David B. Herzog’s research while affiliated with Harvard Medical School and other places

Longitudinal associations between eating disorders (EDs) and comorbid psychiatric disorders are poorly understood but important to examine as comorbidities are common and can impede ED recovery. We examined two common comorbidities, major depressive disorder (MDD)and substance use disorder (SUD), in adult women with intake diagnoses of anorexia nervosa(AN) and bulimia nervosa (BN) who participated in a longitudinal study. To test the longitudinal reciprocal relations among ED, MDD, and SUD, we conducted a multi-group autoregressive cross-lagged path analysis. We tested whether ED, MDD, and SUD in a given three-month period (t — 1)each predicted ED, MDD, and SUD during the subsequent three-month period (t) over 5 years. We examined the moderating effect of intake diagnosis (AN vs. BN). Among AN (but not BN)participants, having MDD at t — 1 predicted having an ED at time t, OR = 1.98, B = .68, z = 2.49,p = .01. Among BN (but not AN) participants, having a SUD at t — 1 predicted having an ED at time t, OR = 5.16, B = 1.64, z = 2.34, p = .01. In contrast, having an ED at t — 1 did not predict MDD or SUD at time t for AN or BN participants. These results suggest for individuals with AN and MDD, treating MDD may facilitate ED recovery. For individuals with BN and SUD, treating SUD may facilitate ED recovery. These identified temporal associations between ED and comorbid disorders may guide cognitive behavioral researchers and therapists in prioritizing treatment targets given the high rate of comorbidity in EDs.

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.

Context: Anorexia nervosa (AN) is a psychiatric illness with significant 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: 90 women, 18-45 years, with AN and free testosterone levels below the median for healthy women. Intervention: Transdermal testosterone, 300 mcg daily, or placebo patch for 24 weeks. Main outcome measures: Primary endpoint: BMI. Secondary endpoints: 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 to placebo. Conclusions: 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 to placebo in women with AN.

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.

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.

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 (β = 0.43, p < 0.01) and were predicted by intake diagnosis of AN-restricting (β = 0.31, p < 0.01) or AN-binge eating/purging (β = 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.

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.