Case Analysis – Collaborating with Outside Providers

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A critique of the literature on etiology of eating disorders

Azadeh A Rikani,1,3 Zia Choudhry,1,2,4 Adnan M Choudhry,4 Huma Ikram,5 Muhammad W Asghar,6 Dilkash Kajal,7 Abdul Waheed,8 Nusrat J Mobassarah9

1Douglas Hospital Research Centre, Montreal, Quebec, Canada, H4H 1R3; 2Department of Human Genetics, McGill University, Montreal, Quebec, Canada, H3H 1B1; 3Department of Psychiatry, McGill University, Montreal, Quebec, Canada, H3A 1A1; 4Division of Research & Medical Education, International Maternal and Child Health Foundation, Montreal, QC, Canada, H7S 2N5; 5Neurochemistry Research Unit, University of Karachi, Karachi, Pakistan, 71000; 6Department of Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2E1; 7Department of Medical Imaging, University of Ottawa, Ottawa, ON, K1N 6N5; 8Department of Family and Community Medicine, Pennsylvania State University, Hershey, PA, USA, 17033; 9Institute of Integrated Cell-Material Science, Kyoto University, Yoshida Ushinomiyacho, Sakyo – ku, JAPAN, 606-8501

AbstRACt

The development of eating disorders including anorexia nervosa, bulimia nervosa, binge eating disorder, and atypical eating disorders that affect many young women and even men in the productive period of their lives is complex and varied. While numbers of presumed risk factors contributing to the development of eating disorders are increasing, previous evidence for biological, psychological, developmental, and sociocultural effects on the development of eating disorders have not been conclusive. Despite the fact that a huge body of research has carefully examined the possible risk factors associated with the eating disorders, they have failed not only to uncover the exact etiology of eating disorders, but also to understand the interaction between different causes of eating disorders. This failure may be due complexities of eating disorders, limitations of the studies or combination of two factors. In this review, some risk factors including biological, psychological, developmental, and sociocultural are discussed.

KEYWORDS: Etiology, anorexia nervosa, Bulimia nervosa, Co-morbidity, Binge eating disorder

Corresponding Author: Nusrat J Mobassarah, Ph.D., Institute of Integrated Cell-Material Science, Kyoto University, Yoshida Ushinomiyacho, Sakyo – ku, Japan, 606-8501, Tel.: 81-80-757539869, Fax: 81-80-757539820, E-mail: [email protected]

doi : 10.5214/ans.0972.7531.200409

Introduction

Eating disorders, particularly, anorexia nervosa and bulimia nervosa have been center of attention for clinicians and re- searchers. Eating disorders are one of the significant problems in the care of adoles- cents and even children. These complex disorders are believed to arise from in- teraction of multiple risk factors. Eating disorders are defined by disturbance in eating habits that may be either excessive or insufficient food intake. Bulimia nervo- sa, anorexia nervosa, and binge eating are the most common forms of eating disorder based on diagnostic and statistical manual of mental disorders (DSM-IV). As defined in DSM-IV, anorexia nervosa is a constant attempt to maintain body weight below minimally normal weight (85%) or body mass index <17.5 for age and height, with an intense fear of weight gain even though under weight, and inaccurate perception of own body size, shape, or weight. It may accompany with amenor- rhea in girls and women after menarche. DSM-IV also defines bulimia nervosa as recurrent binge eating episodes followed by recurrent purging, excessive exercise, or prolonged fasting at least two times per week for three months. Excessive concern about weight or shape is also very com- mon in bulimia nervosa. Another type of eating disorders is binge-eating disorder that is characterized with recurrent binge eating without purging, excessive exer-

cise, or fasting. Atypical eating disorder is referred to clinically significant eating disorders associated with unexplained weight loss, rumination, unexplained food intolerances or an extremely picky eating habit that does not meet the criteria of an- orexia nervosa, bulimia, or binge disorder.1

Prevalence of Eating Disorders

The average prevalence rates for anorexia nervosa and bulimia nervosa are 0.3% and 1% among adolescence and young people in western countries respectively. Prevalence rates of anorexia nervosa and bulimia nervosa increase during transition period from adolescence to adulthood.2 Lifetime prevalence rates for eating disor- der are higher among women than men (Table 1).3 A Canadian study reported that 4% of Canadian boys in grade nine and ten used anabolic steroids. Use of ana- bolic steroid in males may be an indicator of body preoccupation. The estimated rate of anorexia nervosa and bulimia nervosa in males is between 5% and 15%.4 Men’s reluctance to be diagnosed with eating disorders or to participate in the study of eating disorders have been a big chal-

lenge; consequently, rate of eating dis- orders in males may be higher than it is reported. According to a 2002 survey, prevalence of eating disorders is 1.5% among Canadian women aged 15–24 years.5 Another Canadian survey in 2002 indicated that 28% of girls in grade nine and 29% of girls in grade ten showed weight loss behaviors.4

Impact of Eating Disorders on the Canadian Economy

Although eating disorders mostly re- ceive community treatment, hospital- ization may be needed for severe cases. In-patient crude hospital separations for any diagnosed eating disorders have in- creased by 4.7% between 1994 and 1999 in Canada (Canadian Institute for Health Information, 1999). Despite decrease in hospitalization duration for eating dis- orders between 1987 and 1999 reported by the Center for Chronic Disease Preven- tion and Control, Public Health Agency for Canada reported increased rates of hospitalization for eating disorders among women in general hospitals. In 2005/2006, hospitalization rate for ado- lescence girl with eating disorders were 2.5 times the rate of young women and 6 times the rate of any other groups (Canadian Institute for Health Informa- tion, 2008). The increase in the rate of hospitalization could be due to either increased cases of inpatient treatment or

table 1: Prevalence rates of eating disorders.

Eating Disorders Women Men

Anorexia nervosa (AN) 0.9% 0.3%

Bulimia nervosa (BN) 1.5% 0.5%

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higher rate of eating disorders, or com- bination of two factors. Further studies are required to clarify exact cause(s) of increased rate of hospitalization for eat- ing disorders in Canada. In 1993 physi- cian billing data, hospitalization data, and self-reported productivity losses were used to estimate mental illness cost to Canadian economy. It was estimated that the cost of mental illnesses was $7.331 billion in 1997.6

Although eating disorders are among the mental illnesses that occasionally require hospitalization since hospitalization rate is increasing, even if costs of outpatient services are not taken into account, eat- ing disorders can have a considerable im- pact on the Canadian economy. The exact estimation of economic burden of mental illness including eating disorders would be a big challenge, because of a lack of accurate data both on cost of services and productivity losses.

Mortality Rate in Eating Disorders

Anorexia nervosa has the highest mortal- ity rate of any other mental illnesses. It is estimated that 10% of people with an- orexia nervosa die within 10 years of the onset of disorder (Sullivan, 2002). One study showed the mean crude mor- tality rate of 5.0% for anorexia nervosa. In the surviving patients, on an average, only 46.9% of patients had full recovery, while 33.5% improved, and 20.8% had a chronic course of disease.7,8 Based on total sample of 196 female with buli- mia nervosa, the mean crude mortality

rate was 2.0% for bulimia nervosa.10 A lower standardized mortality rate (the ratio of the observed number of deaths to the expected number of deaths in a matched population) for anorexia ner- vosa compared to normal populations is reported by some studies. However, a recent Canadian study that assessed 326 patients diagnosed with anorexia ner- vosa for 20 years showed a higher mor- tality rate for anorexia nervosa patients than normal populations in Canada.11,12 The challenges that this study faced over 20 years of follow up are: disconnection of cases with research group because of moving outside the British Columbia province; reassessment of previously di- agnosed cases of eating disorders three times over 20 years based on three differ- ent revisions of DSM-IV that could have led to removal of few cases from study after a long term follow up.

Psychiatric Co-morbidity in Eating Disorders

Various psychiatric co-morbidities such as depression, anxiety disorder, obsessive- compulsive disorder, substance abuse, attention-deficit hyperactivity disorders, and personality disorders are prominent in patients with eating disorders. Suicide and suicide attempts are dangerous co- morbidities in eating disorders. Although primary cause of pre-mature death in eat- ing disorders are medical co-morbidities, a meta-analysis that combined the results of 42 published studies of mortality of eat- ing disorders determined that the second

most common cause of death in eating disorders is suicide.7 About 10% to 20% of patients with anorexia nervosa and 25% to 35% of patients with bulimia nervosa have a history of at least one suicide attempt. Standardized mortality rate for suicide in anorexia nervosa is estimated to be up to 5 or even more.11 According to the statis- tics from public health agency of Canada, suicide is the eleventh cause of death in Canada, and more than 3,500 suicides, at a rate of about 11 per 100,000 are re- corded per year. Eating disorders clearly contribute to suicide rates in Canada. An accurate suicide rate of eating disorders is very difficult because of unreliability of suicide statistics in general, difficulties in uncovering the exact cause of death, and undiagnosed cases of eating disorders who commit suicide.

Medical Co-morbidity in Eating Disorders

Wide range of medical complications such as anemia, endocrine system dysfunction, electrolytes disturbances, and cardiovas- cular diseases accompany eating disor- ders. Severity of medical complications depend on speed of weight loss, severity of underweight, duration of eating disor- ders, age of patients, and the intensity of purging (Table 2).11

Etiology of Eating Disorders

Biological Factors

Genetic effects: A growing body of twin studies confirmed that there is an unde- niable link between genetic factors and eating disorders. One of the twin study,

table 2: Medical alterations in adolescent eating disorders.

AN bN

Physical examination findings Dry skin, lanugo hair formation (only with severe weight loss), acrocyanosis, alopecia, low body tem- perature, dehydration, retardation of growth and pubertal development

Erosion of dental enamel, parotid/salivary gland en- largement, scars on the skin of the back of the hand resulting from inducing the gag reflex, dehydration

Cardiovascular system Bradycardia, ECG abnormalities (mostly prolonged QT-interval), pericardial effusion, edema (before or during refeeding)

ECG-abnormalities (cardiac arrhythmia, prolonged QT- interval)

Gastrointestinal system Impaired gastric emptying, pancreatitis, constipa- tion Leukocytopenia, thrombocytopenia,

Esophagitis, pancreatitis, delayed gastric emptying

Blood thrombocytopenia, anemia

Hypokalemia, hyponatremia, hypomagnesiemia, hy- pocalcemia, hypophosphatemia (during refeeding), low glucose levels,

AST↑, ALT↑ (with severe fasting or beginning of refeeding), cholesterol ↑

Hypokalemia, hyponatremia, hypomagnesiemia (caused by diarrhea), hypocalcemia, metabolic alka- losis (in case of severe purging), metabolic acidosis (in case of severe laxative abuse)

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in which twenty- six twins with anorexia nervosa including 13 twins (7MZ, 6DZ) with threshold and 13 twins (7MZ, 6DZ) with sub-threshold anorexia nervosa were studied,13 neither of DZ twins met the criteria for diagnosis of anorexia nervosa, while 29%–50% of MZ twins were concordant for anorexia nervo- sa. Although some of the twin studies believe that contributions of shared en- vironmental effects (the same family en- vironment in which twins grow up), and non-shared environmental effects (nega- tive life events) are often small but these effects were also included in the reported twin studies.

One of the limitations of twin study could be due to the short follow up period. Some cases that are not concordant may turn to be concordant later, and unaccounted cases can affect heritability estimate for eating disorders. Small sample size is an- other limitation in twin studies that pro- hibits researchers to study wide range of non-shared and shared environmental effects, and probably overestimates rate of heritability. Study of larger sample size that preferentially includes different racial groups would be more useful.

Neurobiology

Serotonin (5-hydroxytryptamin, 5HT) is believed to participate not only in appetite regulation but also in mood regulation. Altered tone or transmission of serotonin mediates anxiety reaction, problem with response inhibition, aggression, suicidal- ity, heightened vigilance, and self-injury.14 Although exact cause of 5-HT dysfunction in eating disorders is unknown, but sev- eral studies presumed that alteration of 5-HT1A and 5-HT2A receptor activities, the 5-HTT (5-HT transporter), and CSF 5-HIAA levels can be involved in patients with eat- ing disorders.15 Several studies confirmed persistence of alterations in serotonin ac- tivity,16,17 and also persistence of anxiety, perfectionism, and obsessive behavior18 after recovery from anorexia nervosa and bulimia nervosa.

Regarding these findings, serotonin may indirectly mediate its effects on develop- ment of eating disorders through some personality traits that are prominent in patients with eating disorders. Study of subtle differences in patterns of function- al alteration of serotonin in subjects with pre-morbid personality traits without eat- ing disorders, and in subjects with eat- ing disorders without these personality traits may be helpful though sample size

would be small in this group. Data col- lection related to pre-morbid personality traits would be highly desirable. Interest- ingly, one experimental study showed alteration of mesolimibic dopamine and serotonin as a result of restricted eating coupled with excessive exercise in activi- ty-based anorexia model.19 Based on this observation, it can be concluded that ab- errant eating behaviors can potentially alter serotonin function and therefore result in persistence of functional altera- tions of serotonin after recovery of eating disorders. Neither of the studies inter- rogated persistence of functional altera- tions of serotonin as a “scar of prolonged aberrant eating behavior”. Although, study of possible functional alterations of serotonin due to aberrant eating behav- iors is costly and invasive, but it would contribute to understanding complex re- lationship between functional alterations of serotonin and eating disorder.

Though one previous study suggested heritability of functional alterations of se- rotonin by showing anomalous peripheral uptake of serotonin in unaffected first-de- gree relatives of bulimia nervosa patients20

but functional alterations of serotonin can be still considered as an outcome of aber- rant eating behavior in patients. Further studies are required to confirm heritability of abnormalities of serotonin functions in eating disorders. To differentiate abnor- malities of serotonin due to heritability from those due to aberrant eating behav- iors, study of serotonin function in sus- pected subjects before the onset of eating disorders may be useful.

Psychology Factors

Body image disturbance

Body cachexia, the degree of body satis- faction and dissatisfaction is believed to be an integral part of self-esteem. Indi- viduals assess their bodies by measuring them against ideal body type of culture. The result of this self-assessment deter- mines body satisfaction or dissatisfac- tion.21 A prospective study on college freshman women showed that figure dis- satisfaction, ineffectiveness and, public self-consciousness were associated with symptoms of eating disorders.22 Since the body dissatisfaction data collection was done after development of eating disor- ders in this study, body dissatisfaction could be a predictor for worsening of eat- ing symptoms rather than a predictor for development of eating disorders. Striegel- moore et al. also showed that severity of

body dissatisfaction are correlated with worsening of disordered eating in sample of first year college women.20 Another Study disproved body image disturbance as a predictive of later eating disorders af- ter 2 years follow up of college students.21 Considering to changes in patterns of thinking due to developmental process, studies that begin to collect data in very early adolescence, and follow up patients into adulthood may be more informative.

Another useful approach is the study of body dissatisfaction in subjects who al- ready recovered from eating disorders (recovered study design). Regardless of the fact that eating disorders are known as psychiatric disturbances with persistent residual symptoms, this type of study could define the role of body dissatisfac- tion either as an etiology or as a clinical feature of eating disorders. Examination of other variables that decrease or increase the risk of eating disorders may overcome lack of unanimous agreement about role of body dissatisfaction in development of eating disorders. Stice et al. opposed the role of body image disturbances in development of eating disorder because they believe that body dissatisfaction is a risk factor for depression.23 Regarding this notion, concurrent depression should be carefully assessed in patients with eating disorders when studying body dissatisfac- tion as a risk factor for eating disorders.

A Canadian survey showed that 34% of adolescent girls and 24% of adolescent boys in Grades 6 to 10 thought that they were too obese. This notion increased among adolescent girls from 25% in grade 6 to 40% in grade 10, while only 15% were actually obese (Public Health Agency of Canada, 2008). Regarding significant num- ber of students with body dissatisfaction, prospective studies are required to find out what percentage of these Canadian ado- lescent girls and boys will develop full pic- ture of eating disorders later. In addition to huge amount of budget required, this study may face another big challenge that is convincing adolescent girls and espe- cially boys to participate in this study. This study helps health care system in Canada to plan prevention, early diagnosis, and treatment of potential future patients with eating disorders in advance.

Personality traits

Role of personality disorders in the de- velopment of eating disorders has been the center of attention for many re- searchers. Several studies have found

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that personality traits such as impul- sivity, novelty seeking, stress reactiv- ity, harm avoidance, perfectionism, and other personality traits are common in patients with eating disorders. Most of these studies assessed personality traits in their subjects during illness. Therefore, their personality traits could be a reflec- tion of adverse effects of starvation.24

A study shows the effect of starvation and recurrent binge and purging on de- velopment of anxiety, social withdrawal, and irritability in previously normal peo- ple only a few weeks after restricted food intake (Keys et al., 1950). Numerous stud- ies used personality inventories such as Eating Disorder Inventory (EDI) to assess specific cognitive and behavioral dimen- sions of eating disorders such as drive for thinness, bulimia, body dissatisfaction ineffectiveness, perfectionism, interper- sonal distrust, interceptive awareness, and maturity fear. Personality inventories are designed for the assessment of adult populations. Consequently use of these inventories for assessment of personal- ity traits in majority of subjects with eat- ing disorders who are typically in early adolescent may not be appropriate.24 One important factor that could have possible effect on the accuracy of results in the study of personality traits in adolescences is the constantly changing patterns of perception about the environment and oneself due to ongoing developmental changes in personality. Medical and non- medical therapy in patients with chronic eating disorders could also affect post- morbid functions and personality traits of these patients. Interestingly some studies show the changes in behavior patterns such as harm avoidance, persistence, self- directedness, and self-transcendence af- ter in-patient Cognitive Behavioral Ther- apy (CBT) for eating disorders.11 Future researches should be aware of the effects of therapy on the result of study of per- sonality traits in eating disorder cases.

Developmental factors

Childhood sexual abuse

Despite the fact that childhood sexual (CSA) abuse as a risk factor for eating

disorders has been a source of debate among clinicians and researchers. While some studies showed strong relationship between CSA and eating disorders, some other studies strongly refuse to accept this relationship. Discrepancy between the results of various studies could be due to the non-uniformity in definition of CSA. Al- though association between different psy- chiatric disorders with severity of trauma due to CSA is not well understood yet, but different severity of CSA ranging from non- touching, single episode to long-term sex- ual abuse combined with physical abuse reported by victims may affect the result of studies. The entry time of sexually abused subjects with eating disorders into the study should also be considered. If the gap between the development of eating disor- ders and occurrence of sexual abuse is very short, subjects may not be recovered from memories of such a horrible experience. Severity of eating disorders might also af- fect their sexual abuse reports. In severe forms of eating disorders, CSA experience may be inaccessible to victims.26 Increase in the rate of CSA reported between 1998 and 2003 in Quebec27 (Table 3) could be a warning sign for increased rate of psychi- atric problems including eating disorder in Canada. A well-designed research project with consideration on the subject’s ethnic origins, age at the time of sexual abuse, socioeconomic class, and family dynamics could contribute to the understanding of possible relationship between CSA eating disorder with CSA. The challenges this re- search may face are accuracy of data, care- ful examination of other variables, lack of victims’ confidence to report the abuse to police or to child protection system, and clear definition of CSA. This study could also suffer from the problem of cost effec- tiveness.

socio-Cultural Factor

Western cultural influence

Exposure to western culture that values slim body for women is presumed to play an important role in the increased eating disorders worldwide. Rate of eating disor- ders in countries such as Japan, Iran, and

Singapore continues to increase among women who have been exposed to west- ern culture through temporary living in western countries for education, or even short-time vacation, or through mass me- dia.28,29 Increase in the rate of eating dis- orders in populations exposed to western culture in those countries could strongly support the role of western culture in the development of eating disorders. Study of effects of western culture in relation to incidence of eating disorders in non- western immigrant women and girls has been recently given special attention. Swanson et al. studied binge eating (BED) disorder in Mexican immigrants to U.S.30 Although anxiety and depression may not be etiology of BED, they adjusted prior anxiety and depression that could act as non-specific markers of high risk for psychopathology. This study showed significantly increased rate of BED in U.S born Mexican with two U.S born parents. This study also concluded that cultural in- fluence underlying in the increased rate of BED occurs slowly. Most of the stud- ies failed to control at least one variable such as socioeconomic status especially family income, which may have a posi- tive correlation with body dissatisfaction, age differences, despite strong link be- tween age and eating disorders.31 Usage of English language at home and religion could also be a potential cause of higher tendency for thinking about dieting and body shape, and as an indicator of accul- turation.32,33

Another study demonstrated that as gen- erations further removed from immigra- tion experiences, influence of western culture on body ideals and standards be- comes prominent. In this study native Canadian born woman with one or no immigrant parent already completed ac- culturation had higher tendency to think about dieting than immigrant women or native-born women with two immigrant parents. Acculturation in this paper was de- fined as the adoption of Canadian values, lifestyle habits, particularly, eating habits, and dietary preferences. As far as develop- ment of eating disorders is concerned, the

table 3: Changes in incidence rates of substantiated child sexual abuse, physical abuse, and neglect cases between 1998 and 2003 in the child protection services of the United states, Canada, and two Canadian provinces.27

United states Canada Ontario Quebec

Sexual abuse  20%  30%  18%  24%

Physical abuse  22%  107%  84%  70%

Neglect  17%  78%  103%  38%

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term “acculturation” is referred to adop- tion of negative aspects of Canadian eat- ing and lifestyle habits similar to the symp- toms of eating disorders, especially BED.32 Although this research group carefully considered effects of family income, age differences, and English-speaking at home, but neither of the subjects in this study ful- filled diagnostic criteria for eating disorders based on DSM-IV criteria. This study also failed to control psychobiological factors that might possibly make the subjects vul- nerable to sociocultural pressures.

A large population of immigrants in Canada coming from non-western coun- tries provides an excellent opportunity to study influences of western culture on different ethnic origins with different re- ligious affiliations, socioeconomic status, and eating habits.

This study could contribute to better un- derstanding of connection between west- ern culture and eating disorders. Careful examination of a broad range of non- specific factors that result in psychiatric disorders associated with immigration in immigrant patients with eating disor- der and their family may be a challenge for this study. Study of gene influence, particularly, in generations of families of mixed heritage with eating disorders is highly recommended.

Conclusion

It has been hypothesized that eating dis- orders have multiple and often shared eti- ologies including biological, psychological, developmental, and sociocultural. A tightly woven network of causes, symptoms, and outcomes of eating disorders makes the study of etiology of these disorders very challenging. Some suggested risk factors for eating disorders require to be defined as either integral parts of eating disorders syndrome such as body dissatisfaction, and perfectionism or outcome of pro- longed disordered eating such as function- al alterations in serotonin, and some mood disturbances. Researchers should structure their thought processes around this con- cept that some of currently well-known risk factors for eating disorders are concur- rent symptoms of eating disorders. Hence paying special attention to the new and evolved concepts is highly recommended while studying the etiology of eating dis- orders.

The article complies with International Committee of Medical Journal editor’s uniform requirements for manuscript.

Conflict of Interests: None; Source of funding: None.

Received Date: 12 September 2013; Revised Date: 11 November 2013; Accepted Date: 20 December 2013

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