عملکرد اجرایی در بیماران بی اشتهایی عصبی و عدم تاثیر پذیری بستگان آنها
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|33792||2013||7 صفحه PDF||سفارش دهید||6639 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Psychiatry Research, Volume 208, Issue 3, 15 August 2013, Pages 238–244
Formal genetic studies suggested a substantial genetic influence for anorexia nervosa (AN), but currently results are inconsistent. The use of the neurocognitive endophenotype approach may facilitate our understanding of the AN pathophysiology. We investigated decision-making, set-shifting and planning in AN patients (n=29) and their unaffected relatives (n=29) compared to healthy probands (n=29) and their relatives (n=29). The Iowa Gambling Task (IGT), the Tower of Hanoi (ToH) and the Wisconsin Card Sorting Test (WCST) were administered. Concordance rates and heritability indices were also calculated in probands/relatives. Impaired performance on the IGT and the WCST were found in both AN probands and their relatives, although planning appeared to be preserved. The IGT heritability index suggested the presence of genetic effects that influence this measure. No evidence for genetic effects was found for the WCST. The results suggest the presence of a shared dysfunctional executive profile in women with AN and their unaffected relatives, characterized by deficient decision-making and set-shifting. Concordance analysis strongly suggests that these impairments aggregate in AN families, supporting the hypothesis that they may constitute biological markers for AN. Decision-making impairment presents a moderate heritability, suggesting that decision-making may be a candidate endophenotype for AN.
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 and Tchanturia et al., 2005). Consistent findings have emerged for set-shifting (Tchanturia et al., 2002, Tchanturia et al., 2004 and 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 and Tenconi et al., 2010). Deficient decision-making has been reported in AN patients (Cavedini et al., 2004, Cavedini et al., 2006 and 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 and 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 and 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 and 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 and 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.