The University of Michigan Depression Center Colloquium Series

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 ColloquiumEating 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 Healthy Eater Typical Dieter Pathological Dieter ED-NOS ED Protective Factors

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 Healthy Eater Typical Dieter Pathological Dieter ED-NOS ED Protective Factors

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 representationsof 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 deathin 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; 5:1119Johnson 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. Adol Onset All Ages Steinhausen HC. Am J Psychiatr 2002; 159:1284

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