Executive functioning in anorexia nervosa patients and their unaffected relatives
Introduction
Anorexia nervosa (AN) is characterized by disordered eating behaviors where the patient's attitudes toward weight and shape, as well as their perception of body shape, are disturbed (American Psychiatric Association, 2000). It has been suggested that the clinical phenomena seen in AN reflect executive functioning impairments (Frampton and Hutchinson, 2007). For example, AN patients persist in restrictive behaviors despite serious risks to their health (Fairburn et al., 1999) and despite psychosocial consequences. These pathological eating behaviors reflect their preference to opt for choices that yield high immediate gains in spite of higher future losses, and they can be conceptualized in term of impairments in planning real-life strategies and decision-making abilities (Cavedini et al., 2004). Furthermore, AN patients are characterized by rigidity, perfectionism, compulsive traits, and need for control. These characteristics could be the results of set-shifting impairments (Tchanturia et al., 2012). An increasing number of neuropsychological studies have investigated the relationship between executive functions and disordered eating behaviors (Braun and Chouinard, 1992, Lauer, 2002, Duchesne et al., 2004, Southgate et al., 2005, Tchanturia et al., 2005). Consistent findings have emerged for set-shifting (Tchanturia et al., 2002, Tchanturia et al., 2004, Tchanturia et al., 2012) (for review see Roberts, et al., 2007) and central coherence (Lopez et al., 2008). Poor set-shifting has also been found in unaffected sisters of women with AN, providing some evidence for this cognitive feature as a candidate endophenotype (Holliday and Tchanturia, 2005, Roberts et al., 2010, Tenconi et al., 2010). Deficient decision-making has been reported in AN patients (Cavedini et al., 2004, Cavedini et al., 2006, Tchanturia et al., 2007), but recently Guillaume et al. (2010) found normal decision making in these patients, so this neuropsychological domain needs further elaboration. Unfortunately, even if AN pathological eating behaviors strongly suggest an impairment in planning strategies, only one study has investigated this function (Fowler et al., 2006) and no study has been conducted on their unaffected relatives.
At present, findings regarding executive dysfunctions in AN patients remain unclear and many question that remains to be resolved. Particularly, there is uncertainty regarding the reversibility of some neurocognitive impairments after re-feeding. Thus, whether executive deficits are state or trait related is a question still unresolved (Lindner et al., 2012, Cavedini et al., 2006).
The use of endophenotype approach may facilitate our understanding of AN executive functioning and pathophysiology. In the last few years, neurocognitive dysfunctions have been considered among the most promising endophenotype candidates in many psychiatric disorders (Leboyer, 2003, Flint and Munafo, 2007, Bulik et al., 2007). This approach is an attractive strategy for the exploration of genetic predisposition because endophenotypes represent a means of dissecting the clinical phenotype into biological variables that are hypothetically more proximal to genetic effect (Leboyer, 2003, Flint and Munafo, 2007). This aspect is even more important if one takes into account that several decades of trying to discover causative genes in AN have, as yet, yielded disappointing results (Slof-Op't Landt et al., 2005, Scherag et al., 2010, Clarke et al., 2012).
Endophenotypes have to be heritable, co-segregating with a psychiatric clinical phenotype in the general population, state independent, and present in unaffected family members at a higher rate than in the general population (Flint and Munafo, 2007). Specific susceptibility gene variants may underlie endophenotypes, which in turn may predispose individuals to develop AN and related conditions. If a characteristic fulfils these criteria but is not proven to be heritable, it is termed a “biological marker” (Holliday and Tchanturia, 2005).
This study was designed to explore simultaneously planning, set-shifting and decision-making in AN patients and their unaffected first degree relatives. We used a test battery composed by the Tower of Hanoi (ToH), the Wisconsin Sorting Card Test (WCST) and the Iowa Gambling Task (IGT). We analyzed the proband/relative concordance rates for the cognitive performances. This is a relatively novel approach and could be useful to better understand the familiality of the neurocognitive traits, but it should not be considered as a measure of heritability since all family members live/lived in the same household and share genes as well as environments. To better understand if these executive functions could be considered a candidate endophenotype for AN, we calculated heritability indices (h2) using a parent–offspring regression model.
Finally, instead of looking at each neurocognitive performance separately, we analyzed the combination of performances together in order to define complex neurocognitive profiles. Results from this study might provide further supporting evidence for the possible qualification of planning, decision-making and set-shifting performance as a candidate endophenotype for AN.
Section snippets
Subjects
The study sample consisted of 116 subjects: 29 pairs of AN probands and their unaffected first-degree relatives and 29 pairs of healthy comparison probands and their unaffected first-degree relatives. All participants were female. The AN relatives group consisted of 18 mothers and 11 sisters. In the HC relatives group, there were 15 mothers and 14 sisters.
AN probands were recruited consecutively from a clinical population referred to the Department of Neuropsychiatric Sciences, San Raffaele
Demographic and clinical characteristics
Means±Standard Deviation for demographic and clinical characteristics are shown in Table 1. AN and HC probands were equivalent in age (F(1,56)=3.09; P=0.08) and educational level (F(1,56)=1.31; P=0.25). The same results were obtained comparing AN and HC relatives [Age: F(1,56)=0.01, P=0.89); Educational level: (F(1,55)=0.59, P=0.44)]. We found differences for age but not for education comparing AN and HC probands to their respective relatives [AN: Age (F(1,56)=50.06; P=0.0000); Education: (F
Discussion
The aim of this study was to examine decision-making, planning and set-shifting in AN patients and their unaffected first-degree relatives. The Iowa Gambling Task (IGT), the Tower of Hanoi (ToH) and the Wisconsin Card Sorting Test (WCST) were administered to all participants.
Results showed that both AN patients and their unaffected relatives performed significantly worse than the HC and their relatives on the IGT and rhe WCST, suggesting that deficient decision-making and set-shifting
Acknowledgments
All of the authors would like to thank Dr. Valentina Scavelli, Dr. Valentina Sani, Dr. Silvia Fronza and Dr. Alessandra Bosaia working at the Center for Obsessive-Compulsive Spectrum Disorders, Department of Clinical Neurosciences, San Raffaele Scientific Institute, for their help in collecting the data.
Elisa Galimberti conducted this study as partial fulfillment of her PhD in Molecular Medicine, Program in Experimental Neurology, San Raffaele University, Milan, Italy
References (51)
- et al.
Developmental and genetic influences on prefrontal function in adolescents: a longitudinal twin study of WCST performance
Neuroscience Letters
(2010) - et al.
Insensitivity to future consequences following damage to human prefrontal cortex
Cognition
(1994) - et al.
Neuropsychological investigation of decision-making in anorexia nervosa
Psychiatry Research
(2004) - et al.
Decision-making functioning as a predictor of treatment outcome in anorexia nervosa
Psychiatry Research
(2006) - et al.
Executive dysfunctions in obsessive-compulsive patients and unaffected relatives: searching for a new intermediate phenotype
Biological Psychiatry
(2010) - et al.
A cognitive behavioural theory of anorexia nervosa
Behaviour Research and Therapy
(1999) - et al.
Psychiatric diagnoses and personality traits associated with disadvantageous decision-making
European Psychiatry
(2007) - et al.
The Yale–Brown-Cornell Eating Disorder Scale: development, use, reliability and validity
Journal of Psychiatric Research
(1994) - et al.
Exploring the neurocognitive signature of poor set-shifting in anorexia and bulimia nervosa
Journal of Psychiatric Research
(2010) - et al.
Cognitive flexibility in verbal and nonverbal domains and decision making in anorexia nervosa patients: a pilot study
BMC Psychiatry
(2011)
Diagnostic and Statistical Manual of Mental Disorders. Text Revision
A simple objective technique for measuring flexibility in thinking
Journal of General Psychology
Neuropsychological study of underweight and “weight-recovered” anorexia nervosa compared with bulimia nervosa and normal controls
International Journal of Eating Disorder
Is anorexia nervosa a neuropsychological disease?
Neuropsychology Review
Anorexia, bulimia, and obesity: shared decision making defi cits on the Iowa Gambling Task (IGT)
Journal of the International Neuropsychological Society
Genetic epidemiology, endophenotypes, and eating disorder classification
International Journal of Eating Disorders
The genetics of anorexia nervosa
Clinical Pharmacology and Therapeutics
Neuropsychology of eating disorders: a systematic review of the literature
Revista Brasileira de Psiquiatria
Introduction to Quantitative Genetics
The endophenotype concept in psychiatric genetics
Psychological Medicine
Profile of neurocognitive impairments associated with female in-patients with anorexia nervosa
Psychological Medicine
Eating disorders and the brain
Is decision making really impaired in eating disorders?
Neuropsychology
Is impaired set-shifting an endophenotype of anorexia nervosa?
American Journal of Psychiatry
The influence of four serotonin-related genes on decision-making in suicide attempters
American Journal of Medical Genetics Part B
Cited by (85)
Cognitive flexibility and the risk of anorexia nervosa: An investigation using self-report and neurocognitive assessments
2022, Journal of Psychiatric ResearchExecutive function in obesity and anorexia nervosa: Opposite ends of a spectrum of disordered feeding behaviour?
2021, Progress in Neuro-Psychopharmacology and Biological PsychiatryA review of effort-based decision-making in eating and weight disorders
2021, Progress in Neuro-Psychopharmacology and Biological PsychiatryCurrent directions in biomarkers and endophenotypes for anorexia nervosa: A scoping review
2021, Journal of Psychiatric Research