Pathogenesis of anorexia nervosa. (2001)

Abstract This paper provides a recent review of studies investigating the eating disorder anorexia nervosa, with a view to summarising current knowledge on the pathogenesis of this condition. Genetic factors, the role of dieting, family functioning, and societal influences are each discussed in turn, and the application of current data to the treatment setting is also outlined. Key words: Anorexia nervosa, Eating disorders Introduction Anorexia nervosa (AN) is an intriguing disorder. Its incidence is increasing in the West, and it is among the most lethal of all psychiatric disorders. (1-4) It seems to selectively affect young, intelligent, attractive women of higher social standing. (5) Within a given society, its prevalence varies among different ethnic groups and increases as a society becomes more westernised. (5) It is a familial disorder. (6) A comprehensive theory of pathogenesis would need to encompass biological, developmental, psychodynamic, familial, and cultural perspectives. The search for such a theory is a daunting task. This article summarises current knowledge concerning the pathogenesis of AN. Bulimia nervosa (BN), a seemingly related condition sharing many of the clinical features of AN, will be mentioned only with regard to findings of relevance to AN. Genetics and Biology There is strong evidence supporting a genetic basis to AN. Three studies have specifically addressed this aspect by studying twin pairs in a clinical setting. (7-9) Holland et al published data on 2 different sets of twins. (7,8) In the first study of 34 twin pairs and 1 set of triplets, pairwise concordance rates of AN were much higher among monozgyotic (MZ) than dizygotic (DZ) twins (55% vs 7%). (7) In the second study of a further 15 female twin pairs, a significant difference between MZ and DZ twins was again found (71% vs 10%). (8) A later German study of 25 twin pairs also reported a similar difference in concordance rates between MZ and DZ twins (57% vs 9%) with respect to AN. (9) Data from 2 of 3 large scale population-based twin studies also support a genetic basis for AN. In the first study, Walters and Kendler administered adapted sections of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-R (SCID-III-R) to 2163 Caucasian female twins on the Virginia twin register. (10) They found that the co-twins of twins with AN were more likely to have a current low body mass index, and also had a significantly higher lifetime risk for AN, BN, and major depression. Wade et al, in an Australian twin register study of 3869 female twins, found that environ-mental rather than genetic influences best explained the weight, shape, and eating concerns seen among twins with BN. (11,12) However, major methodological limitations, including poor case ascertainment undermine the validity of these findings. Data on AN was not reported. In a Danish study, Kortegaard et al sent a questionnaire to 34,142 twins on the Danish twin register. (13) They found a higher pairwise concordance rate for broadly defined AN among MZ twins (15%) than among DZ twins (7%). Again, the method of case ascertainment--case status was determined by 2 questions in a 59-item questionnaire--and the relatively low response rate (82%) overall, weakened the findings. Although these population twin studies have major methodological flaws, the findings do lend support for the role of genetic factors in the pathogenesis of AN. (14) What could be genetically transmitted to make an individual vulnerable to the development of AN? There are a range of possibilities to consider in this regard. The disorder itself could be transmitted similar to other conditions such as neurofibromatosis. However, it is unlikely that AN is the result of a single, dominant gene inheritance pattern, and such direct inheritance would still leave unexplained the biological mechanisms producing extreme dieting behaviour, and the characteristic mental attitude of weight phobia. …