Is Impaired Set-Shifting an Endophenotype of Anorexia Nervosa?

Joanna Holliday, Ph.D.Kate Tchanturia, Ph.D.Sabine Landau, Ph.D.David Collier, Ph.D.Janet Treasure, M.D., Ph.D., F.R.C.P., F.R.C.Psych.

Objective: Set-shifting difficulties have been reported in subjects with anorexia nervosa and appear to persist after recov- ery; therefore, they may be endopheno- typic traits. The goals of this study were to investigate whether set-shifting difficul- ties are familial by examining discordant sister-pairs in comparison with healthy un- related women and to replicate, with a broader battery, the lack of influence of an acute illness state on neuropsychologi- cal performance.

Method: Forty-seven pairs of sisters dis- cordant for anorexia nervosa and 47 healthy unrelated women who were com- parable in age and IQ completed neuro- psychological tasks selected to assess set- shifting ability. Analyses of variance with standard errors that are robust against correlations within family clusters were used to compare the groups. Results were adjusted for obsessive-compulsive, anxi- ety, and depression symptoms. Subjects with acute (N=24) and fully remitted (N=23) anorexia nervosa were compared to assess state versus trait effects.

Results: Sisters with and without anorexia nervosa took significantly longer than un- related healthy women to shift their cogni- tive set (CatBat task) and demonstrated greater perceptual rigidity (Haptic Illusion task) but did not differ significantly from each other. Women with anorexia nervosa were slower than other groups on Trail Making tasks. Women who had fully recov- ered from anorexia nervosa made signifi- cantly fewer errors than those with acute anorexia nervosa on the Trail Making al- phabet task, but these subgroups did not differ on other measures.

Conclusions: Both affected and unaf- fected sisters had more set-shifting dif- ficulties than unrelated healthy women. This finding, together with the replicated finding that set-shifting difficulties persist after recovery, suggests that set-shifting difficulties are trait characteristics and may inform the search for the endophe- notype in anorexia nervosa.