Cognitive set-shifting in anorexia nervosa.

Research in anorexia nervosa (AN) has indicated that treating youth with the disorder is more successful than treating older individuals with AN (Fisher, 2003), but the reasons for this phenomenon are unknown. The generally young age of onset of AN suggests potential developmental aspects of this disorder (i.e. specific vulnerabilities) relating to the developing brain and body. However, such factors that distinguish younger from older individuals with AN have not been well studied. Recently, the concept of endophenotypes has been developed, which aims to move from the overt behavioural symptoms of an illness to more stable and genetically determined phenotypes (Gottesman & Gould, 2003). By definition, endophenotypes must be associated with the illness, heritable, primarily state independent and familial. The identification of such endophenotypes in AN can potentially guide the development of more specific and effective treatments. For AN, inefficient cognitive set-shifting is a potential endophenotype (Tenconi et al., 2010) Set-shifting is a neurocognitive concept that refers to the ability to switch tasks flexibly or the mental ability to change behaviour in relation to changing rules. Several studies found that women ill with AN have set-shifting inefficiencies (Tchanturia et al., 2011) in that they tend to perseverate on previously applicable rules (Roberts, Tchanturia, Stahl, Southgate, & Treasure, 2007). Such findings are consistent with the clinical observation that these patients tend to be cognitively rigid and persistent (Brewerton, Hand, & Bishop, 1993). Recent evidence suggests that set-shifting inefficiencies not only occur across adults with AN but also other subtypes of eating disorders, such as bulimia nervosa (Roberts, Tchanturia, & Treasure, 2010). Reduced set-shifting has also been found in unaffected relatives of AN patients (Roberts, Tchanturia, & Treasure, 2012) and seems to persist after individuals with AN have restored weight (Tchanturia et al., 2004). Individuals who have maintained long-term recovery from AN (i.e. maintained a stable weight and resumed menses for 1 year; Hambrook et al., 2010; Roberts, Tchanturia, & Treasure, 2010) have also shown set-shifting impairments compared with age-matched healthy controls. These findings further suggest that set-shifting inefficiencies may be an endophenotype of this disease. Given that set-shifting has been associated with brain dopamine (DA) function (Floresco, Magyar, Ghods-Sharifi, Vexelman, & Tse, 2006) and that the pathophysiology of AN may involve DA alterations (Frank et al., 2005; Kaye, Frank, & McConaha, 1999), it is possible that alterations in set-shifting in AN represent changes to the DA system. An important question that arises is whether such inefficiencies are present at all points of the disease. One approach is to examine whether set-shifting inefficiencies are present in young individuals who later develop AN. Such a study would require an epidemiological approach with random sampling of a large set of non-AN individuals and then following them to the development of the disease. Another more feasible approach is to study in a cross sectional design set-shifting in young individuals who have already developed AN and compare them with an adult sample. The literature on cognitive function in youth with AN is not consistent with adult research results. For instance, one study found reduced performance on a sensori-motor task during the underweight state but improved performance with weight restoration. In that same study, adolescents with AN performed superior to healthy controls on working-memory and executive function tasks (Hatch et al., 2010). In contrast to the well-established set-shifting inefficiencies in adults with AN, few studies have examined set-shifting in younger patients with AN. The studies used different designs with inconsistent results, including worse or normal set-shifting performance compared with controls (Dmitrzak-Weglarz et al., 2011; McAnarney et al., 2011; Sarrar et al., 2011). We used a novel, but simple, category learning task that required learning of changing rules, which requires set-shifting ability. The task had a set number of trials both prior to and following the rule change (set-shift), thereby allowing to examine the speed of acquisition of the new rule. This is in contrast to other clinical measures that have been used in the past to examine set-shifting in AN, such as the Wisconsin Card Sorting Test (WCST), where the number of trials prior to a shift requirement is not pre-determined, thereby allowing participants to have a different level of exposure to the initial rule. Versions of this task have been used previously to examine category learning inefficiencies in other patient populations (Filoteo, Maddox, Ing, & Song, 2007). A group of adolescent patients with AN was contrasted with a group of age-matched and gender-matched controls. A group of adult patients with AN was also contrasted with a group of age-matched and gender-matched controls to validate previous results in adult AN. We hypothesized that adolescent AN would display set-shifting inefficiencies similar to adults, with the notion that this cognitive alteration would be an endophenotype independent from age. If adolescent AN patients display similar set-shifting inefficiencies as adult AN patients, it would suggest that this cognitive impairment is observed very early in the course of the disease and may contribute to the development of the disease regardless of age. In contrast, if adolescent AN patients are not impaired, it would suggest that cognitive set-shifting does not contribute to disorder development in the young, whereas still being an important factor for AN in the older age group.