An ecological approach to the behavioral assessment of executive functions in anorexia nervosa

Author’s Accepted Manuscript An Ecological Approach to the Behavioral Assessment of Executive Functions in Anorexia Nervosa Grazia Fernanda Spitoni, Massimiliano Aragonaa, Sara Bevacqua, Armando Cotugno, Gabriella Antonucci www.elsevier.com/locate/psychres

PII: DOI: Reference:

S0165-1781(17)30150-6 https://doi.org/10.1016/j.psychres.2017.10.029 PSY10929

To appear in: Psychiatry Research Received date: 26 January 2017 Revised date: 23 September 2017 Accepted date: 21 October 2017 Cite this article as: Grazia Fernanda Spitoni, Massimiliano Aragonaa, Sara Bevacqua, Armando Cotugno and Gabriella Antonucci, An Ecological Approach to the Behavioral Assessment of Executive Functions in Anorexia Nervosa, Psychiatry Research, https://doi.org/10.1016/j.psychres.2017.10.029 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

An Ecological Approach to the Behavioral Assessment of Executive Functions in Anorexia Nervosa

Grazia Fernanda Spitonia,b*, Massimiliano Aragonaac,d, Sara Bevacquaa, Armando Cotugnoe, Gabriella Antonuccia,b a

Department of Psychology–Sapienza University of Rome, Rome, Italy

b

Laboratory of Neuropsychology, IRCCS Santa Lucia Foundation, Rome, Italy

c

Crossing Dialogues Association, Rome, Italy

d

Day Hospital Disturbi del Comportamento Alimentare “Villa Armonia Nuova” ASL RMD, Rome,

Italy e

U.O.S.D. Disturbi del Comportamento Alimentare-Azienda Sanitaria Locale Roma E, Rome, Italy

*Corresponding author: Grazia Fernanda Spitoni: Via dei Marsi 78, 00185 Roma, +390644427877, [email protected]

Abstract The use of ecological tests to assess executive functions (EFs) in patients with anorexia nervosa (AN) has not examined extensively. The objective of this study was to analyze and compare the performance of patients with AN and healthy controls (HCs) on standard versus ecologically valid tests on EFs. Sixty-two females aged between 16 and 42 who were diagnosed with AN and 70 matched HCs completed 2 neuropsychological test batteries: standard tests (WCST, TMT, Stroop, ToL, fluency test) and the Behavioral Assessment of Dysexecutive Syndrome (BADS). On the standard tests, patients with AN produced more perseverative response and were slower than HCs 1

in the TMT; in contrast, they scored as well as HCs on tasks that assessed categorization, interference in color naming, planning and semantic fluency. Conversely, there were differences in the ecological tests with patients with AN systematically slower in the resolution of complex tasks. Results demonstrated the power of ecological tests in capturing selective impairments in multifaceted and unstructured tests. Patients with AN experienced systematic deceleration in the resolution of ecological tasks. Also, the increased time neede to solve the tasks, was not reflected in overall improvement in performance. This evidence is further discussed with respect to central coherence.

Keywords: neuropsychological assessment, eating disorders, ecological validity, speed of processing, central coherence

1. Introduction The neuropsychological profile of persons with anorexia nervosa (AN) has garnered considerable interest in the past several years. As demonstrated in the recent literature, AN has been associated with deficits in several cognitive domains, including verbal and visual learning, memory, visuospatial abilities (Oltra-Cucarella et al., 2014; Weider et al., 2015), and attention (Lauer et al., 1999). The most extensively studied neuropsychological abilities in AN have been executive control, executive functions (EFs) (Ciszewski et al., 2014; Ferraro et al., 2015; Garrido and Subira, 2013; Gillberg et al., 2010; Lezak, 2004; Lindner et al., 2012; Pignatti and Bernasconi, 2013; Tchanturia et al., 2014; Zakzanis et al., 2010), and detail-focused processing (i.e., central coherence) (Lopez et al., 2008; Stedal et al., 2012; Tenconi et al., 2010). Central coherence is a cognitive style in which there is a bias toward local or detailed focal processing of information over the natural tendency to integrate information in a contextual manner. Weak central coherence reflects a bias toward local or detail-oriented processing of information (Happé and Booth, 2008; 2

Happé and Frith, 2006). EFs refer to higher-order cognitive abilities that regulate and monitor most of our everyday actions. Neurodevelopmental studies have found that EFs are central in the predisposition to AN and the maintenance of its symptoms (Connan et al., 2003). In patients with AN, executive dysfunctions are characterized by deficits in decision-making, response inhibition, cognitive flexibility, and central coherence (Lena et al., 2005). Specifically, several groups have suggested that cognitive flexibility is generally impaired in patients who suffer from AN (Fagundo et al., 2012); for example, Yano and colleagues (2016) reported dysfunction of response inhibition on a task that assessed the interference effect. This finding was supported by Collantoni et al. (2016), who used the stop-signal paradigm to examine inhibitory control and the correlates of functional connectivity in a large sample of patients with AN. The authors noted impaired performance on the response inhibition task and disruption of functional connectivity of the ventral attention circuit, a neural network that has been implicated in behavioral responses when an unexpected stimulus occurs. A review by Zakzanis et al. (2010) indicated the need to address other complex EFs to better characterize the cognitive profiles in AN. For example, Carral-Fernàndez et al. (2016) examined a selective executive function in AN, termed “planning,” using 2 types of neuropsychological tasks to evaluate planning abilities: the Tower of London (TOL), a classic measure of planning abilities, and the Zoo Map test, a more ecologically valid planning measure that is part of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) (Wilson et al., 1997). This study showed that compared with matched controls, the AN group patients had similar results on the TOL, although they performed significantly worse in the Zoo Map Test. Carral-Fernàndez and colleagues (2016), concluded that, in women with AN, ecological measures might be better in the assessment of difficulties with indirect planning. Ecological validity has become an increasingly important factor in the neuropsychological assessment of EFs (Maïtè et al., 2016; McFadyen et al., 2015; Roy et al., 2015). Ecological validity 3

is the ability to generalize the results of controlled experiments to natural occurring events in everyday life. With regard to EFs, ecological validity can be described as the “functional and predictive relationship between the patient’s behavior on a set of neuropsychological tests and the patient’s behavior in a variety of real-world settings…” (Sbordone, 1996). Thus, an ecologically valid test has features that are similar to naturally occurring behaviors and has value in predicting everyday function (Franzen and Wilhelm, 1996). The use of ecological tests in psychiatry has risen in the past several years (e.g., Vizzotto et al., 2016; Farreny et al., 2013; Parada et al., 2012; Fernández-Serrano et al., 2010; Vargas et al., 2009), one of the main reasons for which appears to be their robust diagnostic sensitivity in assessing executive deficits in patients who perform normally on standard tests but still experience executive problems in everyday life (Chaytor and Schmitter-Edgecombe, 2003). Moreover, in evaluating eating disorders, clinicians frequently complain that patients continue to have serious executive problems in real-life situations, despite their unimpaired performance on standard tests. Thus, in the assessment of EFs in patients with AN, the ecological approach encompasses a wider range of executive dysfunctions. Accordingly, this study examined 1) whether “traditional and ecological tests are equally sensitive to executive dysfunction”2) whether ecological tests for EFs provide additional information in the neuropsychological assessment of AN.

2. Method

2.1. Participants 2.1.1. Patients Patients were recruited from 2 eating disorder departments in the Italian National Health Service for outpatient populations (UOSD Disturbi del Comportamento Alimentare- ASL Roma E and Villa Armonia Nuova- ASL Roma D). The research was explained to all patients in the units, and those 4

who were willing to participate scheduled a meeting with the researcher. Seventy-two patients were enrolled over 42 months, based on a sequential recruitment procedure. Following the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5, American Psychiatric Association, 2013) and a body mass index (BMI) < 18.5, the diagnosis of AN was defined by 2 psychiatrists with specific expertise and significant experience in the treatment of eating disorders; both psychiatrists are coauthors of this study. All patients had amenorrhea. The exclusion criteria were severe personality disorders, psychotic disorders, intellectual disability, general medical pathology that did not correlate with the eating disorder (e.g., neurological illness), and any substance or alcohol abuse or dependence during the previous year. Considering that personality disorders are frequent in AN (Martinussen et al., 2016), we used a conservative approach, excluding only patients with severe personality disorders. Personality disorders were qualified as being severe, based on 2 factors: type of disorder (schizoid, paranoid, schizotypal, antisocial, borderline) and low functioning in core domains of personality (Verheul et al., 2008)". Exclusion of neurological and major psychiatric disorders and substance dependence was clinically assessed based on the anamnesis and clinical examination (i.e. evaluation of the state of consciousness and mental state according to DSM-5 criteria, physical examination, neurological examination including pupillary reflex for possible drug use, etc.). Prior to study entry, the participants completed a preliminary semistructured diagnostic interview on eating disorder symptoms that was adapted for Italian use from the EDA-5 (Sysko et al., 2015). Also, to assess specific aspects of the psychopathology of EDs, we administered the Eating Disorders Inventory (EDI-2; Garner et al., 1983). Among the patients who entered the study, 8 did not complete the evaluation and were excluded from the analysis. The most frequent causes for the patients’ defeat were personal commitments and hospital scheduling system (rigorous timing slots for the use of the testing room). 5

The final sample consisted of 62 female participants, aged between 16 and 42 years. Mean disease duration was 46.69 months (range: 13–72). The BMI of the patients ranged between 10 and 18. Patients were all restricting type.

2.1.2. Healthy controls Healthy controls (HCs) (N=70 females) had no history of neurological or psychiatric disease, were in good health, and were not on any medication. They were recruited from the students and employee population of University of Rome, La Sapienza. The exclusion criteria for HCs were: presence of mental disorders, including any type of ED; BMI below 19; and any substance dependence in the past 24 months. The demographics of the patients and controls are shown in Table 1. This study was approved by the ethics committee of the Department of Psychology of La Sapienza, University of Rome and conformed to The Code of Ethics of the World Medical Association (Declaration of Helsinki), as printed in the British Medical Journal (July 18, 1964). All participants provided written informed consent. If a patient was a minor (underage), a parent had to give consent before the experimental session was begun.

2.2. Procedure All participants were evaluated in 3 separate sessions, with an interval of at least 2 days between meetings. In the first session, participants underwent a psychiatric interview and neuropsychological screen. In the second session, they were administered the traditional EFs tests, and on the last day, they underwent an ecological assessment of EFs. The order in which the tests were administered was

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balanced between participants; thus, 50% of participants received the traditional tests before the ecological measures, and the remaining 50% took the traditional tests after the ecological assessment. The HCs performed the same protocol.

2.2.1. Neuropsychological assessment The participants underwent a neuropsychological screen that comprised the following tests: orientation test, token test (De Renzi and Faglioni, 1978), digit span (Orsini and Laicardi, 1997; Wechsler, 1981), letter cancellation task for visual attention (Della Sala et al., 1992), the Standard Progressive Matrices (SPM38; Di Fabio and Clarotti, 2007; Raven, 1940), and the Wais-R Vocabulary (Orsini and Laicardi, 1997; Wechsler, 1981). Based on the literature on global processing difficulties and superior local processing in AN (Lindner et al., 2013; Lopez et al., 2008), we also assessed central coherence with the Rey-Osterrieth Complex Figure Test (ROCF) (Carlesimo et al., 2002; Osterrieth, 1944; Rey, 1941). Central coherence index (CCI) was measured using the Booth scoring system (Booth, 2006), as modified by Lopez et al. (2008). To examine the order in which participants drew the figure, we used the pen-switching method of Lezak (2004). The CCI is an objective measure of central coherence, and consists of an order of construction index and a style index; the former ranges from 0 to 3.3, the latter is scored from 0 to 2, and CCI ranges from 0 to 2. A higher CCI reflects a more coherent and global drawing style (e.g., the drawing begins from global elements and continues with fragmented details), whereas lower scores indicate a drawing style that focuses on details.

2.2.2. Traditional tests of executive function The examination comprised 6 standard tests: the Wisconsin Card Sorting Test (WCST) (Hardoy et al., 2000; Heaton et al., 1981), the Trail Making Test (TMT) (Giovagnoli et al., 1996; Reitan,

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1955), the Color-Word Interference, or Stroop Test (Caffarra et al., 2002; Stroop, 1935), Phonemic Verbal Fluency (Novelli et al., 1986), Semantic Verbal Fluency (Spinnler and Tognoni, 1987), and the Tower of London (Allamanno et al., 1982).

2.2.3. Ecological tests of executive function The ecological assessment of EFs was performed with the Behavioral Assessment of Dysexecutive Syndrome (BADS) (Wilson et al., 1997; Antonucci et al., 2014). The BADS is sensitive to the capacities that are required to solve executive demands, emphasizing those that are usually exercised in everyday situations. Also, the multifactorial nature of the BADS allows one to examine and compare several executive components (i.e., task switch, planning, problem solving, and control inhibition), permitting the clinician to design a multifactorial neuropsychological profile of executive dysfunctions. Normative data on an Italian sample of 1427 healthy participants aged 16 to 75 years and 74 traumatic injury patients showed high ecological validity, good concurrent validity and good test-retest reliability (see Antonucci et al., 2014). Moreover, the BADS has been used successfully for many diagnostic protocols in the neuropsychological (Barker et al., 2010; Motta et al., 2014; Santangelo et al., 2015; Uchikawa et al., 2014; Van der Hiele et al., 2012) and psychiatric domains (Farreny et al., 2013; Miyaguchi et al., 2012; Monica et al., 2010; Baba et al., 2010; Josman et al., 2009; Vargas et al., 2009; Moriyama et al., 2002). Thus, we decided to use the BADS as a first-choice battery for the ecological assessment of EFs in AN.

(See Tables 1S and 2S in Supplementary Section for a detailed description of all tests used in this study). 2.3. Data Analysis The data were processed using SPSS (IBM) and

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To analyze between-group differences in demographics and clinical variables, independent sample t-test was performed for age, BMI, education, and EDI-2 (total score). To examine the differences in CCI and EF measures between patients and controls, a series of general linear models (GLMs) were run with BMI as a covariate. In the first set of GLMs, ‘group’ (patients vs controls) was the between-subject factor, and CCI (Copy, Delay recall 30” and delay recall 20’) were the dependent variables. Similarly, in the second set of GLMs, ‘group’ (patients vs controls) was the between-subject factor, and traditional EF tests (WCST, TMT, Stroop, Fluency, TOL) were the dependent variables. In the final set of GLMs, ‘group’ (patients vs controls) was the between-subject factor, and ecological EF tests (Rule shift Card, Action Program, Key search, Temporal Judgments, Zoo Map 1, Zoo Map 2 and Six Elements) were the dependent variables. Given the existence of significant differences between groups, BMI was included as a covariate in all the GLM analyses. Partial eta-squared (ηp2) was calculated to quantify the effect sizes of all comparisons. Finally, to control for the power of the analyses for 2-group MANOVA, we run a post-hoc power analyses using G*power software.

3. Results

3.1 Neuropsychological assessment As reported in Table 2, patients with AN and HCs did not differ with regard to basic neuropsychological functions, indicating that cognitive profile was unimpaired with regard to orientation, comprehension and vocabulary, short-term memory, visual attention, and general visuospatial reasoning.

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3.2. Rey-Osterrieth Complex Figure- Central Coherence Index We did not observe any differences in CCI between groups in copying the Rey-Osterrieth figure. In contrast, the performance of patients differed significantly from that of controls with regard to the CCI of the delayed recall task after 30 seconds and 20 minutes (see Table 3).

3.3. Executive Functions As reported in Table 4, in the traditional EF tests, patients with AN scored similarly to HCs on 4 tasks: categorization (WCST number of categories), color naming (Stroop), planning (TOL), and semantic fluency. In contrast, patients with AN developed more perseverative responses in the WCST and were slower than HCs on part B of the TMT. Also, these patients performed better than HCs with regard to phonemic fluency. In the ecological tests (Table 5), the performance of patients with AN differed significantly from HCs for several executive tests: rule shift cards- time, key search- time, zoo map- accuracy, zoo map planning- time, and zoo map execution – time. In particular, patients with AN were systematically slower in the resolution of all tasks that required the execution time to be handled. Tables 4 and 5 compare the means in performance (Fisher F) between patients with AN and HCs on the traditional (Tab. 4) and ecological tests (Tab. 5). 3.4. Power of analyses Given a total sample size of 132, 2 groups (patients and controls), a critical F = 3.91, effect size = 0.25, α err prob. = 0.05 the post hoc power analysis for Fisher F generated a power (1-β err prob.) of 0.8135460.

4. Discussion This study examined traditional and ecological tests of EFs in a group of female patients with AN 10

and in HCs. Specifically, we compared the performance between groups on 5 traditional tests (the WCST, TMT, Stroop, TOL, and Fluency tests) and 6 ecological tests that were derived from the BADS. On the traditional EF tests, patients with AN scored similarly to HCs in 4 tasks: categorization (WCST number of categories), color naming (Stroop), planning (TOL), and semantic fluency. In contrast, they generated more perseverative responses on the WCST and were slower than HCs on part B of the TMT. Also, patients with AN performed better than HCs with regard to phonemic fluency. These results are consistent with the literature, which has shown the set-shifting deficits and superiority of patients with AN in phonemic fluency tasks (Stedal et al., 2012; Rose et al., 2011). On the ecological tests, the performance of patients with AN differed significantly from that of HCs for several executive tasks: rule shift cards- time; key search- time; zoo map- accuracy; zoo map planning- time; and zoo map execution- time. In particular, patients with AN were systematically slower then HCs.. These results suggest that in persons with AN, ecological tests are particularly sensitive in examining the processing speed in highly demanding executive tasks. This evidence supports previous findings of lower velocity in patients with AN on visuospatial and memory tasks (e.g., Oltra-Cucarella et al., 2014; 2015). Regarding the interference in the reaction times of people suffering from eating disorders on the Stroop test, Dobson and Dozois (2004) concluded that there was an attentional bias in the emotional-Food/Shape Stroop test, whereas they noted impaired patterns in the classic Stroop test. Simlarly, in a dimensional study on eating disorders, Fagundo and colleagues (2012) observed that the performance of patients with AN on the traditional Stroop test was not impaired. Our results on the Stroop test are consistent with these latter reports. Concerning planning abilities in AN, the TOL has been used as a measure of constructive planning in few studies. Recently, Carral Fernandez and colleagues (2016) observed that patients with AN performed as well as HCs on the TOL, which is consistent with our data, in which AN patients and HCs performed similarly on the TOL. On the TMT (part B), we found that patients were 11

significantly slower than controls, which is notable, because this result supports evidence of a specific slowdown in AN for highly demanding executive tasks. Whereas the performance of patients with AN and HCs on the traditional EF tests was generally comparable, our findings on new ecologically valid tests appear to be more coherent in detecting selective cognitive deficits in AN. In particular, patients with AN were systematically slower than HCs when the test resolution was less structured and more similar to everyday decisions and planning. The primary results on the Zoo Map Test are not completely consistent with a study on the same test in AN (Carral-Fernàndez et al., 2016). Our results contrast this report, likely because the variables in the analyses between studies differed. In Carral-Fernandez et al. (2016), the authors were interested solely in the planning abilities of the patients and thus used merely the part 1of the Zoo Map test; also, they focused only on two variables: planning time and sequencing score. Instead, we aimed to compare the ability of traditional and ecological tests to assess full executive profiles. For this reason, we administered the entire test (part 1 and part 2 and used all of the variables that contribute to a complete executive score on the Zoo Map Test (i.e., planning time, execution time, and accuracy). Finally, as opposed to Carral-Fernadez et al. (2016), who used British norms with the Spanish translation of the instructions, we used the Italian standardized version of the BADS (Antonucci et al., 2014). Collectively, these dissimilarities might explain the disparities between studies. One interpretation of the overall results centers on the cognitive theory of perfectionism in AN. As reported in early descriptions of this disorder (i.e., Bruch, 1978), perfectionism is considered a key cognitive mechanism in AN and has been studied extensively in more recent psychological literature (for a comprehensive review, see Bardone-Cone et al., 2007 and Boeren, 2013). We hypothesize that the increase in time that is needed by our patients to complete their tasks is a consequence of their basic cognitive perfectionism—i.e., the ecological EF tests in our study were 12

highly demanding tasks, with a risk of failure that could not be controlled for in advance. Confronted with this type of task and having high performance standards with exaggerated cognitive control and reduced flexibility (Friederich and Herzog, 2011), the patients might have slowed their execution to be as precise as possible. This interpretation is consistent with studies that have reported more checking and longer execution times using novel performance-based measures to assess perfectionism in AN (Lloyd et al., 2014). We obtained significant results on this performance style in the Rey-Osterrieth Figure test, on which the performance of patients with AN differed significantly from that of HCs with regard to the CCI of the delayed recall task after 30 seconds and 20 minutes. These differences indicate that patients with AN tend to focus more on the details of the object than on its general features. This evidence, which supports and confirms studies on central coherence in AN (for a recent review, see Lang et al., 2014), must be integrated with the findings above on the similar performance levels, which require more time than expected. There are several limitations of this study. In relation to Booth scoring system for CCI, it is important to remind that data are lacking and that future study should confirm the validity and reliability of the method. Also, we used only one ecological battery, which might have been insufficient to cover all possible everyday dysexecutive problems for patients with AN. Moreover, we did not analyze the potential interaction of psychopharmacological therapy with the main variables. Few patients (12 %) were taking antidepressants or low dosages of benzodiazepines to improve sleeping; thus, we did not expect to observe a significant influence of pharmacological therapy on the results. Also, we interpreted some of our results in relation to perfectionism. However, this interpretation is indirect, because we did not administer specific rating scales for perfectionism. Future studies should integrate rating scales on perfectionism, EF ecological tests, and other neuropsychological measures that can evaluate particular aspects of perfectionism. Because high levels of perfectionism are associated with cognitive distortions in body

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representation in AN (Spitoni et al., 2015), future studies should also consider the relationship between ecological EF data, specific aspects of perfectionism, and dissatisfaction with body representation. Finally, the particular nature of the variables that we used did not allowed us to analyzing the sensitivity and specificity of the ecological measures. Also, we did not collect data on performance validity; thus, caution should be taken before making any final conclusions. Our study is the first report to perform a complete ecological assessment of EF in the cognitive evaluation of AN, demonstrating consistent evidence of a systematic slowdown in the resolution of high demanding executive tasks. This novel evidence is consistent with the literature on central coherence that increased attention to detail is characteristic of AN (Lang et al., 2014) and that performance of participants with AN at the expense of increased time is attributed to striving for positive achievements but is motivated by perfectionistic attempts to avoid mistakes and by doubts over one’s performance (Lloyd et al., 2014). Overall, our findings suggest that AN is characterized by a basic cognitive tendency toward perseveration and detail orientation that negatively influences one’s performance, leading to unduly longer execution times that are devoid of significant advantages with regard to accuracy. These results can be interpreted in light of the perfectionistic model of AN, in which a fear of failure (with related doubts about actions, increased checking, and over-control) and an overemphasis on the supposed expectations of others cause one to spend more time than needed on focusing on details without experiencing consistent improvement in accuracy. In conclusion, our study shows that the assessment of EFs in patients with AN can benefit from the use of ecological instruments, in addition to standard tests.

The authors declare that they have no conflicts of interest with respect to their authorship or the publication of this article.

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Table 1. Demographics of patients and controls. AN patients (N = 62) Mean (SD) 28.1 (2.64) 15 (1.9) 12.24 (1.87) 46.69 (18.12)

Healthy controls (N = 70) Mean (SD) 27.3 (4.25) 22.8 (6.9) 13.1 (1.76) -

P-value

Age (years) n.s. BMI (body mass index) t = 6.6, p < 0.001 Education (years) n.s. Duration of illness (months) EDI-2 (total score) 97.54 (26.03) 30.9 (12.8) t = 6.24, p < 0.001 Mean (and SD) of descriptive variables: demographic characteristics per group (anorexic patients and healthy controls) and between-group differences (two-tailed t-test).

Table 2. Results: Neuropsychological assessment. AN patients Mean (SD)

Healthy t p-value Cohen's d Controls Mean (SD) Orientation normal range normal range na na na Comprehension 35.86 (9.06) 35.93 (4.98) -0.52 0.95 -0.01 Digit Span 7.6 (1.6) 7.47 (1.50) 0.46 0.64 0.12 Visual Attention 52.96 (2.87) 53.24 (1.3) -0.72 0.46 -0.12 Reasoning (SPM38) 32.45 (3.28) 31.46 (4.67) 1.39 0.16 0.24 Vocabulary (WAIS III) 64.02 (3.24) 63.97(3.67) 0.09 0.92 0.01 Mean (and SD) of neuropsychological test per group (AN patients and healthy control) and between-group differences (two-tailed t-test).

Table 3. Comparisons of means in performances of patients and controls in Central Coherence Index (Booth scoring system). 21

AN patients Mean (SD)

Healthy p-value* η2 F Controls Mean (SD) Copy 1.30 1.31 0.13 0.03 2.03 (0.68) (0.08) Delayed recall 1.37 1.61 0.13 19.5 0.00 30” (0.07) (0.15) Delayed recall 1.43 1.65 0.11 16.0 0.00 20’ (0.07) (0.15) The data of patients and controls were compared by GLM, with BMI as a covariate. *Bonferroni corrected.

Table 4. Comparisons of means in performance of patients and controls in the traditional measures of executive functions. Measures

AN patients Mean (SD)

Healthy controls Mean (SD)

η2

F P*

WCST number of categories

WCST perseverative responses

TMT time A

TMT time B

STROOP color naming

STROOP interference

FLUENCY Phonemic

FLUENCY Semantic

TOL accuracy

4.99 (1.07)

5.05 (1.12)

21.97 (4.84)

19.64 (4.83)

46.76 (7.35)

45.06 (10.111)

99.58 (6.48)

75.36 (17.026)

101.27 (5.84)

102.64 (9.28)

326.32 (18.37)

326.32 (18.84)

39.95 (6.03)

35.20 (8.76)

21.58 (4.70)

21.93 (4.56)

31.42 (4.59)

31.9 (4.54)

0.00 0.62

0.43 0.03

5.04

0.02 0.01

1.41

0.23 0.10

15.45

0.00 0.00

0.00

0.94 0.00

0.84

0.77 0.01

1.30

0.25 0.03

4.76

0.31 0.00

0.06

0.79

Note: WCST=Wisconsin Card Sorting Test; TMT=Trial Making Test; TOL=Tower of London The data of patients and controls were compared by GLM, with BMI as a covariate. *Bonferroni corrected

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Table 5. Comparisons of means in performance of patients and controls in the ecological measures of executive functions AN patients

F

p*

η2

Healthy controls

Measures Mean (SD)

Mean (SD) Rule shift cards - accuracy

Rule shift cards - time

Action Program - accuracy

Key Search - accuracy

Key Search - Time

Temporal Judgments - accuracy

Zoo Map 1 – accuracy

Zoo Map 1 Planning - time

18.95 (1.03)

19.06 (1.04)

39.81 (7.22)

30.34 (6.14)

4.02 (1.10)

4.19 (1.06)

12.13 (1.07)

11.93 (1.26)

39.19 (1.05)

26.78 (1.19)

4.00

4.00

14.48 (0.53)

14.21 (0.75)

151.98

100.74 (12.7)

(39.056) Zoo Map 1 Execution - time

Zoo Map 2 - accuracy

Zoo Map 2 Planning - time

Zoo Map 2 Execution - time

Six Elements - accuracy

44.81 (6.41)

32.96 (4.33)

13.87 (0.58)

13.97 (0.16)

17 (11.54)

13.07 (12.93)

49.16 (31.80)

47.58 (22.39)

5.19 (1.05)

4.94 (1.38)

0.00 0.92

0.33 0.14

20.91

0.00 0.00

1.20

0.27 0.00

0.00

0.99 0.83

653.67

0.00

na

na 0.86

807.33

0.00 0.18

29.37

0.00 0.12

18.66

0.00 0.01

2.47

0.08 0.02

3.37

0.06 0.01

2.12

0.14 0.01

2.09

0.15

The data of patients and controls were compared by GLM, with BMI as a covariate. *Bonferroni corrected

23

Highlights     

Executive Functions assessment in Anorexia Nervosa Ecological tests compare to standard/classic neuropsychological measures Ecological assessment captures a selective cognitive impairment in Anorexia Nervosa Anorexic patients are significantly slower then controls in complex executive task The slow down is not consistently compensated by an improvement in performance

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