., self-induced vomiting, inappropriate laxative use) are primarily driven by binge eating. However, many individuals endorse purging in the absence of binge eating (i.e., noncompensatory purging [NCP]). Research is needed to understand why some individuals purge in the absence of objective or subjective binge-eating episodes.

Method: Given the importance of overvaluation of shape/weight in the CBT model, and the existing evidence linking temperamental characteristics like behavioral inhibition (i.e., the tendency to withdraw in response to threat cues) with purging in general, we tested whether behavioral inhibition moderated the relationship between overvaluation of shape/weight and NCP in a sample of individuals in a residential eating disorder treatment center (N = 143).

Results: Overvaluation was more strongly related to NCP in individuals with high (relative to low) levels of behavioral inhibition. Among individuals low in behavioral inhibition, overvaluation predicted engagement in NCP to a much weaker extent.

Discussion: For those high (relative to low) in behavioral inhibition, both emotional avoidance and overvaluation may be important targets in the treatment of NCP, particularly in the absence of binge eating.
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http://dx.doi.org/10.1002/eat.23195DOI Listing
January 2020

Behavioral inhibition moderates the association between overvaluation of shape and weight and noncompensatory purging in eating disorders.

Int J Eat Disord 2020 01 23;53(1):143-148. Epub 2019 Nov 23.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts.

Objective: The cognitive-behavioral therapy (CBT) model of eating disorders suggests that compensatory purging behaviors (e.g., self-induced vomiting, inappropriate laxative use) are primarily driven by binge eating. However, many individuals endorse purging in the absence of binge eating (i.e., noncompensatory purging [NCP]). Research is needed to understand why some individuals purge in the absence of objective or subjective binge-eating episodes.

Method: Given the importance of overvaluation of shape/weight in the CBT model, and the existing evidence linking temperamental characteristics like behavioral inhibition (i.e., the tendency to withdraw in response to threat cues) with purging in general, we tested whether behavioral inhibition moderated the relationship between overvaluation of shape/weight and NCP in a sample of individuals in a residential eating disorder treatment center (N = 143).

Results: Overvaluation was more strongly related to NCP in individuals with high (relative to low) levels of behavioral inhibition. Among individuals low in behavioral inhibition, overvaluation predicted engagement in NCP to a much weaker extent.

Discussion: For those high (relative to low) in behavioral inhibition, both emotional avoidance and overvaluation may be important targets in the treatment of NCP, particularly in the absence of binge eating.
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http://dx.doi.org/10.1002/eat.23195DOI Listing
January 2020

Cognitive rigidity and heightened attention to detail occur transdiagnostically in adolescents with eating disorders.

Eat Disord 2019 Nov 1:1-13. Epub 2019 Nov 1.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.

Cognitive inflexibility and attention to detail bias represent a promising target in eating disorder (ED) treatment. While prior research has found that adults with eating disorders exhibit significant cognitive inflexibility and heightened attention to detail, less is known about these cognitive impairments among adolescents, and across EDs transdiagnostically. To address this gap, adolescent females ( = 143) from a residential ED program with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorder completed the Detail and Flexibility Questionnaire (DFlex) and measures of ED and general psychopathology. Transdiagnostically, adolescents with EDs scored higher than an archival sample of healthy control adolescents on both cognitive rigidity ( < .001; Cohen's = 1.92) and attention to detail ( < .001; Cohen's = 1.16). These cognitive impairments were significantly associated with severity of eating pathology, and these relationships existed independent of age, duration of illness, or body mass index (BMI). Our findings suggest cognitive inflexibility and heightened attention to detail occur transdiagnostically in adolescents with eating disorders and are unlikely to be a scar of the disorder. Future prospective research is needed to determine whether these cognitive styles represent an endophenotype of eating disorders.
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http://dx.doi.org/10.1080/10640266.2019.1656470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192764PMC
November 2019

Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Adult Neurogastroenterology Patients.

Clin Gastroenterol Hepatol 2020 08 24;18(9):1995-2002.e1. Epub 2019 Oct 24.

Harvard Medical School, Boston, Massachusetts; Center for Neurointestinal Health, Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.

Background & Aims: Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder that is characterized by avoidant or restrictive eating not primarily motivated by body shape or weight concerns. We aimed to determine the frequency of ARFID symptoms and study its characteristics and associated gastrointestinal symptoms.

Methods: We conducted a retrospective review of charts from 410 consecutive referrals (ages, 18-90 y; 73.0% female) to a tertiary care center for neurogastroenterology examination, from January through December 2016. Blinded coders (n = 4) applied Diagnostic and Statistical Manual of Mental Disorders, 5th edition, criteria for ARFID, with substantial diagnostic agreement (κ = 0.66).

Results: Twenty-six cases (6.3%) met the full criteria for ARFID and 71 cases (17.3%) had clinically significant avoidant or restrictive eating behaviors with insufficient information for a definitive diagnosis of ARFID. Of patients with ARFID symptoms (n = 97), 90 patients (92.8%) cited fear of gastrointestinal symptoms as motivation for their avoidant or restrictive eating. A series of binary logistic regressions showed that the likelihood of having ARFID symptoms increased significantly in patients with eating- or weight-related complaints (odds ratio [OR], 5.09; 95% CI, 2.54-10.21); with dyspepsia, nausea, or vomiting (OR, 3.59; 95% CI, 2.04-6.32); with abdominal pain (OR, 4.72; 95% CI, 1.87-11.81); or with lower GI diagnoses (OR, 2.40; 95% CI, 1.34-4.32).

Conclusions: In a retrospective study of patients undergoing neurogastroenterology examinations, we found ARFID symptoms to be related most frequently to fear of gastrointestinal symptoms. Patients undergoing neurogastroenterology or motility examinations should be evaluated for symptoms of ARFID, particularly when providers consider dietary interventions.
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http://dx.doi.org/10.1016/j.cgh.2019.10.030DOI Listing
August 2020

Negative psychological correlates of the pursuit of muscularity among women.

Int J Eat Disord 2019 11 14;52(11):1326-1331. Epub 2019 Oct 14.

Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia.

Objective: There is increasing public and scientific focus on women's pursuit of a muscular and toned appearance. However, the psychological correlates of women's drive for muscularity are currently unclear. Therefore, we examined the associations of drive for muscularity with four important negative psychological indices among women: eating disorder (ED) symptoms, and symptoms of depression, anxiety, and stress.

Method: A sample of 221 university women completed an online survey that included measures assessing the aforementioned constructs.

Results: Drive for muscularity evidenced positive associations with all negative psychological indices, except for anxiety. Muscularity-oriented attitudes, as opposed to behaviors, demonstrated the strongest associations with ED and depression symptoms.

Discussion: Our findings make a novel contribution to the scant literature by demonstrating that women who endorse attitudes and/or behaviors geared toward attaining the female muscular ideal may be susceptible to experiencing ED symptoms and negative emotional states. This study provides preliminary evidence that muscularity-oriented attitudes, in particular, may be a promising target for the treatment of EDs and negative emotional states in women with a preoccupation toward muscularity.
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http://dx.doi.org/10.1002/eat.23178DOI Listing
November 2019

Effects of Estrogen Replacement on Bone Geometry and Microarchitecture in Adolescent and Young Adult Oligoamenorrheic Athletes: A Randomized Trial.

J Bone Miner Res 2020 02 7;35(2):248-260. Epub 2019 Nov 7.

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy-five OAs (ages 14 to 25 years) were randomized to (i) a 100-μg 17β-estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high-resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol-containing pills, particularly at the tibia. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064307PMC
February 2020

A Diet High in Processed Foods, Total Carbohydrates and Added Sugars, and Low in Vegetables and Protein Is Characteristic of Youth with Avoidant/Restrictive Food Intake Disorder.

Nutrients 2019 Aug 27;11(9). Epub 2019 Aug 27.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA.

Avoidant/restrictive food intake disorder (ARFID) is characterized in part by limited dietary variety, but dietary characteristics of this disorder have not yet been systematically studied. Our objective was to examine dietary intake defined by diet variety, macronutrient intake, and micronutrient intake in children and adolescents with full or subthreshold ARFID in comparison to healthy controls. We collected and analyzed four-day food record data for 52 participants with full or subthreshold ARFID, and 52 healthy controls, aged 9-22 years. We examined frequency of commonly reported foods by logistic regression and intake by food groups, macronutrients, and micronutrients between groups with repeated-measures ANOVA. Participants with full or subthreshold ARFID did not report any fruit or vegetable category in their top five most commonly reported food categories, whereas these food groups occupied three of the top five groups for healthy controls. Vegetable and protein intake were significantly lower in full or subthreshold ARFID compared to healthy controls. Intakes of added sugars and total carbohydrates were significantly higher in full or subthreshold ARFID compared to healthy controls. Individuals with full or subthreshold ARFID had lower intake of vitamins K and B12, consistent with limited vegetable and protein intake compared to healthy controls. Our results support the need for diet diversification as part of therapeutic interventions for ARFID to reduce risk for nutrient insufficiencies and related complications.
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http://dx.doi.org/10.3390/nu11092013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770555PMC
August 2019

Maternal Eating Disorders and Eating Disorder Treatment Among Girls in the Growing Up Today Study.

J Adolesc Health 2019 10 2;65(4):469-475. Epub 2019 Jul 2.

Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island; Department of Pediatrics, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Purpose: The aim of the study was to assess whether girls with mothers who have had an eating disorder (ED) have greater odds of developing ED symptoms and whether girls with ED symptoms have greater odds of receiving ED treatment if their mothers have an ED history.

Methods: Data came from 3,649 females in the Growing Up Today Study. Data were collected via questionnaires that were mailed every 12-24 months from 1996 to 2013. Girls who reported on ED treatment in 2013 and whose mothers completed a questionnaire in 2004 about maternal and child EDs were included in main analyses. Generalized estimating equations were used.

Results: Among complete cases, 28.3% of girls reported symptoms meeting criteria for an ED in at least 1 year and, of these, 12.4% reported receiving treatment. Girls with mothers with ED histories had nearly twice the odds of reporting symptoms of any ED (adjusted odds ratio: 1.89; 95% confidence interval: 1.38-2.60). Girls who reported symptoms meeting criteria for any ED had more than twice the odds of reporting treatment if their mother had an ED history (adjusted odds ratio: 2.23; 95% confidence interval: 1.25-3.99).

Conclusions: Girls with mothers with an ED history had greater odds of both reporting ED symptoms and receiving ED treatment. Screening both girls and their mothers for current or previous disordered eating may be important for the prevention and detection of ED symptoms. More research is needed to examine reasons for the association between maternal ED history and ED treatment in girls.
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http://dx.doi.org/10.1016/j.jadohealth.2019.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755056PMC
October 2019

Disrupted Oxytocin-Appetite Signaling in Females With Anorexia Nervosa.

J Clin Endocrinol Metab 2019 10;104(10):4931-4940

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.

Context: In healthy females, oxytocin levels decrease postmeal, corresponding to increased satiety. The postprandial response of oxytocin in females with anorexia nervosa (AN)/atypical AN is unknown.

Objectives: To determine the pattern of postprandial serum oxytocin levels in females with AN/atypical AN, relationship with appetite, and effect of weight, eating behavior, and endogenous estrogen status.

Design: Cross-sectional.

Setting: Clinical research center.

Participants: 67 women (36 with AN [<85% expected body weight (EBW)]; 31 with atypical AN [≥ 85% EBW)]), age 22.4 ± 0.9 (mean ± SEM) years, categorized by weight, restricting vs binge/purge behavior, and estrogen status.

Interventions: Standardized mixed meal.

Main Outcome Measurements: Blood sampling for oxytocin occurred fasting and 30, 60, and 120 minutes postmeal. Subjective appetite was assessed using visual analog scales.

Results: In females with AN/atypical AN, oxytocin levels decreased from fasting to 60 (P = 0.002) and 120 (P = 0.005) minutes postmeal. The decrease in oxytocin from fasting to 120 minutes was greater in females with atypical AN than AN (P = 0.027) and did not differ by restricting vs binge/purge behavior or estrogen status. Controlling for caloric intake, the decrease in oxytocin was inversely related to the decrease in hunger postmeal in females with atypical AN (P = 0.04).

Conclusions: In females with AN/atypical AN, oxytocin levels decrease postmeal, as established in healthy females. Weight, but not restricting vs binge/purging nor endogenous estrogen status, affects postprandial oxytocin levels. The postprandial change in serum oxytocin levels is related to appetite in females with atypical AN only, suggesting a disconnect between oxytocin secretion and appetite in the undernourished state.
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http://dx.doi.org/10.1210/jc.2019-00926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734487PMC
October 2019

Differences in Trabecular Plate and Rod Structure in Premenopausal Women Across the Weight Spectrum.

J Clin Endocrinol Metab 2019 10;104(10):4501-4510

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.

Context: Premenopausal women with anorexia nervosa (AN) and obesity (OB) have elevated fracture risk. More plate-like and axially aligned trabecular bone, assessed by individual trabeculae segmentation (ITS), is associated with higher estimated bone strength. Trabecular plate and rod structure has not been reported across the weight spectrum.

Objective: To investigate trabecular plate and rod structure in premenopausal women.

Design: Cross-sectional study.

Setting: Clinical research center.

Participants: A total of 105 women age 21 to 46 years: (i) women with AN (n = 46), (ii) eumenorrheic lean healthy controls (HCs) (n = 29), and (iii) eumenorrheic women with OB (n = 30).

Measures: Trabecular microarchitecture by ITS.

Results: Mean age (±SD) was similar (28.9 ± 6.3 years) and body mass index differed (16.7 ± 1.8 vs 22.6 ± 1.4 vs 35.1 ± 3.3 kg/m2; P < 0.0001) across groups. Bone was less plate-like and axially aligned in AN (P ≤ 0.01) and did not differ between OB and HC. After controlling for weight, plate and axial bone volume fraction and plate number density were lower in OB vs HC; some were lower in OB than AN (P < 0.05). The relationship between weight and plate variables was quadratic (R = 0.39 to 0.70; P ≤ 0.0006) (i.e., positive associations were attenuated at high weight). Appendicular lean mass and IGF-1 levels were positively associated with plate variables (R = 0.27 to 0.67; P < 0.05). Amenorrhea was associated with lower radial plate variables than eumenorrhea in AN (P < 0.05).

Conclusions: In women with AN, trabecular bone is less plate-like. In women with OB, trabecular plates do not adapt to high weight. This is relevant because trabecular plates are associated with greater estimated bone strength. Higher muscle mass and IGF-1 levels may mitigate some of the adverse effects of low weight or excess adiposity on bone.
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http://dx.doi.org/10.1210/jc.2019-00843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735760PMC
October 2019

A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women With Anorexia Nervosa.

J Clin Endocrinol Metab 2019 10;104(10):4347-4355

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.

Context: Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity.

Objective: To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN.

Design: Double-blind, randomized, placebo-controlled trial.

Setting: Clinical research center.

Participants: Ninety women, 18 to 45 years, with AN and free testosterone levels below the median for healthy women.

Intervention: Transdermal testosterone, 300 μg daily, or placebo patch for 24 weeks.

Main Outcome Measures: Primary end point: body mass index (BMI). Secondary end points: depression symptom severity [Hamilton Depression Rating Scale (HAM-D)], anxiety symptom severity [Hamilton Anxiety Rating Scale (HAM-A)], and eating disorder psychopathology and behaviors.

Results: Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and 0.5 ± 1.1 kg/m2 in the placebo group (P = 0.03) over 24 weeks. At 4 weeks, there was a trend toward a greater decrease in HAM-D score (P = 0.09) in the testosterone vs placebo group. At 24 weeks, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D: -2.9 ± 4.9 (testosterone) vs -3.0 ± 5.0 (placebo), P = 0.72; HAM-A: -4.5 ± 5.3 (testosterone) vs -4.3 ± 4.4 (placebo), P = 0.25]. There were no significant differences in eating disorder scores between groups. Testosterone therapy was safe and well tolerated with no increase in androgenic side effects compared with placebo.

Conclusion: Low-dose testosterone therapy for 24 weeks was associated with less weight gain-and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms-compared with placebo in women with AN.
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http://dx.doi.org/10.1210/jc.2019-00828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736210PMC
October 2019

Evaluation and Treatment of Avoidant/Restrictive Food Intake Disorder (ARFID) in Adolescents.

Curr Pediatr Rep 2018 Jun 16;6(2):107-113. Epub 2018 Apr 16.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital.

Purpose Of Review: Avoidant/restrictive food intake disorder (ARFID) was added to the psychiatric nomenclature in 2013. However, youth with ARFID often present first to medical- rather than psychiatric-settings, making its evaluation and treatment relevant to pediatricians.

Recent Findings: ARFID is defined by limited volume or variety of food intake motivated by sensory sensitivity, fear of aversive consequences, or lack of interest in food or eating, and associated with medical, nutritional, and/or psychosocial impairment. It appears to be as common as anorexia nervosa and bulimia nervosa and can occur in individuals of all ages. ARFID is heterogeneous in presentation and may require both medical and psychological management.

Summary: Pediatricians should be aware of the diagnostic criteria for ARFID and the possibility that these patients may require medical intervention and referral for psychological treatment. The neurobiology underlying ARFID is unknown, and novel treatments are currently being tested.
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http://dx.doi.org/10.1007/s40124-018-0162-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534269PMC
June 2018