Our Longitudinal Study attempts to answer a question posed by many eating disorder patients and families: “What will I be like in 5, 10 or 20 years?”

Since 1987, we have followed 246 treatment-seeking women with anorexia and bulimia to gain a better understanding of what happens to patients over time. Who gets better and how?

The individuals who entered the study were, on average, 21 years old and had been ill for at least three years. We collect our data by interviewing the women at frequent intervals about their eating behaviors, their physical and emotional health, and their functioning in school, work, and social activities.

What are the Longitudinal Study’s Findings?

This seminal study has generated over 40 published papers about eating disorders. Major findings include the following:
Recovery and Relapse:
• The large majority of the women improve symptomatically over time. Even patients who have been ill for a long time can get better. (1)
• Less than half of patients with anorexia fully recover. (1)
• Although more than half of patients with bulimia recover, nearly one-third relapse. (1)

Mortality:
• Mortality is extraordinarily high; it is 12 times that expected for gender and age. (2) (3) (5)
• The suicide rate is 57 times that expected for gender and age. (1) (3)

Alcohol and Drug Use:
• Alcohol and drug abuse occur commonly in patients with eating disorders; in the longitudinal sample, about 17% of patients have reported substance abuse. (2) (5)
• Coexisting substance abuse is the strongest predictor of premature mortality. (6) (7)

Pregnancy:
• We have followed many of these women through pregnancy. Women with eating disorders who regain their health prior to conception and remain nutritionally stable throughout pregnancy are not more prone to obstetrical problems than those who have never had an eating disorder. However, engaging in abnormal weight control behaviors during pregnancy can increase the risk of complications such as miscarriage, premature delivery, Cesarean delivery, low-birth-weight babies, and postpartum depression. (8)

Depression:
• Depression is common in individuals with eating disorders. The course of the depression is often protracted, and relapse is common. Of the 145 participants in our sample who suffered from major depressive disorder (MDD), 102 (70%) recovered from their depression over the course of the study; but 66 (65%) of these 102 patients subsequently relapsed to MDD. Anorexia nervosa-restricting patients were less likely to recover from MDD than bulimia patients. Better psychological functioning and history of MDD were associated with greater chance of recovery from MDD. (9)

Diagnostic Classification of Eating Disorders:
• Our team is studying how well the current classification, which includes anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified (EDNOS) applies to individuals with abnormal eating patterns. This topic is fundamental to all aspects of eating disorders research.
• The current classification system recognizes two subtypes of anorexia nervosa: the restricting type and the binge eating-purging type. In our research, many women with the restricting type developed the binge eating-purging type over time. (10)
• Among women with bulimia nervosa, those with a history of anorexia nervosa suffered a longer course of illness than those without a history of anorexia nervosa. (11)

Weight Suppression in Bulimia Nervosa:
We are collaborating with investigators at Drexel University in Philadelphia to study patterns of weight loss and regain in individuals with bulimia nervosa. Weight suppression is defined as the difference between a patient's past highest weight and her weight at entry into the study. We found that higher weight suppression predicted more rapid weight gain over the first five years of the study. (12)



What part of the Longitudinal Study is now in progress?


Our 2011 NIMH grant is allowing us to assess how the participants in our study are doing now, 25 years after the launch of the project. Interviews are under way.



What do interviewees say about the experience of participating in the study?


“Your study helped me recognize the importance of taking care of myself. The interviewer was always nonjudgmental – someone to connect with – and this meant the world to me because my disorder had always been a secretive and alienating experience.”

"Your study was the first time I had ever felt good about myself. I could tell the interviewer how I really felt about eating without fear that she would judge me or lead me to believe that my disorder was my own fault. I began to think, 'Wow, I'm not alone.'"


Click to read a letter from one of our Longitudinal Study participants.






Neuroendocrine Studies
For over 20 years, the Harris Center has teamed with the MGH Neuroendocrine Unit (NEU), bridging basic science and clinical science to better understand the biological factors that play a role in anorexia nervosa and to develop interventions to address bone loss and other physical consequences of the disorder. Several studies are identifying effective treatments for conditions that often coexist with anorexia nervosa, such as anxiety and depression.



Assessment and Treatment of Bone Loss in Anorexia Nervosa


A large part of our collaboration with the NEU focuses on the assessment and treatment of bone loss in anorexia in adolescent girls and boys, adult women and men, and postmenopausal women.

Severe bone loss affects 90% of patients (regardless of age or gender), placing them at increased risk for bone fractures throughout their lives. The treatments we are developing for this condition can help slow and even reverse bone loss in individuals with anorexia.



Skeletal Architecture in Healthy Young Woman




Skeletal Architecture in Young Woman with Anorexia Nervosa






Factors that Contribute to Bone Loss in Anorexia


It is believed that bone loss in anorexia nervosa stems in part from a combination of dietary and endocrine factors. When an individual does not take in enough food, the chemical messenger system that helps support normal bone growth and maintenance is disrupted. In order to learn more about these complex mechanisms, the research team has examined a number of hormones.


Estrogen
Long recognized for its impact on the female reproductive system, estrogen helps to build and maintain bone strength. As a consequence, the amenorrhea (absence of menstrual periods) and low estrogen levels that typify anorexia nervosa contribute to bone loss. (13)

Growth Hormone
Growth hormone is secreted by the pituitary gland, a small but crucial structure at the base of the brain. In healthy individuals, growth hormone stimulates bone formation. In anorexia nervosa, growth hormone is high in concentration but impaired in its ability to increase bone formation and therefore bone density. (14)

Testosterone
Although some people think of testosterone as existing only in men, small amounts of this hormone are also produced by women, mostly in the ovaries. Testosterone levels are low in women with anorexia nervosa (as compared to normal controls) and this deficiency is associated with abnormal bone density and fat-free body mass. (15) Interestingly, reduced testosterone levels may also contribute to the anxiety, depression and unhealthy eating behaviors that are characteristic of anorexia nervosa. (16) (17) We are now collaborating with the NEU on a five-year, NIMH-funded study of physiologic testosterone in anorexia nervosa (low-dose testosterone to bring hormone to normal levels).

Hormones Regulated by Nutrition
Hormones that are involved in appetite and eating behavior, such as Insulin-like growth factor-1 (IGF-1), cortisol, ghrelin and Peptide YY (PYY), are likely to influence bone mass. (18) Synthesized by the liver, IGF-1 promotes bone formation; levels of IGF-1 decline with undernutrition in individuals with anorexia nervosa, and are an important cause of low bone density. As a result of insufficient food intake, levels of the stress hormone cortisol increase, further contributing to the problem of bone loss. (19) High cortisol levels are associated with the depression that is often experienced in anorexia nervosa. (20)

Ghrelin and PYY, which help regulate eating behavior and appetite, are higher in concentration in individuals with anorexia nervosa than in healthy controls. Both of these hormones play a role in bone density changes in this disorder. (21) (22) (23) So does leptin, a protein that is found at lower levels in individuals with anorexia nervosa than in normal controls. (24)



Researching New Treatments for Bone Loss in Anorexia


Recent findings suggest that bone density tends to stabilize in adolescent girls with anorexia nervosa who gain weight and resume their menstrual periods in contrast to those who do not gain weight or bring back their menses, in whom bone density continues to drop. (25) (26) Research into effective treatments for anorexia nervosa-induced osteopenia has suggested that IGF-1 and biphosphonates such as risedronate (Actonel) are promising, at least in adults (27) (28). Recently we completed the largest study of estrogen in the treatment of osteoporosis in teenage anorexia nervosa and we are now continuing this investigation using IGF-1. (29) Birth control pills have not been shown to be effective in treating bone loss in this population. (30)

Stigma and Eating Disorders
The Harris Center has been collaborating with Boston University to explore the public’s perception of eating disorders. In a recent study, 173 college students were shown one of three videos describing anorexia as a product of either biology, culture, or an interaction between the two. After watching the videos, the participants completed a questionnaire designed to measure which explanation evoked the least stigmatizing attitudes. Those who viewed the interaction video demonstrated less stigma than those who viewed the sociocultural video but more than those who viewed the biology video. (31)

Harris Center Research Collaborators:

• Neuroendocrine Unit, MGH
• Depression Clinical and Research Program, Department of Psychiatry, MGH
• ADHD Research Program, Department of Psychiatry, MGH
• Adolescent Medicine, MGH
• McLean Hospital
• Harvard University
• University of Chicago
• Drexel University
• Duke University

We thank the National Institute of Mental Health (NIMH), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Alcohol Abuse and Alcoholism (NIAAA), and the National Institute of Drug Abuse (NIDA) for making our research possible.

REFERENCES:
1. Herzog, D.B., Keller, M.B., Sacks, N.R., Yeh, C.J., Lavori, P.W. Recovery and relapse in anorexia and bulimia nervosa: a 7.5-year follow-up study. Journal American Academy Child and Adolescent Psychiatry. 1999; 38: 829-37.

2. Keel, P.K., Dorer, D.J., Eddy, K.T., Franko, D.L., Charatan, D.L., Herzog, D.B. Predictors of mortality in eating disorders. Archives of General Psychiatry. 2003; 60: 179-183.

3. Keel, P.K., Herzog, D.B. Long-term outcome, course of illness and mortality in anorexia nervosa, bulimia nervosa, and binge eating disorder. In: Brewerton, T.D. (Ed.). Clinical Handbook of Eating Disorders: An Integrated Approach. 2004. New York, Marcel Dekker.

4. Franko, D.L., Keel, P.K., Dorer, D., Blais, M., Delinsky, S.S., Eddy, K.T., Charat, V., Renn, R., Herzog, D.B. What predicts suicide in women with eating disorders? Psychological Medicine. 2004; 34: 843-53.

5. Herzog, D.B., Greenwood, D.N., Dorer, D.J., Flores, A.T., Ekeblad, E.R., Richards, A., Blais, M.A. Mortality in eating disorders. International Journal of Eating Disorders. 2000; 28: 20-26.

6. Franko, D.L., Dorer, D.J., Keel, P.K., Jackson, S., Manzo, M.P.,Herzog, D.B. How do eating disorders and alcohol use disorders influence each other? International Journal of Eating Disorders. 2005; 38: 200-207.

7. Herzog, D.B., Franko, D.L., Dorer, D.J., Keel, P.K., Jackson, S., Manzo, M.P. Drug abuse in women with eating disorders. International Journal of Eating Disorders. 2006; 39: 364-368.

8. Franko, D.L., Blais, M.A., Becker, A.E., Delinsky, S.S., Greenwood, D.N., Flores, A.T., Ekeblad, E.R., Eddy, K.T., Herzog, D.B. Pregnancy complications and neonatal outcomes in women with eating disorders. American Journal of Psychiatry. 2001; 158: 1461-6.

9. Mischoulon, D., Eddy, K.T., Keshaviah, A., Dinescu, D., Ross, S., Kass, A., Franko, D.L., Herzog, DB. Depression and Eating Disorders: Treatment and Course. Journal of Affective Disorders. (In press).

10. Eddy, K.T., Dorer, D.J., Franko, D.L., Tahilani, K., Thompson-Brenner, H., Herzog, D.B. Diagnostic crossover in anorexia nervosa and bulimia nervosa: implications for DSM-V. American Journal of Psychiatry. 2008; 165:245-250.

11. Eddy, K.T., Dorer, D.J., Franko, D.L., Tahilani, K., Thompson-Brenner, H., Herzog, D.B. Should bulimia nervosa be subtyped by history of anorexia nervosa? A longitudinal validation. International Journal of Eating Disorders. 2007; 40: S67-S71.

12. Herzog, D.B., Thomas, J.G., Kass, A.E., Eddy, K.T., Franko, D.L., Lowe, M.R. Weight suppression predicts weight change over 5 years in bulimia nervosa. Psychiatry Research. 2010; 177: 330-4.

13. Soyka, L.A., Grinspoon, S., Levitsky, L.L., Herzog, D.B., Klibanski, A. The effects of anorexia nervosa on bone metabolism in female adolescents. Journal of Clinical Endocrinology & Metabolism. 1999; 84: 4489-96.

14. Misra, M., Miller, K.K., Bjornson, J., Hackman, A., Aggarwal, A., Chung, J., Ott, M., Herzog, D.B., Johnson, M.L., Klibanski, A. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. Journal of Clinical Endocrinology & Metabolism. 2003; 88: 5615-23.

15. Miller, K.K., Lawson, E.A., Mathur, V., Wexler, T.L., Meenaghan, E., Misra, M., Herzog, D.B., Klibanski, A. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. Journal of Clinical Endocrinology & Metabolism. 2007; 92:1334-9.

16. Miller, K.K., Deckersbach, T., Rauch, S.L., Fischman, A.J, Grieco, K.A., Herzog, D.B., Klibanski, A. Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa. Psychiatry Research. 2004; 132:197-207.

17. Miller, K.K., Wexler, T.L., Zha, A.M., Lawson, E.A., Meenaghan, E.M., Misra, M., Binstock, A.B., Herzog, D.B., Klibanski, A. Androgen deficiency: association with increased anxiety and depression symptom severity in anorexia nervosa. Journal of Clinical Psychiatry. 2007; 68: 959-65.

18. Misra, M., Prabhakaran, R., Miller, K.K., Goldstein, M.A., Mickley, D., Lockhart, P., Cord, J., Herzog, D.B., Katzman, D.K., Klibanski, A. Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II. Journal of Clinical Endocrinology & Metabolism. 2008; 93: 1292-7.

19. Misra, M., Miller, K.K., Almazan, C., Ramaswamy, K., Lapcharoensap, W., Worley, M., Neubauer, G., Herzog, D.B., Klibanski, A. Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. Journal of Clinical Endocrinology & Metabolism. 2004; 89: 4972-4980.

20. Lawson, E.A., Donoho, D., Miller, K.K., Misra, M., Meenaghan, E., Lydecker, J., Wexler, T., Herzog, D.B., Klibanski, A. Hypercortisolemia is associated with severity of bone loss and depression in hypothalamic amenorrhea and anorexia nervosa. Journal of Clinical Endocrinolology & Metabolism. 2009; 94: 4710-6.

21. Misra, M., Miller, K.K., Kuo, K., Griffin, K., Stewart, V., Hunter, E., Herzog, D.B., Klibanski, A. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. American Journal of Physiology-Endocrinology and Metabolism. 2005; 289: E347-56.

22. Misra, M., Miller, K.K., Tsai, P., Gallagher, K., Lin, A., Lee, N., Herzog, D.B., Klibanski, A. Elevated peptide YY levels in adolescent girls with anorexia nervosa. Journal of Clinical Endocrinology & Metabolism. 2006; 91:1027–1033.

23. Russell M, Stark J, Nayak S, Miller KK, Herzog DB, Klibanski A, Misra M. Peptide YY in adolescent athletes with amenorrhea, eumenorrheic athletes and non-athletic controls. Bone. 2009; 45: 104-9.

24. Misra, M., Miller, K.K., Kuo, K., Griffin, K., Stewart, V., Hunter, E., Herzog, D.B., Klibanski, A. Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents. American Journal of Physiology-Endocrinology and Metabolism. 2005; 289: E373-81.

25. Misra, M., Prabhakaran, R., Miller, K.K., Goldstein, M.A., Mickley, D., Clauss, L., Lockhart, P., Cord, J., Herzog, D.B., Katzman, D.K., Klibanski, A. Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1. Journal of Clinical Endocrinology & Metabolism. 2008; 93: 1231-7.

26. Miller, K.K., Lee, E.E., Lawson, E.A., Misra, M., Minihan, J, Grinspoon, S.K., Gleysteen, S., Mickley, D., Herzog, D.B., Klibanski, A. Determinants of skeletal loss and recovery in anorexia nervosa. Journal of Clinical Endocrinology & Metabolism. 2006; 91: 2931-7.

27. Grinspoon, S., Miller, K., Herzog, D., Clemmons, D., Klibanski, A. Effects of recombinant human insulin-like growth factor (IGF)-I and estrogen administration on IGF-I, IGF binding protein (IGFBP)-2, and IGFBP-3 in anorexia nervosa: a randomized-controlled study. Journal of Clinical Endocrinology & Metabolism. 2003; 88: 1142-1149.

28. Miller, K.K., Grieco K.A., Mulder, J., Grinspoon, S., Mickley, D., Yehezkel, R., Herzog, D.B., Klibanski, A. Effects of risedronate on bone density in anorexia nervosa. Journal of Clinical Endocrinology & Metabolism. 2004; 89: 3903-6.

29. Misra, M., Katzman, D.K., Miller, K.K., Mendes, N., Snelgrove, D., Russell, M., Goldstein, M.A., Ebrahimi, S., Clauss, L., Weigel, T., Mickley, D., Schoenfeld, D., Herzog, D.B., Klibanski, A. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. Journal of Bone and Mineral Research. (In press).

30. Klibanski, A., Biller, B.M.K., Schoenfeld, D.A., Herzog, D.B., Saxe, V.C. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. Journal of Clinical Endocrinology & Metabolism. 1995; 80: 898-904.

31. Crisafulli, M.A., Thompson-Brenner, H., Franko, D.L., Eddy, K.T., Herzog, D.B. Stigmatization of anorexia nervosa: Characteristics and response to intervention. Journal of Social and Clinical Psychology. 2010; 29: 756-770.


Photo Credits
Manuscript 1
Manuscript 2
Manuscript 3
Manuscript 4
Manuscript 5
Manuscript 6
Manuscript 7
Technician transfering liquid to test tube
Skeletal Architectures: Courtesy of Massachusetts General Hospital Neuroendocrine Unit
Beakers in a lab
Human Brain
Oklahoma Army National Guard, 120th Med. Co.
Manuscript 8

This page was updated on June 30, 2011.