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The Biological Basis of Bulimia Nervosa
Bulimia nervosa is a serious illness affecting both mind and body. The majority of bulimia nervosa sufferers are adolescent and young adult women. The American Psychiatric Association estimates a lifetime prevalence for bulimia ranging from 1% for narrowly defined criteria to 4.2% for broader definitions of the illness (1). Individuals with bulimia overvalue thinness and rate their self-worth based on the size and shape of their bodies. Features include recurrent episodes of binge eating and inappropriate compensatory behaviors to prevent weight gain such as self-induced vomiting; misuse of laxatives, diuretics or other medications; fasting; or over-exercise (1). Approximately 30% of women with bulimia nervosa have had anorexia nervosa at some point in their lives (2).
Bulimia nervosa is a disorder of the brain. It is widely acknowledged that alterations in central nervous system pathways contribute to the illness. Bulimia sufferers have disturbances in brain serotonin, a neurotransmitter that helps regulate feeding, mood, and neuroendocrine activity (3). Interestingly, patients exhibit serotonin abnormalities not only while they are ill but also after they have stopped bingeing and purging (3). Testing for serotonin after recovery helps determine whether there are remaining deficits in brain function. Abnormalities that persist after recovery suggest that they may have existed prior to the onset of the illness. It is now believed that serotonin imbalances contribute to the long-term mood disturbances, obsessionality and perfectionism seen in individuals with bulimia (3).
Recent research has also focused on a number of neuropeptides (molecular messengers) that act on brain cells to regulate appetite and energy release (4). For example, the peptide hormone ghrelin stimulates hunger signals. Testing for ghrelin before meals reveals higher levels in patients with bulimia than in healthy controls; and after meals, individuals with bulimia show less ghrelin suppression as compared to controls (5, 6). Peptide YY derives from the gastrointestinal tract and tends to decrease food intake. Patients with bulimia demonstrate a diminished PYY response to meals as compared to healthy controls (5, 6). Another neuropeptide that helps reduce appetite is cholecystokinin, which is released by the small intestine; after meals, cholecystokinin concentration is lower in individuals with bulimia than in those without the illness (4, 7). A growing body of evidence points to changes in neuropeptide activity as involved in the disturbed eating and hormone abnormalities that characterize bulimia nervosa.
Family studies have been instrumental in teaching us about the genetic aspects of eating disorders. Results show that bulimia nervosa runs in families (2). Relatives of individuals with bulimia nervosa are at higher risk than relatives of healthy control subjects for full-fledged bulimia nervosa (8) and for less severe forms of the disorder (8, 9). It is not unusual to find anorexia nervosa in the families of patients with bulimia and vice versa (8, 9). Twin studies shed further light on the genetics of bulimia nervosa. Identical twins of individuals with anorexia or bulimia are more likely to develop these illnesses than twin siblings of healthy control subjects (1); and identical twins show higher concordance than fraternal twins (1,10,11).
Bulimia nervosa is polygenic, meaning that its development is influenced not by a single gene but by the combined effects of many. Over the past dozen years, increasing attention has focused on finding the contributing genes. In order to appreciate the complexity of this challenge, it is helpful to think of the human genome (the entirety of a person’s DNA) as a code of over 3 billion molecular bases across 23 pair of chromosomes (12). Genetic makeup is largely determined by the order in which these bases occur. This sequence is very much the same from one person to another, but there are millions of individual differences along the way that can serve as potential identifiers of disease vulnerability (12). Although scientists have not yet located the specific genes that increase the risk of eating disorders, they are making progress. Research conducted about five years ago pointed to significant genetic activity on chromosome 10 p for bulimia nervosa (13), laying the groundwork for important studies that are now underway (14, 15).
Bulimia often co-exists with other polygenic, biologically-based mental illnesses. There is a strong association between bulimia nervosa and affective illness, which in most cases precedes the eating disorder (16). For example, it is quite common for a patient with bulimia to also suffer from major depression (16,17). Obsessive-compulsive symptoms often accompany bulimia and generally persist after recovery from the eating disorder (18,19).
To put the question of biological basis in perspective, it is helpful to note what has been reported about the mental illnesses that often accompany eating disorders. Studies of major depression have yielded valuable clues—particularly about neurotransmitter systems—and called attention to several genes as potential contributors to the illness; yet understanding of the neurochemical and genetic underpinnings of major depression is incomplete (20). Serotonin abnormalities have also been implicated in the biology of obsessive compulsive disorder, and though research to identify the specific genes that confer vulnerability to this condition has moved forward, there is still a long way to go (21).
Additional perspective on the biological basis of eating disorders comes from estimated heritability statistics. Published studies estimate bulimia nervosa’s heritability at about 60% (11, 13, 22-26), which is higher than that of major depression and higher than that of obsessive-compulsive behavior, estimated to be 38% (27) and 36% (28) respectively.
Bulimia nervosa can result in serious medical complications. Vomiting and misuse of laxatives can lead to dehydration and electrolyte imbalances causing the patient to become weak and irritable (1). The most widespread electrolyte abnormality in bulimia nervosa is hypokalemia, a low level of serum potassium, which can potentiate dangerous cardiac arrhythmias and must be treated (29). Although hypokalemia and other electrolyte abnormalities, including low serum sodium (which can cause seizures) are very worrisome in bulimic patients who are underweight (29, 30), they are not the only ones at risk. Normal-weight individuals with bulimia, especially those who purge frequently, are also prone to such imbalances, underscoring the importance of diligent medical monitoring for all who suffer from bulimia nervosa (31).
Some patients with bulimia nervosa use Ipecac, a medication that induces vomiting. The main ingredient of this medication is toxic and its effects build up in the body. Chronic use of Ipecac places individuals with bulimia at risk for muscle weakness, cardiac problems and precipitous death (29, 32).
Complications of the mouth and throat include dental cavities, and erosion of dental enamel due to gastric acid (29). Ten to thirty percent of individuals with bulimia develop enlarged parotid and salivary glands, and this problem resolves when patients receive treatment for their behavioral symptoms (29,33). Abdominal pain, gastro-esophageal reflux, esophagitis, and gastritis (1) are not unusual. Vomitus spotted with blood can be reflective of a small esophageal tear (29); esophageal rupture is rare but very serious, typically resulting in death (29).
With professional treatment, the vast majority of individuals with bulimia improve and many recover (34, 35). A multidisciplinary, team approach to treatment is most effective due to the disease’s complex combination of genetic, neurochemical, psychological and sociocultural factors. Although outpatient care is appropriate for most patients with bulimia, hospitalization is necessary for those with severe electrolyte disturbances, vital sign instability, blood-streaked emesis, suicidality or other acute psychiatric comorbidity (1). Recommended services for individuals with bulimia nervosa generally include monitoring by a primary care physician; laboratory testing; nutrition counseling; individual, group, and/or family therapy, and medication.
One of the most exciting developments in the quest for successful treatment involves the role of antidepressant medication. Numerous clinical trials have revealed that these drugs help patients cut down on bingeing and vomiting episodes (29, 36, 37). Also encouraging is evidence that antidepressants help relieve the mood problems and anxiety that often accompany bulimia (1). The class of antidepressant known as Selective Serotonin Reuptake Inhibitors (SSRIs) includes the well-known Prozac (fluoxetine) as well as similar medications that help regulate neurotransmitter activity in the brain. In 1998, the U.S. Food and Drug Administration approved Prozac for the treatment of bulimia nervosa (37). The SSRIs are usually well tolerated and result in fewer side effects than the older generations of antidepressants (37).
Although clinicians and patients have long believed that psychotherapy is critical to the recovery process, there is now a growing body of scientific evidence to support these claims. Clinical trials indicate that patients treated with cognitive behavioral therapy (CBT) show more improvement than control subjects (38). Based on large samples of patients who receive CBT, the decrease in bingeing and purging is generally 80% or higher (29). CBT teaches patients to restructure negative thoughts into positive ones and leads to improved self-esteem. Many individuals with bulimia do well on a treatment program that combines antidepressants and cognitive behavioral therapy (1,39,40).
Though CBT is time-limited, goal-directed and problem-focused (29), an adequate and effective trial requires more than the number of sessions covered by health insurance companies (41,42). A study conducted in 2000 with a national database indicated that the number of days of care insurance companies cover for an eating disorder falls below the clinically recommended standard (43). In fact, it is not unusual for a practitioner to be making progress with a patient only to learn that the health insurance company is denying payment for further care (44).Well-coordinated, comprehensive treatment programs go a long way in restoring the health of individuals with bulimia nervosa and in preventing relapse of this painful and pernicious illness.
Click to view:
The Biological Basis of Anorexia Nervosa
The Biological Basis of Eating Disorder Not Otherwise Specified (EDNOS)
References: The Biological Basis of Bulimia Nervosa
1. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Eating Disorders, Third Edition. American Journal of Psychiatry. 2006; 163: 4-54.
2. Keel, P.K. Eating Disorders. Upper Saddle River, N.J.: Prentice Hall; 2005.
3. Kaye, W. Neurobiology of anorexia and bulimia nervosa. Physiology and Behavior.
2007 November 29, [Epub ahead of print].
4. Jimerson, D.D., Wolfe, B.E. Neuropeptides in eating disorders. CNS Spectrums. 2004; 9: 516-22.
5. Kojima, S., Nakahara, T., Nagai, N., Muranaga, T., Tanaka, M., Yasuhara, D.,
Masuda, A., Date, Y., Ueno, H., Nakazato, M., Naruo, T. Altered ghrelin and peptide YY responses to meals in bulimia nervosa. Clinical Endocrinology. 2005; 62: 74-8.
6. Monteleone, P., Martiadis, V., Rigamonti, A.E., Fabrazzo, M., Giordani, C., Muller, E.E., Maj, M. Investigation of peptide YY and ghrelin responses to a test meal in bulimia nervosa. Biological Psychiatry. 2005; 57: 926-31.
7. Keel, P.K., Wolfe, B.E., Liddle, R.A., De Young, K.P., Jimerson, D.C.
Clinical features and physiological response to a test meal in purging disorder and bulimia nervosa. Archives of General Psychiatry. 2007; 64: 1058-66.
8. Strober, M., Freeman, R., Lampert, C., Diamond, J., Kaye, W. Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes. American Journal of Psychiatry. 2000; 157: 393–401.
9. Lilenfeld, L.R., Kaye, W.H., Greeno, C.G., Merikangas, K.R., Plotnicov, K., Pollice, C., Rao, R., Strober, M., Bulik, C.M., Nagy, L. A controlled family study of anorexia nervosa and bulimia nervosa: psychiatric disorders in first-degree relatives and effect of proband comorbidity. Archives of General Psychiatry.1998; 55: 603-10.
10. Bulik, C., Sullivan, P.F., Wade, T., Kendler, K. Twin studies of eating disorders: a review. International Journal of Eating Disorders. 2000; 27: 1–20.
11. Kendler, K.S., MacLean, C., Neale, M.C., Kessler, R.C., Heath, A.C., Eaves, L.J. The genetic epidemiology of bulimia nervosa. American Journal of Psychiatry. 1991; 148:1627–1637.
12. “The New Frontiers of Medicine: Cutting-Edge Research in the Fight against Disease.” Harvard Medical School, 2006.
13. Bulik, C.M., Devlin, B., Bacanu, S.A., Thornton, L., Klump, K.L., Fichter, M.M., Halmi, K.A., Kaplan, A.S., Strober, M., Woodside, D.B., Bergen, A.W., Ganjei, J.K., Crow, S., Mitchell, J., Rotondo, A., Mauri, M., Cassano, G., Keel, P., Berrettini, W.H., Kaye, W.H. Significant linkage on chromosome 10p in families with bulimia nervosa. American Journal of Human Genetics. 2003; 72: 200-7.
14. Ando, T., Komaki, G., Naruo, T., Okabe, K., Takii, M., Kawai, K., Konjiki, F., Takei, M., Oka, T., Takeuchi, K., Masuda, A., Ozaki, N., Suematsu, H., Denda, K., Kurokawa, N., Itakura, K., Yamaguchi, C., Kono, M., Suzuki, T., Nakai, Y., Nishizono-Maher, A., Koide, M., Murakami, K., Nagamine, K., Tomita, Y., Ookuma, K., Tomita, K., Tonai, E., Ooshima, A., Ishikawa, T., Ichimaru, Y. Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics . 2006; 141: 929-34.
15. Kaplan, A.S., Levitan, R.D., Yilmaz, Z., Davis, C., Tharmalingam, S., Kennedy, J.L. A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa. International Journal of Eating Disorders. 2008; 41: 22-8.
16. Brewerton, T.D., Lydiard, R.B., Herzog, D.B., Brotman, A.W., O’Neil, P.M., Ballenger, J.C. Comorbidity of axis I psychiatric disorders in bulimia nervosa. Journal of Clinical Psychiatry. 1995; 56:77-80.
17. Herzog, D.B., Keller, M.B., Sacks, N.R., Yeh, C.J., Lavori, P.W. Psychiatric comorbidity in treatment-seeking anorexics and bulimics. Journal of the American Academy of Child and Adolescent Psychiatry. 1992; 31: 810-8.
18. Anderluh M.B., Tchanturia, K., Rabe-Hesketh, S., Treasure, J. Childhood obsessive- compulsive personality traits in adult women with eating disorders: defining a broader eating disorder phenotype. American Journal of Psychiatry. 2003; 160: 242- 7.
19. Von Ranson, K.M., Kaye, W.H., Weltzin, T.E., Rao, R., Matsunaga, H. Obsessive- compulsive disorder symptoms before and after recovery from bulimia nervosa. American Journal of Psychiatry. 1999 ; 156: 1703-8.
20. Barton, D.A., Esler, M.D., Dawood, T., Lambert, E.A., Haikerwal, D., Brenchley, C., Socratous, F., Hastings, J., Guo, L., Wiesner, G., Kaye, D.M., Bayles, R., Schlaich, M.P., Lambert, G.W. Elevated brain serotonin turnover inpatients with depression: effect of genotype and therapy. Archives of General Psychiatry. 2008; 65: 38-46.
21. Saiz, P.A., Garcia-Portilla, M.P., Arango, C., Morales, B., Bascaran, M.T., Martinez- Barrondo, S., Florez, G., Sotomayor, E., Paredes, B., Alvarez, C., San Narciso, G., Carreño, E., Bombin, I., Alvarez, V., Coto, E., Fernandez, J.M., Bousoño, M., Bobes, J. Association study between obsessive-compulsive disorder and serotonergic candidate genes. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2008; 32: 765-770.
22. Kortegaard, L.S., Hoerder, K., Joergensen, J., Gillberg, C., Kyvik, K.O. A preliminary population-based twin study of self-reported eating disorder.
Psychological Medicine. 2001; 31: 361-5.
23. Wade, T., Neale, M.C., Lake, R.I., Martin, N.G. A genetic analysis of the eating and attitudes associated with bulimia nervosa: dealing with the problem of ascertainment in twin studies. Psychological Medicine. 1999; 29: 1-10.
24. Wade, T., Martin, N.G., Neale, M.C., Tiggemann, M., Treloar, S.A., Bucholz, K.K., Madden, P.A., Heath, A.C. The structure of genetic and environmental risk factors for three measures of disordered eating characteristic of bulimia nervosa. Psychological Medicine. 1999; 29: 925-34.
25. Sullivan, P.F., Bulik, C.M., Kendler, K.S. Genetic epidemiology of binging and vomiting. British Journal of Psychiatry. 1998; 173: 75-9.
26. Bulik, C.M., Sullivan, P.F., Kendler, K.S. Heritability of binge-eating and broadly defined bulimia nervosa. Biological Psychiatry. 1998; 44: 1210–1218.
27. Kendler, K.S., Gatz, M. Gardner, C.O., Pedersen, N.L. A Swedish national twin study of lifetime major depression. American Journal of Psychiatry. 2006; 163: 109-14.
28. van Grootheest, D.S., Boomsma, D.I., Hettema, J.M., Kendler, K.S. Heritability of obsessive-compulsive symptom dimensions. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2007 Dec. 14 [epub ahead of print].
29. Commission on Adolescent Eating Disorders. Eating Disorders. In: Evans, D.E., Foa, E.B., Gur, R.E., Hendin, H., O’Brien, C.P., Seligman, M.E.P., Walsh, B.T. (Eds.) Treating and Preventing Adolescent Mental Health Disorders: What We Know and What We Don’t Know; A Research Agenda for Improving the Mental health of Our Youth. New York (NY). Oxford University Press; 2005. p. 258-81.
30. Beumont, P.J., Kopec-Schrader, E.M., Lennerts, W. Eating disorder patients at a NSW teaching hospital: a comparison of state-wide data. The Australian and New Zealand Journal of Psychiatry. 1995; 29: 96-103.
31. Wolfe, B.E., Metzger, E.D., Levine, J.M., Jimerson, D.C. Laboratory screening for electrolyte abnormalities and anemia in bulimia nervosa: a controlled study. International Journal of Eating Disorders. 2001; 30: 288-93.
32. Schiff, R.J., Wurzel, C.L., Brunson, S.C., Kasloff, I., Nussbaum, M.P, Frank, S.D. Death due to chronic syrup of ipecac use in a patient with bulimia. Pediatrics. 1986; 78: 412-6.
33. Mandel, L., Abai, S. Diagnosing bulimia nervosa with parotid gland swelling. Journal of the American Dental Association. 2004; 135: 613-616.
34. Herzog, D.B., Dorer, D.J., Keel, P.K., Selwyn, S.E., Ekeblad, E.R., Flores, A.T., Greenwood, D.N., Burwell, R.A., Keller, M.B. Recovery and relapse in anorexia and bulimia nervosa: a 7.5 year follow-up study. Journal of the American Academy of Child & Adolescent Psychiatry. 1999; 38: 829-37.
35. Fairburn, C.G., Cooper, Z., Doll, H.A., Norman, P., O’Connor, M. The natural course of bulimia nervosa and binge eating disorder in young women. Archives of General Psychiatry. 2000; 57: 659-65.
36. Agras, W.S. Pharmacotherapy of bulimia nervosa and binge eating disorder: longer term outcomes. Psychopharmacology Bulletin. 1997; 33: 433-6.
37. Zhu, A.J., Walsh, B.T. Pharmacologic treatment of eating disorders. Canadian Journal of Psychiatry. 2002; 47: 227-34.
38. National Collaborating Centre for Mental Health: Eating Disorders: Core Interventions in the Treatment and Management of Anorexia Nervosa, Bulimia Nervosa, and Related Eating Disorders. London, National Institute for Clinical Excellence, 2004.
39. Walsh, B.T., Wilson, G.T., Loeb, K.L., Devlin, M.J., Pike, K.M., Roose, S.P., Fleiss, J., Waternaux, C. Medication and psychotherapy in the treatment of bulimia nervosa. American Journal of Psychiatry. 1997; 154: 523-31.
40. Fichter, M.M., Krüger, R., Rief, W., Holland, R., Döhne, J. Fluvoxamine in prevention of relapse in bulimia nervosa: effects on eating-specific psychopathology. Journal of Clinical Psychopharmacology. 1996; 16: 9-18.
41. Rome, E.S., Ammerman, S., Rosen, D.S., Keller, R.J., Lock, J., Mammel, K.A. ,O’Toole, J., Rees, J.M., Sanders, M.J., Sawyer, S.M., Schneider, M., Sigel, E., Silber, T.J. Children and adolescents with eating disorders: the state of the art. Pediatrics. 2003; 111: e98-e108.
42. Franko, D.L., Erb, J. Managed care or mangled care? Treating eating disorders in the current healthcare climate. Psychotherapy. 1998; 35: 43-53.
43. Striegel-Moore, R.H., Leslie, D., Petrill, S.A., Garvin, V., Rosenheck, R.A. One-year use and cost of inpatient and outpatient services among female and male patients with an eating disorder: evidence from a national database of health insurance claims. International Journal of Eating Disorders. 2000; 27: 381-9.
44. Silber,T.J., Robb, A.S. Eating disorders and health insurance understanding and overcoming obstacles to treatment. Child and Adolescent Psychiatric Clinics of North America. 2002; 11: 419-28.
This page was posted on May 14, 2008.
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