Is Set-shifting And Central Coherence In Anorexia Nervosa .
Fuglset BMC Psychiatry(2021) SEARCH ARTICLEOpen AccessIs set-shifting and central coherence inanorexia nervosa influenced by body massindex, anxiety or depression? A systematicreviewTone Seim FuglsetAbstractBackground: Anorexia nervosa (AN) is a severe eating disorder, recognized by a relentless pursuit for thinness andextreme low body weight. The disorder is often accompanied by comorbid disorders such as anxiety anddepression, and altered neuropsychological function in terms of poor set-shifting and reduced central coherence.The aim of this review was to evaluate whether neuropsychological impairments in AN are influenced by bodymass index, anxiety or depression.Method: A systematic review approach was used, following the PRISMA guidelines for systematic reviews.Literature was identified via searches in PubMed, PsychInfo and Embase database, by using the search words[anorexia nervosa] AND [central coherence], and [anorexia nervosa] AND [set-shifting]. Studies were included ifthey were written in English, peer-reviewed, included individuals with AN, included tests measuring setshifting and/or central coherence, investigated associations between set-shifting/central coherence withanxiety and/or depression and/or BMI. Risk of bias was assessed by using a critical appraisal checklist from theJoanna Briggs Institute. Results were summarized in a narrative synthesis.Results: Although results are heterogeneous, the majority of studies report that neither body mass index(BMI), anxiety or depression is associated with altered central coherence and set-shifting in individuals withAN.Conclusions: Findings indicate that BMI, depression and anxiety does not influence neuropsychologicalfunction in AN, suggesting that it could be a characteristic of the disorder. A complete understanding ofpredisposing, precipitating and maintaining factors in AN needs to be addressed in future research. This couldcontribute to the development of better and more targeted treatment strategies.Keywords: Anorexia nervosa, Set-shifting, Central coherence, Anxiety, Depression, Body mass index, SystematicreviewCorrespondence: Tone.Seim.Fuglset@helse-mr.noMøre and Romsdal Hospital Trust, Molde Hospital, Parkvegen 84, 6412 Molde,Norway The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.The Creative Commons Public Domain Dedication waiver ) applies to thedata made available in this article, unless otherwise stated in a credit line to the data.
Fuglset BMC Psychiatry(2021) 21:137BackgroundEating disorders are characterized by a persistent disturbance of eating or eating-related behaviour that result in altered consumption of food, whichsignificantly impairs physical health or psychosocialfunctioning [1]. Anorexia nervosa (AN) is a severeeating disorder, with the highest mortality rate of anymental illness [2]. It is recognized by a relentless pursuit for thinness, extreme low body weight, and isoften accompanied by a disturbed body image and adenial of illness. The aetiology of AN remains unclear, however the disorder is most likely caused by acomplex interaction between genetic and environmental factors. Genetic variants significantly associatedwith AN have recently been identified, which demonstrates that the origins of this disorder is both metabolic and psychiatric [3].Neuropsychological function in AN has been investigated in a number of studies, suggesting that specificneuropsychological impairments may be related to thepathophysiology of the disorder. These studies show thatindividuals with AN often display poor set-shifting abilities and weak central coherence (for systematic reviewssee [4, 5]). Set-shifting, or cognitive flexibility, refers tothe ability to shift thoughts or actions according to situational demands. Central coherence is the degree tofocus on details in processing information and the globalintegration of such information [6]. Individuals withweak central coherence have a preference for detailsover global processing. These findings are most commonly seen in adults, and findings from studies including adolescents are less consistent [7, 8]. It is worthnoting that adolescence is a time of considerable development of the brain and cognitive abilities, affecting thedevelopment of both executive functions and social cognition [9].Neuropsychological impairments in AN could be acharacteristic of the disorder, however, it could also be aconsequence of malnutrition and underweight. Yet, therole of starvation is still unclear, as some neuropsychological functions remains intact and general intelligence iswithin the normal range [10]. In fact, studies have shownthat patients with AN perform better on selected tasks,such as tasks requiring local information processing [5,11, 12]. A review and meta-analysis state that individualswith AN score above the average intelligence quotient ofthe normative population in the National Adult ReadingTest and Wechsler Intelligence Scales [13].Individuals with AN often suffer from comorbid mentaldisorders. The most common comorbidities are mood disorders, personality disorders, anxiety disorders, obsessivecompulsive disorders, and developmental disorders (e.g.autism spectrum, attention-deficit hyperactivity disorder)[14]. Both depression and anxiety have been linked toPage 2 of 14cognitive impairments in the domains of episodic memory, verbal memory as well as varying subsets of executivefunction [15, 16]. However, the role of depression andanxiety on neuropsychological performance in individualswith AN remains unclear. On one hand, comorbid psychiatric symptoms such as depression and anxiety may contribute to poorer performance on neuropsychologicaltasks. On the other hand, poorer performance could alsobe a characteristic of the disorder, and unrelated to noneating disorder psychopathology.A complete understanding of neuropsychological function in AN may contribute to the development of betterand more specific treatment strategies. It would be beneficial to determine whether neuropsychological impairments are related to comorbid disorders or as aconsequence of underweight, or whether these are morelikely a characteristic of the disorder per se. If so, thisshould be targeted in treatment.Set-shifting and central coherence are the most studied cognitive domains in individuals with AN. This systematic review provide an overview of relevant studiesand their findings concerning the relationship betweenclinical measures and neuropsychological function inAN. The aim of the current systematic review is toevaluate whether the observed alterations in set-shiftingand central coherence in patients with AN are influenced by body mass index (BMI), ED severity andbroader transdiagnostic factors such as anxiety anddepression.MethodsThis systematic review was guided by the PRISMA criteria [17].Eligibility criteriaAll primary studies were peer-reviewed and written inEnglish. There were no limitations in terms of timeframe. Studies were included if they met the followinginclusion criteria:1.2.3.4.Manuscript written in EnglishStudy published in peer-reviewed journalsIncluded individuals diagnosed with ANIncluded tests measuring set-shifting and/or centralcoherence5. Investigated associations between set-shifting/central coherence with anxiety and/or depression and/or BMISearch strategy and selection of studiesLiterature search was performed in PubMed, PsychInfo and Embase databases. A search for [anorexianervosa] AND [central coherence] resulted in 73(PubMed), 54 (PsychInfo) and 73 (Embase) articles. A
Fuglset BMC Psychiatry(2021) 21:137search for [anorexia nervosa] and [set shifting] resulted in 92 (Pubmed), 101 (PsychInfo) and 117(Embase) articles. See Additional file 1 for searchstrategy in PubMed. In total, the search resulted in510 articles. After the initial searches in the differentdatabases, duplicates were removed. Then, all titlesand abstracts of 189 articles were examined and evaluated for relevance, which resulted in removal of 76articles. Then, full text for all potential relevant articles (113), were obtained and screened thoroughly forrelevance. Seventy-two articles were then removeddue to lack of statistical analyses between neuropsychological function and clinical measures, or theywere not relevant for the current review. In all, atotal of 41 articles were included in the present study.Figure 1 illustrates a PRISMA flow chart of thesearch strategy (see Fig. 1).Fig. 1 PRISMA 2009 flow diagramPage 3 of 14Data extractionThe following variables were extracted from the articles:Authors, publication year, sample (size and diagnosis),neuropsychological test, measures of anxiety, depressionand eating disorder symptoms, cognitive domain (setshifting or central coherence), medical treatment. Outcome measures included analyses examining the relationship between set-shifting and/or central coherenceand depression/anxiety/BMI/weight for height/eatingdisorder symptoms.Assessment of risk of bias in included studiesRisk of bias of the included studies was assessed by usinga critical appraisal checklist for case control studies andcross sectional studies from the Joanna Briggs sal-tools), whichpurpose is to assess the methodological quality of a
Fuglset BMC Psychiatry(2021) 21:137study and to determine the extent to which a study hasaddressed the possibility of bias in its design, conductand analysis. See Additional files 2 and 3.Page 4 of 14not included in the table, as the majority of the studiesdid not report effect size measures of the association between neuropsychological function and clinicalmeasures.Data synthesisDue to the heterogeneity of the primary studies, especially considering the wide variety of neuropsychologicaltests and measures of psychopathology, and that different statistical methods have been used, a narrative synthesis approach was used for this current review.Study characteristicsSeven studies included an adolescent sample (age 18years) [18–24], and four studies included both adultsand adolescents [25–28]. The remaining 26 studies included an adult sample (age 18 years).A variety of tests were used to measure set-shifting:Haptic Illusion Task, Cognitive Shift Task, Trail MakingTest, Brixton Spatial Anticipation Test, Picture Set Test,Verbal Fluency Task, CatBat Task, Intra/Extra Dimensional Set Shift Test, Wisconsin Card Sorting Test, Visual Set-Shifting Task, Berg’s Card Sorting Test,Parametric Go/NoGo Test, Category Learning Task,Task Switching Paradigm, Design Fluency Task, CuedColor-Shape Switching Task and Comprehensive TrailMaking Test. The following tests were used to measurecentral coherence: Rey Complex Figure Test, EmbeddedFigures Test, Sentence Completion Task, HomographReading Task, Overlapping Figures Test, FragmentedPictures Task, Block Design, Object Assembly andGroup Embedded Figures Test.Different measures were used to assess anxiety and depression. The following measures were used to measureanxiety: State-Trait Anxiety Inventory (n 14), HospitalAnxiety and Depression Scale (n 8), Beck’s Anxiety inventory (n 1), Depression, Anxiety and Stress Scale(n 2), Spence Children’s Anxiety Scale (n 1) and BeckYouth Inventory (n 1). The most common measure ofdepression was Beck’s Depression Inventory (n 18),then HADS (n 8), Depression, Anxiety and Stress Scale(n 2), Hopkins Symptoms Checklist (n 1), Quick Inventory of Depressive Symptomatology, Children’s Depression Inventory (n 1) and German depressioninventory for children and adolescents (n 1).To examine the associations between cognitive performance and clinical characteristics, different regressionanalyses accounting for covariates as well as correlationanalyses, both Pearson and Spearman’s, were used.ResultsTable 1 summarises the studies in more detail, includingauthor, sample size (mean age), tests and significant correlations. The studies are organized chronologically according to year of publication. Measure of effect size isRisk of bias in included studiesThe majority of the studies included in the review had alow risk of bias, i.e. the groups were comparable otherthan the presence of disease, and the groups were properly matched. Valid, standardized tests were used, andtesting procedures were the same for all participants.Confounding variables were identified and controlledfor, and appropriate statistical tests were used. However,in some studies, issues concerning representativeness ofthe patient group and lacking control of possible confounding factors, led to an increased risk of bias. In onestudy, there was a low participation rate, which couldaffect the representativeness of the AN group [53]. Another study included a specific sample of AN with strictinclusion criteria, suggesting that this group was notrepresentative for the AN population [55]. One studyhad a very heterogeneous AN group in terms of differences in duration of illness, age of onset, treatment experience and different levels of illness severity [50].Furthermore, some of the studies did not control adequately for confounding factors. Most commonly wasnot considering the effect of pharmacological treatmenton test performance [18, 39, 54, 56, 57], and lack of controlling for intelligence quotient [35, 51]. Other potentialconfounding factors are comorbidity, which was notassessed and controlled for in several studies [44, 56,57]. These factors contribute to an increased risk of biasin these studies.Body mass index and neuropsychological functionThe studies that included associations between BMI andneuropsychological function show variable results. Themajority of studies (n 28) found no significant associations between set-shifting or central coherence and BMI[20, 22–24, 27–32, 34–36, 39–45, 48, 52–58]. Somestudies (n 7) found an association between BMI andneuropsychological function. One study found that BMIcorrelated with the number of errors in the HomographReading Task, a measure of central coherence [5]. Anegative correlation was detected between BMI and theFragmented Picture Task, but the correlation was notsignificant after correcting for multiple comparisons[26]. Another study found that significant low centralcoherence index became non-significant when adjustingfor nadir BMI [50]. Herbrich et al. [21] found a negativecorrelation between BMI and Group Embedded FiguresTest in the AN-binge/purge group. In addition, a negative correlation was found between BMI and Trail Making Test – 4 in the AN restrictive group. Studies
Fuglset BMC Psychiatry(2021) 21:137Page 5 of 14Table 1 Overview of associations between neuropsychological function and clinical measures in patients with AN. Significantassociations are highlighted in boldAuthorsSample TestN (meanage)AnxietyDepressionBMI/WfHED severityTchanturiaet al., 2002[29]AN 30(25.2)ANREC 16(30.0)HC 23(27.6)Haptic IllusionTask (SS)Cognitive ShiftTask (SS)Group differences in theHaptic Illusion Taskremained after covaryingfor anxiety. Groupdifferences in thecognitive shift taskdisappeared whencontrolling for anxiety.–N/AN/ATchanturiaet al., 2004[30]AN 34(26.7)BN 19(26.5)HC 35(24.8)Trail Making Test(SS)Brixton SpatialAnticipation Test(SS)Picture Set Test(SS)Verbal FluencyTask (SS)CatBat Task (SS)Haptic IllusionTask (SS)–––N/AHollidayet al., 2005[31]AN 47(26.3) ANsisters 47 (27.6)HC 47(26.5)Haptic IllusionTask (SS)Brixton SpatialAnticipation Test(SS)Trail Making Test(SS)CatBat Task (SS)Anxiety scores correlatedwith the Haptic IllusionTask.Depression scorescorrelated with theHaptic Illusion Task.–N/AFowleret al., 2006[20]AN 25(16.9)HC 25(17.6)Intra/ExtraDimensional SetShift Test (SS)–––N/ASteinglasset al., 2006[32, 33]AN 15(25.6)HC 11(24.0)Wisconsin CardSorting Test (SS)––––Lopez et al., AN 422008 [5](28.4)HC 42(26.3)Rey ComplexFigure Test (CC)EmbeddedFigures Test (CC)SentenceCompletion Task(CC)HomographReading Task(CC)––BMI correlated withnumber of errors in theinitial pronunciation inthe Homograph ReadingTask.N/AKim et al.,2010 [34]AN 40(22.8)BN 28(23.0)HC 34(22.7)Trail Making Test(SS)–Depression slightlycorrelated with setshifting.––Robertset al., 2010[35]AN 35(23.7)AN-BP 33 (25.6)BN 30(26.4)ANREC 30(32.1)Trail Making Test(SS)Wisconsin CardSorting Test (SS)Brixton SpatialAnticipation Test(SS)Haptic illusionTask (SS)Increased anxiety in thepoor set-shifting group,but effects were smallIncreased depression inthe poor set-shiftinggroup, but effects weresmall.–Those withpoor setshifting hadhigher scoreon the YBCEDS
Fuglset BMC Psychiatry(2021) 21:137Page 6 of 14Table 1 Overview of associations between neuropsychological function and clinical measures in patients with AN. Significantassociations are highlighted in bold (Continued)AuthorsSample TestN (meanage)AnxietyDepressionBMI/WfHED severity––ANsister 30 (24.2)BNsister 20 (27.6)HC 88(28.4)State anxiety had a–moderate correlation withTrail Making Test andOverlapping Figures Test.Tenconiet al., 2010[36]AN 153(26.2)HC 120(27.4)Wisconsin CardSorting Test (SS)Trail Making Test(SS)Rey ComplexFigure Test CC)OverlappingFigures Test (CC)Harrisonet al., 2011[26]AN 50(16–55)BN 48(16–55)ANREC 35(16–55)HC 89(16–55)Fragmented–Pictures Task (CC)Rey ComplexFigure Test (CC)GroupEmbeddedFigures Test (CC)–Negative correlationbetween BMI andFragmented Picture Task,but not significant aftercorrecting for multiplecomparisons.Those withreducedcentralcoherence hadhigher EDE-QGlobal scoreMcAnarneyet al., 2011[27]AN-R 24 (14–20)HC 37(14–20)Wisconsin CardSorting Test (SS)Intra/ExtradimensionalSet Shift test (SS)N/AN/ANo significant correlations.N/ABührenet al., 2012[37]AN 28(15.6)HC 27(15.0)Visual SetShifting Task (SS)––N/AN/ADanneret al., 2012[38]AN 16(25.6)ANREC 15(24.3)HC 15(25.8)Berg’s CardSorting Test (SS)Rey ComplexFigure Test (CC)A better copy accuracyon the Rey ComplexFigure Task was relatedto higher levels ofanxiety.–N/A–Galimbertiet al., 2012[39]AN-R 24 (26.7)AN-BP 12 (27.1)BN 16(25.3)HC 40(25.9)Intra/ExtradimensionalSet shift test (SS)–––N/AGiel et al.,2012 [40]AN 15(23.9)UD 20(36.3)HC 35(30.2)Trail Making Test(SS)Wisconsin CardSorting Test (SS)Parametric Go/No-Go Test (SS)N/ASignificant medium–correlations were foundin both AN and UDpatients.–Shott et al.,2012 [28]ADOLAN 15(14.8)ADOLC 16(14.0)CategoryLearning Task(SS)––––
Fuglset BMC Psychiatry(2021) 21:137Page 7 of 14Table 1 Overview of associations between neuropsychological function and clinical measures in patients with AN. Significantassociations are highlighted in bold (Continued)AuthorsSample TestN (meanage)AnxietyDepressionBMI/WfHED severityADULTAN 26(26.2)ADULT –C 33(26.0)Galimbertiet al., 2013[41]AN 29(24.1)HC 29(28.6)Wisconsin CardSorting Test (SS)N/AN/A––Tapajozet al., 2013[42]AN 24(24.5)BN 24(24.4)HC 24(25.2)Rey ComplexFigure Task (CC)––––VanAutreveet al., 2013[43]AN-R 31 (26.0)AN-BP 20 (20.0)HC 26(19.0)Block design (CC) Trait anxiety in the AN-BP –Object Assembly group correlated with Ob(CC)ject Assembly.Wisconsin CardSor
(n 2), Spence Children’s Anxiety Scale (n 1) and Beck Youth Inventory (n 1). The most common measure of depression was Beck’s Depression Inventory (n 18), then HADS (n 8), Depression, Anxiety and Stress Scale (n 2), Hopkins Symptoms Checklist (n 1), Quick In-ventory of Depressive Symptomatology, Children’s De- pression Inventory (n 1) and German depression inventory for children and .
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