Is Impaired Set-Shifting an Endophenotype of Anorexia Nervosa?

Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK.
American Journal of Psychiatry (Impact Factor: 12.3). 01/2006; 162(12):2269-75. DOI: 10.1176/appi.ajp.162.12.2269
Source: PubMed

ABSTRACT Set-shifting difficulties have been reported in subjects with anorexia nervosa and appear to persist after recovery; therefore, they may be endophenotypic traits. The goals of this study were to investigate whether set-shifting difficulties are familial by examining discordant sister-pairs in comparison with healthy unrelated women and to replicate, with a broader battery, the lack of influence of an acute illness state on neuropsychological performance.
Forty-seven pairs of sisters discordant for anorexia nervosa and 47 healthy unrelated women who were comparable in age and IQ completed neuropsychological 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, anxiety, and depression symptoms. Subjects with acute (N=24) and fully remitted (N=23) anorexia nervosa were compared to assess state versus trait effects.
Sisters with and without anorexia nervosa took significantly longer than unrelated healthy women to shift their cognitive 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 recovered from anorexia nervosa made significantly fewer errors than those with acute anorexia nervosa on the Trail Making alphabet task, but these subgroups did not differ on other measures.
Both affected and unaffected sisters had more set-shifting difficulties 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 endophenotype in anorexia nervosa.

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Available from: Kate Tchanturia, Sep 26, 2015
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    • "Some set-shifting impairments have also been reported in first degree relatives of those with AN. Thus, set-shifting difficulties have been proposed as a possible endophenotype for AN (Holliday et al., 2005). "
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    ABSTRACT: Objectives Recent research suggests certain neuropsychological deficits occur in anorexia nervosa (AN). The role of starvation in these deficits remains unclear. Studies of individuals without AN can elucidate our understanding of the effect of short-term starvation on neuropsychological performance. Methods Using a within-subjects repeated measures design, 60 healthy female participants were tested once after fasting for 18 hours, and once when satiated. Measures included two tasks to measure central coherence and a set-shifting task. Results Fasting exacerbated set-shifting difficulties on a rule-change task. Fasting was associated with stronger local and impaired global processing, indicating weaker central coherence. Conclusions Models of AN that propose a central role for set-shifting difficulties or weak central coherence should also consider the impact of short-term fasting on these processes.
    PLoS ONE 10/2014; 9(10). DOI:10.1371/journal.pone.0110743 · 3.23 Impact Factor
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    • "Abnormalities in the “compulsive” circuit are implied by deficits in neuropsychological tasks thought to tap this construct (see Table 1). Individuals with AN are often described as having low cognitive flexibility (Tchanturia et al., 2004), and consistently show poor set-shifting abilities (Holliday et al., 2005; Steinglass et al., 2006; Bühren et al., 2012). Poor set-shifting has been suggested as an endophenotype of both AN and BN, and is associated with both longer illness duration and increased disorder-related rituals (Roberts et al., 2010). "
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    ABSTRACT: The compulsive nature of weight loss behaviors central to anorexia nervosa (AN), such as relentless self-starvation and over-exercise, has led to the suggestion of parallels between AN and other compulsive disorders such as obsessive-compulsive disorder (OCD) and addictions. There is a huge unmet need for effective treatments in AN, which has high rates of morbidity and the highest mortality rate of any psychiatric disorder, yet a grave paucity of effective treatments. Viewing compulsivity as a transdiagnostic concept, seen in various manifestations across disorders, may help delineate the mechanisms responsible for the persistence of AN, and aid treatment development. We explore models of compulsivity that suggest dysfunction in cortico-striatal circuitry underpins compulsive behavior, and consider evidence of aberrancies in this circuitry across disorders. Excessive habit formation is considered as a mechanism by which initially rewarding weight loss behavior in AN may become compulsive over time, and the complex balance between positive and negative reinforcement in this process is considered. The physiological effects of starvation in promoting compulsivity, positive reinforcement, and habit formation are also discussed. Further research in AN may benefit from a focus on processes potentially underlying the development of compulsivity, such as aberrant reward processing and habit formation. We discuss the implications of a transdiagnostic perspective on compulsivity, and how it may contribute to the development of novel treatments for AN.
    Frontiers in Psychology 07/2014; 5:778. DOI:10.3389/fpsyg.2014.00778 · 2.80 Impact Factor
    • "However, both differences were not statistically significant (Friederich et al., 2012; Nakazato et al., 2009; Roberts et al., 2010; Tchanturia et al., 2004; Tchanturia et al., 2011). In most of these studies, the sample size was rather small (13-30 recAN participants; Danner et al., 2012; Friederich et al., 2012; Holliday et al., 2005; Nakazato et al., 2009; Roberts et al., 2010; Tchanturia et al., 2004; Tchanturia et al., 2002). Tenconi et al. (2010) studied 63 weight recovered and 29 fully recovered AN patients and found no difference from the acutely ill AN patients, that is, the recAN patients showed inefficiencies in set-shifting compared with the healthy control group. "
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    ABSTRACT: Objective First, this study aimed to explore whether set-shifting is inefficient after full recovery of anorexia nervosa (recAN). Second, this study wanted to explore the relation of set-shifting to clinical and personality variables.MethodA total of 100 recAN women were compared with 100 healthy women. Set-shifting was assessed with Berg's Card Sorting Test. Expert interviews yielded assessments for the inclusion/exclusion criteria, self-ratings for clinical and personality variables.ResultsCompared with the healthy control group, the recAN participants achieved fewer categories, showed more perseverations and spent less time for shifting set. Perfectionism is correlated with set-shifting but in converse directions in the two groups.DiscussionOur study supports the findings of inefficiencies in set-shifting after full recovery from AN. Higher perfectionism in the recAN group is associated with better set-shifting ability, whereas higher perfectionism in the healthy control group is related to worse set-shifting ability. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
    European Eating Disorders Review 07/2014; 22(4). DOI:10.1002/erv.2293 · 2.46 Impact Factor
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