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.

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.

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.

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.

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.

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.

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.

Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat.

OBJECTIVE: Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum. DESIGN: Cross-sectional. PATIENTS: 64 women: 15 with AN, 12 normal-weight with HA, 17 overweight or obese (OB) and 20 normal-weight in good health (HC). MEASUREMENTS: Fasting serum leptin and plasma ghrelin levels were measured. Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Perceived Stress Scale were administered. RESULTS: Leptin levels were inversely associated with HAM-D, HAM-A and Perceived Stress scores. The negative relationships between leptin and severity of symptoms of both depression and anxiety remained significant after controlling for body fat or weight. There was no relationship between ghrelin and symptoms of depression or anxiety. Although ghrelin levels were positively associated with the degree of perceived stress, this relationship was not significant after controlling for body fat or weight. CONCLUSIONS: Leptin may mediate depressive symptoms across the weight spectrum. Further investigation of the role of leptin in modulating mood will be important.

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.

An investigation of the joint longitudinal trajectories of low body weight, binge eating, and purging in women with anorexia nervosa and bulimia nervosa.

OBJECTIVES: To describe the longitudinal course of three core eating disorder symptoms-low body weight, binge eating, and purging-in women with anorexia nervosa (AN) and bulimia nervosa (BN) using a novel statistical approach. METHOD: Treatment-seeking women with AN (n = 136) or BN (n = 110) completed the Eating Disorders Longitudinal Interval Follow-Up Evaluation interview every 6 months, yielding weekly eating disorder symptom data for a 5-year period. Semiparametric mixture modeling was used to identify longitudinal trajectories for the three core symptoms. RESULTS: Four individual trajectories were identified for each eating disorder symptom. The number and general shape of the individual trajectories was similar across symptoms, with each model including trajectories depicting stable absence and stable presence of symptoms as well as one or more trajectories depicting the declining presence of symptoms. Unique trajectories were found for low body weight (fluctuating presence) and purging (increasing presence). Conjunction analyses yielded the following joint trajectories: low body weight and binge eating, low body weight and purging, and binge eating and purging. DISCUSSION: The course of individual eating disorder symptoms among patients with AN and BN is highly variable. Future research identifying clinical predictors of trajectory membership may inform treatment and nosological research.

Weight suppression predicts weight change over 5 years in bulimia nervosa.

Recent studies suggest that weight suppression (WS), defined as the discrepancy between current and highest past weight, predicts short-term weight gain in bulimia nervosa (BN) during treatment. The current study was designed to build on this preliminary work by examining the relation between WS and long-term weight change in BN. Treatment-seeking women (N=97) with DSM-IV BN participated in a naturalistic longitudinal follow-up study of eating disorders. At intake, height and weight were measured and highest past weight was assessed. Self-reported weights were collected every 6 months for 5 years. Hierarchical Linear Modeling (HLM) estimated growth curves for weight change over time. Significant inter-person variability was detected for intercepts and slopes (P<0.001) so both were treated as random effects. Participants' weights increased over the study course, moderated by baseline WS (P<0.001), such that higher WS predicted more rapid weight gain. Weight change was not associated with entry weight, height, or highest-ever weight, suggesting that WS per se predicted weight change. These findings complement previous short-term studies in BN by demonstrating that WS predicts weight gain over 5 years. Because weight gain could spur radical dieting that maintains BN, these results have important treatment implications.

Use of SSRIs may Impact Bone Density in Adolescent and Young Women with Anorexia Nervosa.

OBJECTIVES: Alterations in serotonin impact bone metabolism in animal models, and selective serotonin reuptake inhibitors (SSRI) have been associated with increased fracture risk in older adults. SSRIs are commonly used in anorexia nervosa (AN), a condition that predisposes to low bone mineral density (BMD). Our objective was to determine whether SSRI use is associated with low BMD in AN. METHODS: We examined Z-scores for spine, hip and whole body (WB) BMD, spine bone mineral apparent density and WBBMC/height (Ht) in females with AN 12-21 years old who had never been on SSRIs, on SSRIs for <6 months (<6M) or >6 months (>6M). RESULTS: Subjects on SSRIs for >6M had lower spine, femoral-neck and WBBMD Z-scores than those on SSRIs for <6M. Hip BMD and WBBMC/Ht Z-scores were lowest in subjects on SSRIs for >6M. Duration of SSRI use, duration since AN diagnosis and duration of amenorrhea inversely predicted BMD, whereas BMI was a positive predictor. In a regression model, duration of SSRI use remained an independent negative predictor of BMD. DISCUSSION: Duration of SSRI use >6M is associated with low BMD in AN. CONCLUSION: It may be necessary to monitor BMD more rigorously when duration of SSRI use exceeds 6M.

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.

Bone metabolism in adolescent boys with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys. HYPOTHESES: We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers. METHODS: We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12-19 yr old. RESULTS: Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers. CONCLUSION: AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.

Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II.

INTRODUCTION: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Baseline predictors of temporal BMD changes (DeltaBMD) in AN, including 1) gastrointestinal peptides regulating food intake and appetite that have been related to bone metabolism and 2) bone turnover markers, have not been well characterized. We hypothesized that baseline levels of nutritionally regulated hormones and of bone turnover markers would predict DeltaBMD overall. METHODS: In a prospective observational study, lumbar and whole-body BMD was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Baseline body mass index, lean mass, nutritionally regulated hormones [IGF-I, cortisol, ghrelin, leptin, and peptide YY (PYY)], bone formation, and resorption markers were examined to determine nutritional and hormonal predictors of bone density changes. RESULTS: In a regression model, baseline ghrelin and PYY predicted changes in spine bone measures; and baseline ghrelin, cortisol, and PYY predicted changes in whole-body bone measures independent of baseline nutritional status. CONCLUSIONS: Neuroendocrine gastrointestinal-derived peptides regulating food intake are independent predictors of changes in bone mass in AN.

Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1.

CONTEXT: Adolescents with anorexia nervosa (AN) have low bone mineral density. However, the effect of disease recovery, first, on bone density measures assessed using the Molgaard approach, which differentiates between reported low bone density resulting from short bones (based on height Z-scores) and that resulting from thin bones [based on measures of bone area (BA) for height] or light bones [based on measures of bone mineral content (BMC) for BA]; and second, on height-adjusted bone density measures, has not been well characterized. We hypothesized that menstrual recovery and weight gain (> or =10% increase in body mass index) would predict an increase in these measures of bone density. METHODS: In a prospective observational study, lumbar and whole-body (WB) bone density was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Using Ward's modification of the Molgaard approach, we determined measures of BMC for BA and BA for height at the lumbar spine and WB and also determined spine bone mineral apparent density and WB BMC adjusted for height. RESULTS: Girls with AN had lower spine BMC for BA Z-scores (P = 0.0009), and lower WB BA for height Z (P < 0.0001), compared with controls. Menstrual recovery and weight gain in AN (AN-recovered) (median 9 months) resulted in a stabilization of BMD measures, whereas BMD continued to decrease in AN who did not gain weight and recover menses (AN-not recovered). AN-recovered also predicted greater increases in spine BMC for BA and WB BA for height, compared with AN-not recovered (P < 0.05). CONCLUSIONS: Even short-term weight gain with menstrual recovery is associated with a stabilization of BMD measures.

Diagnostic crossover in anorexia nervosa and bulimia nervosa: implications for DSM-V.

OBJECTIVE: The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic "crossover" among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system. METHOD: A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period. RESULTS: Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa. CONCLUSIONS: These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema.

Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a psychiatric illness that results in significant bone loss. Studies examining the neuroendocrine dysregulation that occurs in AN may increase understanding of endocrine systems that regulate bone mass. Peptide YY (PYY) is an anorexigenic peptide derived primarily from the intestine, with actions mediated via activation of Y receptors. We have previously shown that PYY levels are elevated in adolescents with AN. Y2 receptor knockout mice have increased bone mineral density (BMD) and thus PYY may play a role in regulating bone mass. We hypothesized that PYY levels would be inversely associated with BMD in women with AN. METHODS: This was a cross-sectional study performed in a General Clinical Research Center of 12 adult women with AN, (mean+/-SEM) mean age 30.9+/-1.8 years, BMI 17.1+/-0.4 kg/m2, and % ideal body weight 77.5+/-1.7%. PYY concentrations were measured hourly from 20:00 h to 08:00 h. BMD was measured using dual X-ray absorptiometry (DXA). RESULTS: In women with AN, mean overnight PYY levels strongly inversely correlated with BMD at the PA spine (r=-0.77, p=0.003), lateral spine (r=-0.82, p=0.002), total hip (r=-0.75, p=0.005), femoral neck (r=-0.72, p=0.009), total radius (r=-0.72, p=0.009) and 1/3 distal radius (r=-0.81, p=0.002). Body mass index was inversely correlated with PYY level (r=-0.64, p=0.03). Multivariate stepwise regression analysis was performed to determine the contribution of age, duration of AN, BMI, fat-free mass, and PYY to BMD. For PA and lateral spine, PYY was the primary determinant of BMD, accounting for 59% and 67% of the variability, respectively. Fat-free mass and duration of anorexia nervosa were the primary determinants of BMD at other skeletal sites. CONCLUSIONS: In women with anorexia nervosa, an elevated PYY level is strongly associated with diminished BMD, particularly at the spine. Therefore further investigation of the hypothesis that PYY may contribute to the prevalent bone pathology in this disorder is merited.