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

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.

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

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.

Eating disorder recovery is associated with absence of major depressive disorder and substance use disorders at 22-year longitudinal follow-up.

BACKGROUND: Psychiatric comorbidity is common in eating disorders (EDs) and associated with poor outcomes, including increased risk for relapse and premature death. Yet little is known about comorbidity following ED recovery. METHODS: We examined two common comorbidities, major depressive disorder (MDD) and substance use disorder (SUD), in adult women with intake diagnoses of anorexia nervosa and bulimia nervosa who participated in a 22-year longitudinal study. One hundred and seventy-six of 228 surviving participants (77.2%) were interviewed 22 years after study entry using the Eating Disorders Longitudinal Interval Follow-up Evaluation to assess ED recovery status. Sixty-four percent (n = 113) were recovered from their ED. The Structured Clinical Interview for DSM-IV was used to assess MDD and SUD at 22 years. RESULTS: At 22-year follow-up, 28% (n = 49) met criteria for MDD, and 6% (n = 11) met criteria for SUD. Those who recovered from their ED were 2.17 times more likely not to have MDD at 22-year follow-up (95% CI [1.10, 4.26], p = .023) and 5.33 times more likely not to have a SUD at 22-year follow-up than those who had not recovered from their ED (95% CI [1.36, 20.90], p = .008). CONCLUSION: Compared to those who had not fully recovered from their ED, those who had recovered were twice as likely not to be diagnosed with MDD in the past year and five times as likely not to be diagnosed with SUDs in the past year. These findings provide evidence that long-term recovery from EDs is associated with recovery from or absence of these common major comorbidities. Because comorbidity in EDs can predict poor outcomes, including greater risk for relapse and premature death, our findings of reduced risk for psychiatric comorbidity following recovery at long-term follow-up is cause for optimism.

Predictors of long-term recovery in anorexia nervosa and bulimia nervosa: Data from a 22-year longitudinal study.

OBJECTIVE: The objective of this study was to investigate predictors of long-term recovery from eating disorders 22 years after entry into a longitudinal study. METHOD: One hundred and seventy-six of the 228 surviving participants (77.2%) were re-interviewed 20-25 years after study entry using the Longitudinal Interval Follow-up Evaluation to assess ED recovery. The sample consisted of 100 women diagnosed with anorexia nervosa (AN) and 76 with bulimia nervosa (BN) at study entry. RESULTS: A comorbid diagnosis of major depression at the start of the study strongly predicted having a diagnosis of AN-Restricting type at the 22-year assessment. A higher body mass index (BMI) at study intake decreased the odds of being diagnosed with AN-Binge Purge type, relative to being recovered, 22 years later. The only predictor that increased the likelihood of having a diagnosis of BN at the 22-year assessment was the length of time during the study when the diagnostic criteria for BN were met. CONCLUSIONS: Together, these results indicate that the presence and persistence of binge eating and purging behaviors were poor prognostic indicators and that comorbidity with depression is particularly pernicious in AN. Treatment providers might pay particular attention to these issues in an effort to positively influence recovery over the long-term.

Will I get fat? 22-year weight trajectories of individuals with eating disorders.

OBJECTIVE: For some, fat phobia or fear of uncontrollable weight gain is diagnostic of eating disorders, often inhibiting treatment engagement and predicting symptom relapse. Prior research has reported weight changes at infrequent or long intervals, but rate, shape, and magnitude of long-term changes remain unknown. Our study examined 22-year longitudinal trajectories of body mass index (BMI) in women with anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: Participants were followed over 10 years (N = 225) and at 22-year follow-up (N = 175). Using latent growth curves, we examined: (1) shape and rate of intra-individual BMI change over 10 years; (2) predictors of BMI change over 10 years, (3) 22-year BMI outcomes; and (4) BMI changes over 10 years as predictors of 22-year BMI. RESULTS: The best-fitting model captured overall intra-individual rates of BMI change in three intervals, showing moderate rate of BMI increase from intake to year 2, modest increase from year 2 to 5, and plateau from year 5 to 10. At 22 years, 14% were underweight, 69% were normal weight, and only 17% were overweight or obese. Greater increases from intake to year 2 predicted higher BMI at 22 years (ß = 0.43, p < 0.01) and were predicted by intake diagnosis of AN-restricting (ß = 0.31, p < 0.01) or AN-binge eating/purging (ß = 0.29, p < 0.01). DISCUSSION: BMI increased most rapidly during earlier years of the study for those with lower weight at study intake (i. e., AN) and plateaued over time, settling in the normal range for most. Psychoeducation about expected BMI trajectory may challenge patients' long-term fat phobic predictions.

Recovery From Anorexia Nervosa and Bulimia Nervosa at 22-Year Follow-Up.

OBJECTIVE: The course of eating disorders is often protracted, with fewer than half of adults achieving recovery from anorexia nervosa or bulimia nervosa. Some argue for palliative management when duration exceeds a decade, yet outcomes beyond 20 years are rarely described. This study investigates early and long-term recovery in the Massachusetts General Hospital Longitudinal Study of Anorexia and Bulimia Nervosa. METHODS: Females with DSM-III-R/DSM-IV anorexia nervosa or bulimia nervosa were assessed at 9 and at 20 to 25 years of follow-up (mean [SD] = 22.10 [1.10] years; study initiated in 1987, last follow-up conducted in 2013) via structured clinical interview (Longitudinal Interval Follow-Up Evaluation of Eating Disorders [LIFE-EAT-II]). Seventy-seven percent of the original cohort was re-interviewed, and multiple imputation was used to include all surviving participants from the original cohort (N = 228). Kaplan-Meier curves estimated recovery by 9-year follow-up, and McNemar test examined concordance between recovery at 9-year and 22-year follow-up. RESULTS: At 22-year follow-up, 62.8% of participants with anorexia nervosa and 68.2% of participants with bulimia nervosa recovered, compared to 31.4% of participants with anorexia nervosa and 68.2% of participants with bulimia nervosa by 9-year follow-up. Approximately half of those with anorexia nervosa who had not recovered by 9 years progressed to recovery at 22 years. Early recovery was associated with increased likelihood of long-term recovery in anorexia nervosa (odds ratio [OR] = 10.5; 95% CI, 3.77-29.28; McNemar χ²1 = 31.39; P < .01) but not in bulimia nervosa (OR = 1.0; 95% CI, 0.49-2.05; McNemar χ²1 = 0; P = 1.0). CONCLUSION: At 22 years, approximately two-thirds of females with anorexia nervosa and bulimia nervosa were recovered. Recovery from bulimia nervosa happened earlier, but recovery from anorexia nervosa continued over the long term, arguing against the implementation of palliative care for most individuals with eating disorders.

Re-examining premature mortality in anorexia nervosa: a meta-analysis redux.

Anorexia nervosa (AN) is reported to have the highest premature mortality of any psychiatric disorder, but recent meta-analyses may have inflated estimates. We sought to re-estimate mortality after methodological corrections and to identify predictors of mortality. We included 41 cohorts from 40 peer-reviewed studies published between 1966 and 2010. Methods included double data extraction, log-linear regression with an over-dispersed Poisson model, and all-cause and suicide-specific standardized mortality ratios (SMRs), with 95% Poisson confidence intervals. Participants with AN were 5.2 [3.7-7.5] times more likely to die prematurely from any cause, and 18.1 [11.5-28.7] times more likely to die by suicide than 15-34 year old females in the general population. Our estimates were 10% and 49% lower, respectively, than previously reported SMRs. Risk of premature mortality was highest in studies with older participants, although confounding by treatment was present. Gender, ascertainment, and diagnostic criteria also impacted risk.

Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa.

CONTEXT: Anorexia nervosa (AN), a prevalent psychiatric disorder predominantly affecting women, is characterized by self-induced starvation and low body weight. Increased clinical fractures are common, and most women have low bone mineral density (BMD). Previously investigated treatments have led to no or modest increases in BMD in AN. OBJECTIVE: Our objective was to investigate the effect of teriparatide (TPT; human PTH[1-34]), an anabolic agent, on low bone mass in women with AN. DESIGN, SETTING, AND PATIENTS: This randomized, placebo-controlled trial at a clinical research center included 21 women with AN: 10 (mean age ± SEM, 47 ± 2.7 years) treated with TPT and 11 (47.1 ± 2.3 years) treated with placebo. INTERVENTIONS: TPT (20 µg s.c.) or placebo was administered for 6 months. MAIN OUTCOME MEASURES: Our primary outcome measure was change in BMD of the spine and hip by dual-energy x-ray absorptiometry. Secondary outcome measures included changes in serum N-terminal propeptide of type 1 procollagen (P1NP), C-terminal collagen cross-links, sclerostin, and IGF-1 levels. RESULTS: At 6 months, spine BMD increased significantly more with TPT (posteroanterior spine, 6.0% ± 1.4%; lateral spine, 10.5% ± 2.5%) compared with placebo (posteroanterior spine, 0.2% ± 0.7%, P < .01; lateral spine, -0.6% ± 1.0%; P < .01). The results remained significant after controlling for baseline body mass index, P1NP, and IGF-1. Changes in femoral neck (P = .4) and total hip (P = 0.8) BMD were comparable in both groups, as were changes in weight. Serum P1NP levels increased after 3 months of TPT treatment and remained at this higher level at 6 months, whereas P1NP levels were unchanged in the placebo group (P = .02). TPT was well-tolerated by all subjects. CONCLUSIONS: This study demonstrates that TPT administration increases spine BMD substantially after only 6 months of therapy in women with AN.

Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa.

OBJECTIVE: Corticotrophin-releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with AN, even after weight recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite and the association with food-motivation neurocircuitry hypoactivation are unknown in AN. We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN. DESIGN: Cross-sectional study of 36 women (13 AN, ten weight-recovered AN (ANWR), and 13 healthy controls (HC)). METHODS: Peripheral cortisol and ACTH levels were measured in a fasting state and 30, 60, and 120 min after a standardized mixed meal. The visual analog scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure the brain activation pre- and post-meal. RESULTS: In each group, serum cortisol levels decreased following the meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs HC. Mean postprandial ACTH levels were high in ANWR compared with HC and AN subjects. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in the food-motivation brain regions (e.g. hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula). CONCLUSIONS: HPA activation may contribute to the maintenance of AN by the suppression of appetitive drive.

A longitudinal investigation of mortality in anorexia nervosa and bulimia nervosa.

OBJECTIVE Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders. METHOD Beginning in 1987, 246 treatment-seeking female patients with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search. RESULTS Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 (95% CI=2.4-7.3) for lifetime anorexia nervosa and 2.33 (95% CI=0.3-8.4) for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among patients with lifetime anorexia nervosa peaked within the first 10 years of follow-up, resulting in a standardized mortality ratio of 7.7 (95% CI=3.7-14.2). The standardized mortality ratio varied by duration of illness and was 3.2 (95% CI=0.9-8.3) for patients with lifetime anorexia nervosa for 0 to 15 years (4/119 died), and 6.6 (95% CI=3.2-12.1) for those with lifetime anorexia nervosa for >15 to 30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse, low body mass index, and poor social adjustment. CONCLUSIONS These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and poor psychosocial functioning raise the risk for mortality in anorexia nervosa.

Binge/purge thoughts in nonsuicidal self-injurious adolescents: an ecological momentary analysis.

OBJECTIVE: Adolescents who self-injure often engage in bingeing/purging (BP). Ecological momentary assessment (EMA) has potential to offer insight into the relationship between self-injury and BP. The aims of this study were to examine the frequency and context of BP using EMA in a sample of nonsuicidal self-injurious (NSSI) adolescents. METHOD: Thirty adolescents with a history of NSSI responded to questions regarding self-destructive thoughts/behaviors using a palm-pilot device. Descriptive analyses compared thought/behavior contexts during reports of BP and NSSI thoughts/behaviors (occurring together vs. individually). RESULTS: BP thoughts were present in 22 (73%) participants, occurring on 32% of the person-days recorded; 59% of these participants actually engaged in BP behavior. Seventy-nine percent of BP thoughts co-occurred with other self-destructive thoughts. Adolescents were more often with friends/peers than alone or with family when having BP thoughts. Worry and pressure precipitated both BP and NSSI thoughts, but perceived criticism and feelings of rejection/hurt were associated more often with BP thoughts than with NSSI thoughts. DISCUSSION: BP thoughts and behaviors were common in this sample, often occurring with other self-destructive thoughts. Future EMA research is needed to address the function of BP symptoms, the contextual variables that increase risk for BP thoughts, and the factors that predict the transition of thoughts into behaviors in adolescents with and without self-injury.

Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa.

OBJECTIVE: Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa and decreased levels in weight-recovered women with anorexia nervosa compared to healthy controls. A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between postprandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. METHOD: We performed a cross-sectional study of 35 women (13 women with active anorexia nervosa, 9 with weight-recovered anorexia nervosa, and 13 healthy controls). Anorexia nervosa was diagnosed according to DSM-IV-TR criteria. Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120 minutes after a standardized mixed meal. The area under the curve (AUC) and, for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). The study was conducted from January 2009 to March 2011. RESULTS: In women with anorexia nervosa, oxytocin AUC and postprandial nadir and peak levels were positively associated with STAI trait and STAI premeal and postmeal state scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, all of the relationships remained significant. After controlling for leptin AUC, most of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of the variance in BDI-II scores. CONCLUSIONS: Abnormal postprandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This link may represent an adaptive response of oxytocin secretion to food-related symptoms of anxiety and depression.

Bone density characteristics and major depressive disorder in adolescents.

OBJECTIVE: Major depressive disorder (MDD) is common during adolescence, a period characterized by rapid bone mineral accrual. MDD has recently been associated with lower bone mineral density (BMD) in adults. Our objective was to determine whether MDD is associated with BMD, bone turnover markers, vitamin D, and gonadal steroids in adolescents. METHODS: Sixty-five adolescents 12 to 18 years of age (32 boys: 16 with MDD and 16 controls; 33 girls: 17 with MDD and 16 controls) were included in a cross-sectional study. BMD and body composition were obtained by dual-energy x-ray absorptiometry. Estradiol, testosterone, 25-hydroxy vitamin D levels, N-terminal propeptide of Type 1 procollagen (a marker of bone formation), and Type I collagen C-telopeptide (a marker of bone resorption) were measured. RESULTS: Boys with MDD had a significantly lower BMD at the hip (mean [standard deviation]=0.99 [0.17] g/cm2 versus 1.04 [0.18] g/cm2, body mass index [BMI] adjusted, p=.005) and femoral neck (0.92 [0.17] g/cm2 versus 0.94 [0.17] g/cm2; BMI adjusted, p=.024) compared with healthy controls after adjusting for BMI. This significant finding was maintained after also adjusting for lean mass and bone age (hip: p=.007; femoral neck: p=.020). In girls, there were no significant differences in BMD between the girls with MDD and the controls after adjusting for BMI (p>.17). CONCLUSIONS: Male adolescents with MDD have a significantly lower BMD as compared with healthy controls after adjusting for body mass and maturity. This association is not observed in girls.

Cortisol secretory parameters in young exercisers in relation to LH secretion and bone parameters.

OBJECTIVE: Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers (AE) from eumenorrhoeic exercisers (EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and nonexercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. DESIGN: Cross-sectional. SUBJECTS: We studied 21 AE, 18 EE and 20 nonexercisers aged 14-21 years (BMI 10th-90th%iles). MEASUREMENTS: Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation (P1NP) and bone resorption (CTX) marker were measured. RESULTS: BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve (AUC) were highest in AE (P = 0.04, 0.007, 0.04 and 0.003) and were associated inversely with fat mass (r = -0.29, -0.28 and -0.35, P = 0.03, 0.04 and 0.007). We observed inverse associations between cortisol and LH AUC (r = -0.36, P = 0.008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1NP in nonexercisers. CONCLUSIONS: Higher cortisol secretion in AE compared with EE and nonexercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol.

Cortical microstructure and estimated bone strength in young amenorrheic athletes, eumenorrheic athletes and non-athletes.

CONTEXT: Lower bone density in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and non-athletes may increase fracture risk during a critical time of bone accrual. Finite element analysis (FEA) is a unique tool to estimate bone strength in vivo, and the contribution of cortical microstructure to bone strength in young athletes is not well understood. OBJECTIVE: We hypothesized that FEA-estimated stiffness and failure load are impaired in AA at the distal radius and tibia compared to EA and non-athletes despite weight-bearing exercise. DESIGN AND SETTING: Cross-sectional study; Clinical Research Center SUBJECTS: 34 female endurance athletes involved in weight-bearing sports (17 AA, 17 EA) and 16 non-athletes (14-21 years) of comparable age, maturity and BMI OUTCOME MEASURES: We used HR-pQCT images to assess cortical microarchitecture and FEA to estimate bone stiffness and failure load. RESULTS: Cortical perimeter, porosity and trabecular area at the weight-bearing tibia were greater in both groups of athletes than non-athletes, whereas the ratio (%) of cortical to total area was lowest in AA. Despite greater cortical porosity in EA, estimated tibial stiffness and failure load was higher than in non-athletes. However, this advantage was lost in AA. At the non-weight-bearing radius, failure load and stiffness were lower in AA than non-athletes. After controlling for lean mass and menarchal age, athletic status accounted for 5-9% of the variability in stiffness and failure load, menarchal age for 8-23%, and lean mass for 12-37%. CONCLUSION: AA have lower FEA-estimated bone strength at the distal radius than non-athletes, and lose the advantage of weight-bearing exercise seen in EA at the distal tibia.

Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa.

CONTEXT: Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. OBJECTIVE: The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). MEASURES: Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. RESULTS: Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula. CONCLUSIONS: Oxytocin may be involved in the pathophysiology of anorexia.

Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls.

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.

Elevated pre-morbid weights in bulimic individuals are usually surpassed post-morbidly: implications for perpetuation of the disorder.

OBJECTIVE: To determine how often patients diagnosed with bulimia nervosa (BN) surpass their highest pre-morbid weight during the course of their disorder. METHOD: The weight histories of individuals with BN were determined using retrospective weight data (Study 1) and combined retrospective/prospective data (Study 2). RESULTS: Retrospective analyses indicated that 59.0% (n = 46) and 61.8% (n = 110), respectively, reported that their highest weight was reached after developing BN. In Study 2, 35.3% of participants superseded their highest pre-enrollment weights during 8 years of follow-up, and 71.6% reached a post-morbid highest weight before remission. Across studies, the primary difference between patients who did and did not reach their highest weight post-morbidly was that those who did had an earlier age of onset and longer duration of BN. DISCUSSION: Findings are discussed in terms of possible links between BN and weight-gain proneness, weight fluctuation across the course of BN, and implications for treating BN.

Clinician reactions to patients with eating disorders: a review of the literature.

OBJECTIVE: The delivery of psychiatric services may be affected by clinicians' negative reactions to treatment-resistant or stigmatized patient groups. Some research has found that clinicians across professional disciplines react negatively to patients with eating disorders, but empirical data related to this topic have not been systematically reviewed. The authors sought to review all published empirical studies of clinician reactions to patients with eating disorders in order to characterize negative reactions to these patients and identify patient or clinical factors associated with negative reactions. METHODS: The authors conducted a comprehensive online search for all published studies of clinician reactions in regard to patients with eating disorders. The reference lists of articles found in the literature search were examined to identify additional studies. RESULTS: Twenty studies, published between 1984 and 2010, were found. Clinician negative reactions in regard to patients with eating disorders typically reflected frustration, hopelessness, lack of competence, and worry. Inexperienced clinicians appeared to hold more negative attitudes toward patients with eating disorders than toward other patient groups, but experienced psychotherapists did not experience strong negative reactions to patients with eating disorders. Medical practitioners consistently reported strong feelings of lack of competence in treating eating disorders. Negative reactions to patients with eating disorders were associated with patients' lack of improvement and personality pathology and with clinicians' stigmatizing beliefs, inexperience, and gender. CONCLUSIONS: Research about the impact of negative clinician attitudes toward patients with eating disorders on psychiatric service delivery, including multivariate analyses using larger samples, comparison groups, validated instruments, and experimental methods, is much needed.