Although the origin, treatment, course, and outlook of anorexia nervosa (AN) have remained a puzzle, advances in at least 11 areas have helped us better understand this disease.

Genetic Links
Important multicenter studies on the genetics of anorexia nervosa are underway to compare vulnerable patients with their siblings and parents, and to sort out clusters of genes that increase vulnerability to anorexia nervosa. Unlike Huntington’s disease, for example, the genetics of AN do not determine whether one gets the disease. However, genetics probably do provide a crucial predisposition to AN through abnormalities of serotonin and metabolism and their effects on personality, reactivity, perseverance, and perhaps weight control, hunger, and satiety.

The Brain as a Mirror
The brain is clearly affected structurally and functionally as a consequence of AN. Several studies have confirmed the significant effects of self-starvation on the brain. With starvation, the ventricles of the brain increase in size and the cortical mass decreases. One matter of concern is the fact that there is improvement, but not complete normalization, of gray and white matter as long as 6 to 12 months after weight restoration. The very powerful imaging tools of functional MRI and PET scans are demonstrating a change in the interaction between the prefrontal cortex and components of the limbic system in regard to the sensing and perpetuation of emotional distress in active AN. These tools will not only demonstrate the effects of eating disorders but will also document the relative benefits of a variety of treatments.

Critical Diagnostic Criteria
In another development, diagnostic criteria for anorexia are being reviewed with a goal of sorting out the critical features and introducing more flexibility for traditional but perhaps out-of-date criteria. Including amenorrhea as a criterion for AN is less useful than noting abnormalities of reproductive hormone function in general. Broader recognition of medical consequences of starvation not limited to levels of reproductive hormones is even more useful. The key concept here is that AN involves self-starvation to a substantial degree below the individual’s usual or healthy weight. Some people may be semi-starved even if their hormone levels are normal and they are at their normal weight. This means that amenorrhea is not as important as are general measures of self-starvation, and that a final lowest weight of 85% of normal healthy weight is not as crucial as is a significant decline in weight from an initial healthy weight.

Men Develop EDs, Too
A recent large epidemiologic study has substantiated that males are probably underrepresented in both epidemiologic and clinical studies. While earlier studies reported ratios of as many as 10 females to 1 male, a ratio of one male to three or four females may be more accurate. This raises concerns that males are underrepresented in clinical programs, and calls for better understanding of the factors that may be keeping them from seeking treatment.

Axis I Comorbidities
The recognition that AN usually has associated comorbidities on Axis I or II has been confirmed with awareness that AN seldom presents by itself but there is a high probability of Axis I diagnoses, including comorbid depression, anxiety, and substance use disorders. On Axis II, there is an overrepresentation of cluster C for restricting AN and a mixture of clusters B and C for AN binge-purge subtype. Recent studies from Denmark have highlighted the especially deadly combination of AN with insulin-dependent diabetes mellitus in young individuals. These studies spell out an approximately tenfold increase in mortality with this combination, compared to having either of these disorders alone.

The Rise of Neuroleptics
A number of trials are underway using atypical neuroleptics such as risperidone and olanzapine. The hope is that they will have an effect on the core psychopathology of AN rather than merely stimulating weight gain, as was the case with chlorpromazine in the 1960s.

An Excellent Outcome May Be Possible for Many
Although AN is often considered a chronic disorder with a poor prognosis, in fact the duration of AN is quite variable, and more than 75% of patients will have an excellent outcome. This is especially true for adolescent anorexics who are treated comprehensively to full weight restoration with associated cognitive behavioral psychotherapy, and then followed up carefully. A 10-year follow-up study at UCLA documented complete improvement with absence of any diagnostic features for any eating disorder in 76% of patients.

Insurance Limitations
Despite improvements in outcome with modern treatment modalities, many patients cannot get access to treatment because of irrational insurance limitations. Decreasing length of hospital stays, an increasingly common occurrence with restrictive and irrational insurance limitations, is leading to more frequent relapse and less sustained improvement. Groups such as the Eating Disorders Coalition have been working to change this.

Arguments Over Effectiveness of Prevention Efforts
Controversy exists between clinicians, between treatment centers, and between countries on the possible effectiveness of preventive efforts in AN. Several studies are now suggesting there is a decrease in the prevalence or severity of AN in vulnerable individuals when pressure to lose and maintain an abnormal body weight is removed. For example, there is evidence that the number of cases of eating disorders declines when a strict ballet school refuses to let a dancer participate below a certain weight or when a collegiate wrestler is barred from participating below a certain percent body fat or absolute weight. The more adventurous approach toward empowering young people with media skepticism, with assertiveness, and with improved body image has not yet been tried on a broad-enough population to comment on its effectiveness. But the approach to “inoculating” the vulnerable subgroup of young people with techniques to make their way through a society obsessed with thinness merits continued work.

A Disease That Stands on its Own
There has been some attempt to subsume AN into other diagnostic categories, such as obsessive-compulsive disorder (OCD), major depression, or psychosis. In fact, AN “breeds true,” with evidence that the core syndrome has not changed in hundreds of years. There is ongoing discussion about the presentation in different cultures in regard to the content of the core psychopathology. There is support for the concept that overvalued beliefs are part of the core psychopathology of AN, and that the overvalued beliefs vary from culture to culture. For example, in the West, we overvalue thinness. To further clarify this, overvalued beliefs are defined as culturally normative beliefs that have been assigned disproproportionate values in a particular individual and that demonstrate that individual’s thinking, emotional life, and behavior. Nor are they the type of ego dystonic thoughts or behaviors required for obsessive-compulsive disorders. Although overvalued beliefs are not abnormal themselves, what is abnormal is the excessive value assigned to them. This diagnostic criterion is less frequently used than it should be and helps to differentiate the AN psychopathology from OCD or psychosis and also explains some of the chronicity of the disease. It also offers hope for change through stopping the abnormal behavior and challenging the core overvalued belief with cognitive behavioral techniques.

Family Therapy
There’s exciting evidence that the families of young anorexics may be able to be empowered through teaching techniques to keep the patient from ever being hospitalized, even when very starved, when parents practice a stepwise approach toward changing the self-starvation with caring but firm techniques.