1. The University of Michigan Depression Center Colloquium Series The Colloquium Series is made possible by an educational grant from GlaxoSmithKline.

2. U-M Depression Center Colloquium Eating Disorders and Depression: Clinical Context David S. Rosen, M.D., M.P.H University of Michigan Medical School Ann Arbor, Michigan, USA

3. Spectrum of Eating Disorders Risk Factors Protective Factors Healthy Eater Typical Dieter Pathological Dieter ED-NOSED

4. Prevalence of Eating Disorders %

5. Anorexia Nervosa: DSM-IV Diagnosis Weight loss (or refusal to gain weight) below normal for age and height Fear of fat, even though underweight Body image distortion; or overconcern about weight or shape even though underweight Amenorrhea (abnormal fxn of H-P-G axis)

6. Anorexia Nervosa: Presentation Nutritional deficiency and wasting Delusion of being fat Obsession to be thinner Denial High rates of medical complications High rates of psychiatric co-morbidity

7. Anorexia Nervosa: Epidemiology Point prevalence < 1% Lifetime prevalence: ~ 0.6-4.0% Increasing prevalence in past 30 years Females >> males Typically presents in adolescence Increasing presentation among “atypical” patients (e.g., males, children, people of color, immigrants, low SES) Partial syndromes are common

8. Bulimia Nervosa: DSM-IV Diagnosis Binge eating; lack of control over binges Abnormal compensatory behavior to manage weight Overconcern with body weight or shape Symptoms at least 2x/week for 3 mo

9. Bulimia Nervosa: Presentation Recurrent, secretive binge eating Awareness that eating is abnormal Fear of loss of control over eating Short-term relief from compensatory behaviors Depression, shame, guilt Low, normal, or high weight High rates of medical complications High rates of psychiatric co-morbidity

10. Bulimia Nervosa: Epidemiology Point prevalence: ~ 0.4-3.0% Lifetime prevalence: ~ 1-6% Increasing prevalence in past 10 years Females >>> males Occurs primarily in older adolescents and young adults Partial syndromes are common

11. Spectrum of Eating Disorders Risk Factors Protective Factors Healthy Eater Typical Dieter Pathological Dieter ED-NOSED

12. Eating Disorders: Etiology Multifactorial Etiology: Biologic risk factors Individual/psychological risk factors Familial risk factors Sociocultural risk factors

13. Etiology: Biologic Risk Factors EDs aggregate within families with distinct and significant genetic effects Genetic (and environmental) influences vary across adolescence and may be variably expressed at different stages of development Consistent association of EDs with alteration in Serotonin function

14. Etiology: Biologic Risk Factors Native animal models of AN exist among swine, sheep, and goats: Genetically determined physiological response to excessive leanness; oversensitivity to stress Animal models of binge eating have been developed in rats: Restriction/re-feeding cycles; response to stress; exposure to highly palatable food. Binge eating appears to be motivated by reward rather than metabolic need

15. Etiology: Heritable Risk AN 11x more likely in female relatives of AN proband vs. relatives of controls BN 4-5x more likely in female relatives of BN proband vs. relatives of controls ~15% lifetime risk of ED in female relatives of AN or BN proband vs. 4% lifetime risk in relatives of controls Strober et al. Am J Psychiatry 2000; 157:393

16. Etiology: Individual Characteristics Perfectionism Over-achieving Obsessional thinking Low self-esteem Depression ? History of sexual abuse

17. Etiology: Sociocultural Pressure Society’s focus on attractiveness Prevailing cultural stereotypes “Thin is beautiful” Unhealthy media representations of women Emergence of “pro-Ana” and “pro-mia” influences

19. Malnutrition Decreased metabolic rate Inability to maintain body temperature Decrease in brain mass (? Reversible) Cognitive changes Affective symptoms Medical sequelae of malnutrition are the leading cause of death in anorexia nervosa

20. Medical Complications of EDs Cardiovascular complications Gastrointestinal complications Fluid/electrolyte complications Skeletal complications Renal complications Endocrine, hormonal, and reproductive complications Skin and dental complications Re-feeding syndrome

21. Psychiatric Co-morbidity Affective disorders, suicidality Anxiety disorders Obsessional behavior, OCD Substance abuse Suicide is the leading cause of death in bulimia nervosa

22. Anxiety Disorders and EDs Methodologically rigorous controlled study of 271 women with AN and BN: Lifetime co-morbidity with at least one anxiety d/o: ~ 70% (significantly > controls) Most anxiety disorders persist after recovery In approximately half of co-morbid cases, the anxiety disorder precedes the ED Godart NT et al. Psychiatr Res 2003; 117:245

23. Depression and EDs Longitudinal, community-based, “Children in the Community” study: Depressive disorders are independent risk factors for the development of EDs (OR=8.45) and ED Sx. Depressive disorders during early adolescence are associated with development of later EDs EDs during adolescence associated with significantly increased risk of depressive (OR=4.32) and anxiety disorders (OR=4.13) during early adulthood. Johnson JG et al. J Consulting and Clin Psychol 2002; 5:1119 Johnson JG et al. Arch Gen Psychiatry 2002; 59:545

24. AN: State-of-the-Art Treatment Few RCTs and little evidence. Interdisciplinary treatment is considered to be the standard of care Early nutritional rehabilitation is essential CBT is the most useful psychotherapy In adolescents, evidence strongly supports family-oriented treatment Limited role for pharmacotherapy

25. BN: State-of-the-Art Treatment Self-help strategies are of limited value BN-focused CBT is the most effective treatment but short-term outcomes are still poor (< 50%) Pharmacotherapy (SSRIs, Topiramate) is a useful adjunct to CBT but is less effective as monotherapy or when combined with self-help Early response to treatment is a useful predictor of both short- and long-term outcomes

26. Prognosis: Inadequate data; inadequate follow-up Variable definitions of “recovery” and “cure” Long-term outcomes are better than previously assumed Significant ongoing risk of psychiatric illness Relapse prevention is important! Mortality is still significant

27. Outcome of AN by Age at Onset and Duration of Follow-up Both younger age at onset, and longer duration of follow-up are associated with better outcomes. Steinhausen HC. Am J Psychiatr 2002; 159:1284 Adol Onset All Ages

28. Prognosis At long-term follow-up, most adolescent patients with ED (~70%) have fully recovered and >80% have normal eating, weight, and menses. However, they will have spent more than 1/3 of their lives in treatment! At long-term follow-up, approximately 10% of patients will have persistent AN, 20% will have BN, and 5% will have died. Steinhausen H-C et al. Eur Child & Adolesc Psych 2003; 12:91-98

29. Outcome of Adolescent-Onset ED in a Longitudinal Cohort of Girls: 982 adolescent girls from a school-based Australian cohort; 14-15 y/o at entry Seven waves over six years Point prevalence of ED 2.4% at age 15-18 Point prevalence of ED 3% at age 20 Prevalence of ED 8.8% across entire study Only 11% of teens with ED still had ED at follow-up However, nearly half had persistent depression and/or anxiety at follow-up Patton GC et al. Eur Child and Adol Psychiatr. 2003; 12 (Suppl 1):I25

30. Summary Eating disorders are common, even though AN and BN are uncommon Biology and genetics are fundamental to the etiology of eating disorders Medical complications of eating disorders may affect every organ system and can be serious or fatal. Significant psychiatric co-morbidity

31. Summary Early treatment of adolescent ED may be associated with a better prognosis With excellent treatment, it is reasonable to expect a good prognosis (but be prepared to work at it for a very long time). More effective treatments for ED are urgently needed and may be informed by a better understanding of their biology