nutrients Article Lifetime Weight Course as a Phenotypic Marker of Severity and Therapeutic Response in Patients with Eating Disorders Zaida Agüera 1,2,3,4, * , Cristina Vintró-Alcaraz 1,2,3 , Isabel Baenas 1,2,3 , Roser Granero 1,5 , Isabel Sánchez 1,2 , Jéssica Sánchez-González 2 , José M. Menchón 2,3,6,7 , Susana Jiménez-Murcia 1,2,3,6 , Janet Treasure 8 and Fernando Fernández-Aranda 1,2,3,6, * 1 Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 08907 L’Hospitalet de Llobregat, Spain; cvintro@bellvitgehospital.cat (C.V.-A.); ibaenas@bellvitgehospital.cat (I.B.); Roser.Granero@uab.cat (R.G.); isasanchez@bellvitgehospital.cat (I.S.); sjimenez@bellvitgehospital.cat (S.J.-M.) 2 Department of Psychiatry, University Hospital of Bellvitge, 08907 L’Hospitalet de Llobregat, Spain; jsanchezg@bellvitgehospital.cat (J.S.-G.); jmenchon@bellvitgehospital.cat (J.M.M.) 3 Psychiatry and Mental Health Group, Neuroscience Program, Institut d’Investigació Biomèdica de Bellvitge—IDIBELL, 08907 L’Hospitalet de Llobregat, Spain 4 Department of Public Health, Mental Health and Maternal-Child Nursing, School of Nursing, University of Barcelona, 08907 L’Hospitalet de Llobregat, Spain 5 Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain 6 Department of Clinical Sciences, School of Medicine and Health Sciences, University of Barcelona,  08907 L’Hospitalet de Llobregat, Spain  7 Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Citation: Agüera, Z.; Vintró-Alcaraz, 08907 L’Hospitalet de Llobregat, Spain 8 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, C.; Baenas, I.; Granero, R.; Sánchez, I.; King’s College London, London WC2R 2LS, UK; janet.treasure@kcl.ac.uk Sánchez-González, J.; Menchón, J.M.; * Correspondence: zaguera@bellvitgehospital.cat (Z.A.); ffernandez@bellvitgehospital.cat (F.F.-A.); Jiménez-Murcia, S.; Treasure, J.; Tel.: +34-260-7227 (Z.A. & F.F.-A.) Fernández-Aranda, F. Lifetime Weight Course as a Phenotypic Abstract: The association between lifetime weight fluctuations and clinical characteristics has been Marker of Severity and Therapeutic Response in Patients with Eating widely studied in populations with eating disorders (ED). However, there is a lack of literature Disorders. Nutrients 2021, 13, 2034. examining the potential role of weight course as a transdiagnostic factor in ED so far. Therefore, the https://doi.org/10.3390/nu13062034 aim of this study is to compare ED severity and treatment outcomes among four specific BMI profiles based on BMI-trajectories across the lifespan: (a) persistent obesity (OB-OB; (n = 74)), (b) obesity in Academic Editor: Lidia Santarpia the past but currently in a normal weight range (OB-NW; n = 156), (c) normal weight throughout the lifespan (NW-NW; n = 756), and (d) current obesity but previously at normal weight (NW-OB; Received: 29 April 2021 n = 314). Lifetime obesity is associated with greater general psychopathology and personality traits Accepted: 10 June 2021 such as low persistence and self-directedness, and high reward dependence. Additionally, greater Published: 13 June 2021 extreme weight changes (NW-OB and OB-NW) were associated with higher psychopathology but not with greater ED severity. Higher dropout rates were found in the OB-OB group. These results Publisher’s Note: MDPI stays neutral shed new light on the BMI trajectory as a transdiagnostic feature playing a pivotal role in the severity with regard to jurisdictional claims in and treatment outcome in patients with ED. published maps and institutional affil- iations. Keywords: body mass index (BMI) profiles; eating disorders; obesity; treatment outcome Copyright: © 2021 by the authors. 1. Introduction Licensee MDPI, Basel, Switzerland. This article is an open access article Eating disorders (ED) and obesity have frequently been considered as part of the same distributed under the terms and continuum of so-called extreme weight conditions [1–3]. This continuum is reinforced conditions of the Creative Commons because both pathologies share risk and maintenance factors that have been widely de- Attribution (CC BY) license (https:// scribed in the literature [4–6]. Furthermore, genetic factors underlying body mass index creativecommons.org/licenses/by/ (BMI) have been associated with disordered eating behaviors and related cognitions, and 4.0/). these associations have also been mediated by BMI [7]. Among the different ED listed Nutrients 2021, 13, 2034. https://doi.org/10.3390/nu13062034 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, 2034 2 of 15 in the DSM-5 [8], binge eating disorder (BED) is the one with the highest prevalence of comorbid obesity [9,10] followed by bulimia nervosa (BN) [11]. Villarejo et al. [11] found that almost 30% of female patients with ED had lifetime obesity, and those patients were characterized by later age of onset, longer duration of the disorder, higher minimum and maximum-ever BMI, and higher eating-related and general psychopathological severity. Similarly, a continuum of severity has been described in which patients with obesity and BN show the highest symptomatology and psychopathology, followed by BED with obesity, with obesity without ED being the least severe [12]. The personality profiles of individuals with overweight or obesity have been widely reported in the literature, both in patients with [13,14] and without ED [15]. Patients with ED and lifetime obesity often present personality profiles characterized by a higher harm avoidance and lower scores in persistence, self-directedness, and cooperativeness than ED patients without obesity [11,12]. In addition, a systematic review on personality traits in obesity identified that high scores on reward sensitivity, impulsivity, and neuroticism may act as risk factors, whereas high self-directedness, persistence, and self-control would act as protective factors [15]. Weight trajectories [16] and fluctuations [17,18] have also been associated with disor- dered eating behaviors and may be of relevance as risk and maintaining factors [17,18]. Frequent weight fluctuations suggest some degree of dysregulation of weight homeosta- sis [19]. The difference between the premorbid weight before the onset of ED and current weight has been described as a risk factor for bulimic psychopathology [18,20]. It also appears as a predictor of weight gain during therapy [20,21] and poorer treatment out- comes [22]. Striegel-Moore et al. [23] found a rapid increase in weight trajectory two years prior to the onset of BED. Ivezaj et al. [24] also found that patients with BED and obesity reported a significant weight gain during the year before seeking treatment and this was associated with higher relapse rates, greater ED and affective psychopathology [24–26]. Furthermore, a large body of research has revealed that some ED-related characteristics such as emotional eating, binge eating behaviors, poor body image, and high body dis- satisfaction are associated with weight fluctuations in patients with ED [27,28]. Indeed, some authors have described above-average weights and more fluctuation in adolescents prior to the onset of the ED (i.e.,) [29]. Likewise, severe weight cycling was more prevalent among adult women with obesity and was associated with higher reward sensitivity, and depressive-related symptomatology, and a higher prevalence of BED [30]. The relationship between weight suppression (WS) (defined as the difference between the highest adult weight and the current weight) and ED has also been the subject of interest in the literature. However, it is difficult to draw firm conclusions as the evidence is mixed. Some studies found no associations between WS and clinical variables [31,32], whereas others found that WS was related to more severe ED symptomatology, greater depression, poorer prognosis, and greater weight gain at post treatment [17,33–35]. To our knowledge, no study has examined groups of patients with ED based on lifetime weight trajectories. Therefore, the main goal of the present study was to examine whether obesity across the lifespan might be a transdiagnostic marker of ED severity and treatment outcome. A clinical sample of people with ED was post hoc distributed into four BMI profiles according to the period of obesity over adulthood: (a) with lifespan obesity (OB-OB), (b) with past obesity but currently normal weight (OB-NW), (c) with normal weight throughout their lifespan (NW-NW), and (d) with previous normal weight but current obesity (NW-OB). Therefore, two substudies were conducted. The first cross- sectional substudy aimed (1) to examine whether the different diagnostic categories of EDs are differentially distributed across the BMI profiles and (2) to compare the BMI profiles in terms of motivational stage, ED severity, general psychopathology, personality traits, and impulsive behaviors. The aim of the second prospective substudy was to examine whether the BMI profile predicted treatment outcome. We hypothesized that the prevalence of patients with BED would be greater in BMI profiles with obesity. A second hypothesis was that patients with increased lifetime weight Nutrients 2021, 13, 2034 3 of 15 changes (i.e., OB-NW and NW-OB) would exhibit greater ED symptomatological and psychopathological severity, as a worse treatment outcome. 2. Materials and Methods 2.1. Participants The clinical sample consisted of 1300 adult patients with ED. All the patients were consecutive referrals for assessment and treatment to the EDs Unit, Department of Psychi- atry at the Bellvitge University Hospital (Barcelona, Spain). The sample was composed of 82 males and 1218 females meeting the criteria for BN (n = 719), BED (n = 211), and OSFED (n = 370). Patients admitted before 2013 were originally diagnosed according to DSM-IV-TR criteria [36]. All diagnoses were recoded post hoc using DSM-5 criteria [8]. The longitudinal substudy was conducted with 500 of the patients from the first substudy (91.6% females; 8.4% males) with available post-treatment data. Although differences were observed between the participants included and those not included in the longitudinal substudy in terms of diagnosis, sex, educational level, and employment status, it should be noted that they did not show significant differences in terms of the main clinical variables such as group distribution, age, age of onset of the ED, and symptomatological ED severity (see Supplementary Table S1). The following exclusion criteria were applied to both substudies: (a) age below 18 years old; (b) having a diagnosis of AN or presenting with a BMI below 18.5 kg/m2 ; (c) currently overweight (BMI: 25–29.9 kg/m2 ). The last two exclusion criteria were made according to a clinical consensus to suit the standardized definitions of normal weight and obesity and to cluster the empirical groups accordingly. Figure S1 (Supplementary Materials) includes the flowchart with the sampling procedure. Additional analyses confirmed that there was no methodological bias since there were no significant differences between included and nonincluded participants in the distribution of the main variables such as sociodemographic variables (sex: p = 0.065, education level: p = 0.127, marital status: p = 0.288, and age: p = 0.074), age of onset of the disorder (p = 0.986), and psychopathological severity (SCL-90R PST: p = 0.074, SCL-90R GSI: p = 0.075, and SCL-90R PSDI: p = 0.074). 2.2. Assessment Sociodemographic and clinical data were obtained by means of a face-to-face semistruc- tured interview based on the SCID-5 [37] administered by clinical psychologists and psy- chiatrists specialized in ED. During this clinical interview, data on the presence of certain impulsive behaviors, such as nonsuicidal self-injury (NSSI) behaviors, suicidal ideation and/or attempts, alcohol abuse, and drug abuse were also retrieved from specific questions that have been previously used in previous research [38,39]. The evolution of weight was recorded by asking about the minimum and maximum weight attained throughout adulthood and at what age they reached this weight, as well as the current weight at the time of assessment. Additionally, the following commonly applied questionnaires in the field of ED were administered: The Eating Disorder Inventory-2 (EDI-2) [40] is a 91-item self-reported questionnaire that assesses 11 ED-related cognitive and behavioral domains. A total score is also pro- vided to report overall ED severity. This instrument has been validated in a Spanish population [41]. In the current sample, the internal consistency was excellent (α = 0.948). The Symptom Checklist-90-Revised (SCL-90-R) [42] contains 90 items that measure 9 primary psychopathological dimensions: somatization, obsession–compulsion, inter- personal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism; and includes three global indices: global severity index (overall psychologi- cal distress), positive symptom distress index (the intensity of symptoms), and a positive symptom total (self-reported symptoms). This scale has been validated in a Spanish population [43]. In the present study, internal consistency was excellent (α = 0.976). The Temperament and Character Inventory-Revised (TCI-R) [44] is a 240-item self- reported questionnaire that measures seven dimensions of personality: four temperament Nutrients 2021, 13, 2034 4 of 15 dimensions (harm avoidance, novelty seeking, reward dependence, and persistence) and three character dimensions (self-directedness, cooperativeness, and self-transcendence). The Spanish validation was carried out by Gutierrez-Zotes et al. [45]. Our internal consis- tency ranged from α = 0.797 to α = 0.893. The motivation stage of change was evaluated by means of a visual analog scale, ranging from 0 to 8, which assessed the following five aspects: (1) subjective desire to receive treatment, (2) need for treatment, (3) perceived impairment, (4) self-concern, and (5) parental concern. Higher scores indicated greater worry and motivation to change. This scale has been previously described and applied in other studies [46]. 2.3. Treatment Treatment consisted of 16 weekly group outpatient sessions of cognitive behavioral therapy (CBT). There was a total of 8–10 patients per group. Although patients with BN, BED, and OSFED were placed in separate groups of therapy, all the treatment groups were based on the same CBT program. This program and its complementary material have already been manualized and published in Spanish [47] with demonstrated effective- ness [48–51]. Patients were reevaluated at discharge and categorized into the following DSM-5 categories [8]: full remission (total absence of symptoms meeting diagnostic criteria for at least 4 consecutive weeks), partial remission (substantial symptomatic improvement but with residual symptoms), and nonremission (poor outcome or exacerbation of symptoms). These categories were used to assess treatment outcomes in previously published stud- ies [48,50,52–54]. Voluntary treatment discontinuation was categorized as dropout (i.e., not attending treatment for at least three consecutive sessions). In accordance with the Declaration of Helsinki, the present study was approved by the Ethics Committee of our institution (The Clinical Research Ethics Committee (CEIC) of the Bellvitge University Hospital). All participants provided signed informed consent. 2.4. Statistical Analyses Statistical analysis was carried out with Stata16 (StataCorp, College Station, TX, USA) LLC for windows [55]. The comparison between the four groups of the study (OB-OB, OB-NW, NW-NW, and NW-OB) was based on chi-square tests (χ2 ) for categorical variables and analysis of variance (ANOVA) for quantitative variables. The effect size for the difference between means was estimated through the stan- dardized Cohen’s d coefficient, considering null effect size for |d| < 0.20, low-poor for |d| > 0.20, moderate-medium for |d| > 0.50, and large-high effect for |d| > 0.80) [56]. The effect size for the difference between proportions was estimated through the standardized Cohen’s h coefficient, which is interpreted similarly to Cohen’s d measure and calculated through the arcsine transformation of the rates registered in each group (null effect size is considered for |h| < 0.20, low-poor for |h| > 0.20, moderate-medium for |h| > 0.50, and large-high for |h| > 0.80) [57]. An increase in Type-I error due to multiple significance tests was controlled with the Finner method [58], a family-wise error rate (FWER) stepwise procedure, which has proved more powerful than the classical Bonferroni correction. When controlling the k-FWER, a fixed number of k-1 of erroneous rejections is tolerated, and under the assumption that all the null hypotheses are equal, controlling the FWER at level α is equivalent to the problem of combining the original-unadjusted p-values to obtain single testing for the null hypothesis (H0 ), which is at level α. For example, from a procedure R that controls the FWER at level α is equivalent to derive a single testing procedure of level α by rejecting the H0 whenever R(p) is not empty (that is, whenever R(p) rejects at least one hypothesis). In practice, the Finner method is employed by adjusting the rejection criteria for each of the individual hypotheses fixing the FWER no higher than a certain prespecified significance level. The procedure starts sorting the p(unadjusted)-values (p1, . . . , pk), achieved in k-independent null-hypothesis tests, into the order of lowest to highest. Then, the next the H0 whenever R(p) is not empty (that is, whenever R(p) rejects at least one hypothesis). In practice, the Finner method is employed by adjusting the rejection criteria for each of Nutrients 2021, 13, 2034 5 of 15 the individual hypotheses fixing the FWER no higher than a certain prespecified signifi- cance level. The procedure starts sorting the p(unadjusted)-values (p1, …, pk), achieved in k-independent null-hypothesis tests, into the order of lowest to highest. Then, the next algorithm algorithm isis used: used: p(adjusted) p(adjusted)==(1(1− − (1-p(unadjusted))^(total tests/position (1-p(unadjusted))ˆ(total within tests/position the the within or- dered tests). ordered tests). 3. Results 3.1. Comparison 3.1. Comparison between between the the Groups Groups for for Sociodemographics, Sociodemographics, BMI, BMI, and and Motivational Motivational Measures Measures Figure 11displays Figure displaysthe thediagnostic diagnostic profile profile within within eacheach grouping. grouping. The block The first first block of Tableof Table 1 includes cluster, sociodemographic and diagnostic information type. 1 includes cluster, sociodemographic and diagnostic information type. The OB-OB BMIThe OB-OB BMI profile profile included included mainly mainly patients patients with BED, with BED, whereas whereas patients patients withand with BN BNOSFED and OSFED diag- diagnoses were within the OB-NW and NW-NW groups. The fourth noses were within the OB-NW and NW-NW groups. The fourth BMI profile (i.e., BMI profile (i.e., NW-OB) NW-OB) consisted mainly of the BN and BED diagnostic consisted mainly of the BN and BED diagnostic types. types. 100% 5.4% 12.2% 90% 80% 36.5% 38.0% Diagnosis 70% 49.0% 0.0% 1.2% OSFED 60% 64.9% BED 50% BN 40% 30% 63.5% 60.8% 20% 45.5% 10% 23.0% 0% OB-OB OB-NW NW-NW NW-OB Figure 1. Distribution of the diagnostic subtype within the lifetime BMI profiles. Note: OB: obesity; normalweight; NW: normal weight;BN: BN:bulimia bulimia nervosa; nervosa; BED: BED: binge binge eating eating disorder; disorder; OSFED: OSFED: otherother specified specified feed- ing or eating feeding disorder. or eating disorder. The group with the highest prevalence of men was OB-NW, followed by OB-OB and NW-OB, only a small percentage of NW-NW patients were men. Higher levels of educational achievement were attained in the NW-NW and NW-OB groups. A higher proportion of the NW-OB patients were married. Those in the OB-OB group were more often employed, and those in the NW-NW more often studying. The NW-OB and OB-OB groups considered themselves to be most symptomatic and in need of treatment. Family members of NW-NW and OB-NW groups expressed most concern. 3.2. Comparison between the Groups for Clinical Measures Table 2 contains the comparison between the groups for the clinical profiles. People in the NW-NW group were younger, with an earlier age of onset and shorter duration of the disorder. Those in the NW-OB group were older, with a later age of onset and longer duration. The highest frequency of binges was noted within the NW-OB group, while the highest frequency of vomiting was noted in the OB-NW group. The OB-OB group had the lowest number of binges and vomiting episodes. The highest eating psychopathology (EDI-2 total score) was in the OB-OB group, followed by NW-OB, OB-NW, and NW-NW groups. The most severe general psychopatho- logical state (SCL-90R scores) was related to NW-OB, followed by OB-NW. The OB-OB group had higher levels of harm avoidance, reward dependence, coop- erativeness, and self-transcendence. The NW-NW group had higher levels of novelty seeking, persistence, and cooperativeness. The OB-NW group had lower levels of novelty seeking, reward dependence, and cooperativeness. The NW-OB group had higher levels of harm avoidance. Nutrients 2021, 13, 2034 6 of 15 Table 1. Comparison between the BMI profiles on sociodemographics, clinical, and motivational measures. OB-OB OB-NW NW-NW NW-OB OB-OB OB-OB OB-OB OB-NW OB-NW NW-NW n = 74 n = 156 n = 756 n = 314 vs OB-NW vs NW-NW vs NW-OB vs NW-NW vs NW-OB vs NW-OB n % n % n % n % p |h| p |h| p |h| p |h| p |h| p |h| Diagnosis BN 17 23.0% 99 63.5% 460 60.8% 143 45.5% <0.001 0.90 † <0.001 0.83 † 0.001 0.52 † 0.355 0.05 <0.001 0.37 <0.001 0.31 BED 48 64.9% 0 0.0% 9 1.2% 154 49.0% 1.92 † 1.84 † 0.32 0.16 1.39 † 1.32 † OSFED 9 12.2% 57 36.5% 287 38.0% 17 5.4% 0.59 † 0.62 † 0.24 0.03 0.83 † 0.86 † Gender Female 64 86.5% 124 79.5% 734 97.1% 296 94.3% 0.199 0.19 <0.001 0.39 0.020 0.27 <0.001 0.57 † <0.001 0.45 0.027 0.14 Male 10 13.5% 32 20.5% 22 2.9% 18 5.7% Education 42 56.8% 89 57.1% 294 38.9% 156 49.7% 0.969 0.01 0.009 0.36 0.209 0.14 <0.001 0.37 0.041 0.15 0.002 0.22 Primary Secondary 26 35.1% 53 34.0% 344 45.5% 108 34.4% 0.02 0.21 0.02 0.24 0.01 0.23 University 6 8.1% 14 9.0% 118 15.6% 50 15.9% 0.03 0.23 0.24 0.20 0.21 0.01 Civil status Single 42 56.8% 111 71.2% 654 86.5% 125 39.8% 0.003 * 0.30 <0.001 0.70 † 0.026 0.34 <0.001 0.38 <0.001 0.66 † <0.001 1.11 † Partner 27 36.5% 26 16.7% 68 9.0% 151 48.1% 0.51 † 0.69 † 0.24 0.23 0.71 † 0.96 † separated 5 6.8% 19 12.2% 34 4.5% 38 12.1% 0.19 0.10 0.18 0.28 0.00 0.28 Unemployed 25 33.8% 63 40.4% 202 26.7% 160 51.0% 0.341 0.14 <0.001 0.15 <0.001 0.35 <0.001 0.29 <0.001 0.21 <0.001 0.51 † Student 18 24.3% 43 27.6% 385 50.9% 24 7.6% 0.07 0.57 † 0.51 † 0.52 † 0.54 † 1.08 † Employed 31 41.9% 50 32.1% 169 22.4% 130 41.4% 0.20 0.43 0.01 0.22 0.19 0.42 BMI measures Mean SD Mean SD Mean SD Mean SD p |d| p |d| p |d| p |d| p |d| p |d| BMI current 44.95 9.46 22.16 1.74 20.81 1.66 36.54 5.25 <0.001 3.35 † <0.001 3.55 † <0.001 1.10 † <0.001 0.80 † <0.001 3.67 † <0.001 4.04 † BMI max. 48.45 9.50 34.72 4.94 22.76 1.43 38.48 5.79 <0.001 1.81 † <0.001 3.78 † <0.001 1.27 † <0.001 3.29 † <0.001 0.70 † <0.001 3.73 † BMI min. 33.41 3.17 19.92 2.55 17.99 1.88 21.89 2.17 <0.001 4.69 † <0.001 5.92 † <0.001 4.24 † <0.001 0.86 † <0.001 0.83 † <0.001 1.92 † Motivation: Intensity 6.14 1.62 5.64 2.17 5.12 1.97 6.24 1.75 0.069 0.26 <0.001 0.56 † 0.667 0.06 0.002 0.25 0.001 0.31 <0.001 0.60 † Need treatment 6.74 1.48 5.87 2.28 5.71 2.18 6.74 1.66 0.003 0.52 † <0.001 0.56 † 0.987 0.00 0.361 0.07 <0.001 0.44 <0.001 0.53 † Social 5.18 2.56 4.90 2.55 4.69 2.36 5.32 2.36 0.410 0.11 0.099 0.20 0.630 0.06 0.335 0.08 0.069 0.17 <0.001 0.27 impairment Self-concern 7.00 1.09 6.15 2.18 6.13 2.14 6.96 1.59 0.003 0.51 † <0.001 0.51 † 0.881 0.03 0.871 0.01 <0.001 0.42 <0.001 0.44 Family concern 6.09 2.32 6.57 2.09 6.68 2.00 5.95 2.36 0.112 0.22 0.023 0.27 0.595 0.06 0.553 0.05 0.003 0.28 <0.001 0.33 Note: OB: obesity; NW: normal weight; BN: bulimia nervosa; BED: binge eating disorder; OSFED: other specified feeding and eating disorder; SD: standard deviation; * bold: significant comparison; † bold: effect size into the range mild/moderate (|d| > 0.50 or |h| > 0.50) to large/high (|d| > 0.80 or |h| > 0.80). Nutrients 2021, 13, 2034 7 of 15 Table 2. Comparison between the groups for the clinical profile. OB-OB OB-NW NW-NW NW-OB OB-OB OB-OB OB-OB OB-NW OB-NW NW-NW n = 74 n = 156 n = 756 n = 314 vs OB-NW vs NW-NW vs NW-OB vs NW-NW vs NW-OB vs NW-OB Mean SD Mean SD Mean SD Mean SD p |d| p |d| p |d| p |d| p |d| p |d| Age (years-old) 32.70 10.56 29.12 9.01 24.91 7.60 37.61 10.77 0.004 * 0.36 0.001 * 0.85 † 0.001 * 0.51 † 0.001 * 0.51 † 0.001 * 0.86 † 0.001 * 1.36 † Onset of ED 19.91 8.84 20.88 8.74 17.76 4.88 25.28 10.82 0.356 0.11 0.018 0.30 0.001 * 0.54 † 0.001 * 0.44 0.001 * 0.45 0.001 * 0.90 † Duration of ED 12.80 8.62 8.27 7.21 7.19 6.95 12.41 10.01 0.001 * 0.57 † 0.001 * 0.72 † 0.708 0.04 0.122 0.15 0.001 * 0.51 † 0.001 * 0.61 † Binges/week 3.98 4.94 3.97 6.13 4.11 5.77 6.16 5.59 0.988 0.00 0.850 0.02 0.003 * 0.41 0.775 0.02 0.001 * 0.37 0.001 * 0.36 Vomits/week 1.63 4.67 7.04 9.40 5.16 7.38 2.46 6.14 0.001 * 0.73 † 0.001 * 0.57 † 0.376 0.15 0.003 * 0.22 0.001 * 0.58 † 0.001 * 0.40 EDI-2: Total 113.26 38.67 109.56 45.35 100.72 40.28 111.45 38.26 0.517 0.09 0.011 * 0.32 0.729 0.05 0.013 0.21 0.633 0.05 0.001 * 0.27 score SCL-90R GSI 1.73 0.73 1.87 0.75 1.72 0.70 1.91 0.73 0.161 0.19 0.875 0.02 0.059 0.24 0.014 * 0.21 0.638 0.04 0.001 * 0.26 SCL-90R PST 62.12 16.26 65.42 18.65 64.78 17.00 66.32 15.82 0.167 0.19 0.196 0.16 0.054 0.26 0.669 0.04 0.583 0.05 0.174 0.09 SCL-90R PSDI 2.44 0.55 2.49 0.60 2.29 0.53 2.52 0.56 0.484 0.09 0.032 * 0.27 0.252 0.15 0.001 * 0.35 0.615 0.05 0.001 * 0.41 Novelty 101.88 15.70 99.28 17.08 104.22 15.38 101.97 15.76 0.242 0.16 0.222 0.15 0.965 0.01 0.001 * 0.30 0.081 0.16 0.033 * 0.14 seeking Harm avoidance 121.05 18.82 116.81 20.07 114.81 19.27 122.98 18.02 0.115 0.22 0.007 * 0.33 0.434 0.10 0.232 0.10 0.001 * 0.32 0.001 * 0.44 Reward 104.08 17.36 99.02 14.53 102.35 14.85 102.31 15.68 0.018 * 0.32 0.348 0.11 0.366 0.11 0.013 * 0.23 0.027 * 0.22 0.969 0.00 dependence Persistence 103.64 17.22 106.80 21.26 110.63 19.65 104.18 20.87 0.263 0.16 0.004 * 0.38 0.833 0.03 0.030 * 0.19 0.182 0.12 0.001 * 0.32 Self- 114.07 19.96 113.45 19.45 115.94 19.61 111.05 20.23 0.824 0.03 0.436 0.09 0.238 0.15 0.151 0.13 0.216 0.12 0.001 * 0.25 directedness Cooperativeness 132.88 18.23 130.37 16.32 133.36 15.23 132.57 16.65 0.264 0.14 0.803 0.03 0.881 0.02 0.033 * 0.19 0.158 0.13 0.458 0.05 Self- 68.95 15.31 64.28 14.21 64.98 14.20 66.58 15.82 0.024 * 0.32 0.027 * 0.27 0.213 0.15 0.585 0.05 0.109 0.15 0.104 0.11 transcendence Note: OB: obesity; NW: normal weight; SD: standard deviation; * bold: significant comparison; † bold: effect size into the range mild/moderate (|d| > 0.50) to large/high (|d| > 0.80). Note: OB: obesity; NW: normal weight; NSSI: nonsuicidal self-injury; Vs: versus; * bold: significant comparison; † bold: effect size into the range mild/moderate (|h| > 0.50) to large/high (|h| > 0.80). 3.4. Association between Age of Onset of ED and Age of Maximum BMI Nutrients 2021, 13, 2034 The age of the maximum BMI and age of onset of the ED are shown in Table 4, and 8 of 15 a scatterplot of these data is shown in Figure 2. Most patients in the BMI profile of NW-OB and OB-OB registered the maximum BMI after the onset of the ED. Among OB-NW pa- 3.3. Comparison tients, between the 35.2% registered Groups for Impulsive maximum-ever Behaviors BMI prior to the onset of ED, 27.2% coinciding with NSSI behavior, the onset of ED,suicidal ideation and 37.6% afterand the attempts, andAmong onset of ED. substance use/abuse NW-NW are shown patients, 24.6% in Table 3. The highest proportions of patients who reported NSSI behavior registered maximum-ever BMI prior to the onset of the ED, 22.9% coinciding with were in the OB-NW onset group, of ED, andfollowed by NW-NW, 52.5% after the onsetNW-OB, of ED. and OB-OB groups. The highest prevalence of suicidal behavior (ideation and attempts) was registered among NW-OB and OB-NW groups. The4. lowest Table prevalence Age of onset of alcohol of ED and and drug BMI. age of maximum consumption was registered among the OB-OB group, while OB-NW and NW-NW groups reported the highest prevalence. OB-OB OB-NW NW-NW NW-OB G1 G1 G1 G2 G2 G3 G1; n = 69 G2; n = 125 G3; n = 558 G4; n = 260 vs G2 vs G3 vs G4 vs G3 vs G4 vs G4 3.4. Association between Age of Onset of ED and Age of Maximum BMI Maximum BMI n % n % n % n % p |h| p |h| p |h| p |h| p |h| p |h| Previous onset The age of the maximum BMI and age of onset of the ED are shown in Table 4, and 7 10.1% 44 35.2% 137 24.6% 21 8.1% 0.001 * 0.63 † 0.001 * 0.39 0.564 0.07 0.008 * 0.23 0.001 * 0.70 † 0.001 * 0.51 † ED a scatterplot of these data is shown in Figure 2. Most patients in the BMI profile of NW- Coincides onset OB and 5 7.2% 34 27.2% 128 OB-OB registered 22.9% 12 4.6% the maximum 0.55 † BMI 0.51 †after the 0.11onset of0.10 the ED. Among 0.65 † OB-NW0.55 † ED patients, 35.2% registered maximum-ever BMI prior to the onset of ED, 27.2% coinciding Posterior onset 22 ED with 293 57 82.6% 47 37.6% the onset 52.5% of ED, 7 and 37.6%1.03 87.3% after † the onset 0.68 † of ED.0.13Among 0.30 NW-NW 1.20patients, † 24.6% 0.82 † registered maximum-ever BMI prior to the onset of the ED, 22.9% coinciding with the onset Note: OB: obesity; NW: normal weight; Vs: versus; *bold: significant comparison; †bold: effect size into the range mild/moderate (|h|>0.50) toof ED, and (|h|>0.80). large/high 52.5% after the onset of ED. G1: OB-OB G2: OB-NW Age maximum BMI (yrs-old) Age maximum BMI (yrs-old) Onset ED (yrs-old) Onset ED (yrs-old) G3: NW-NW G4: NW-OB Age maximum BMI (yrs-old) Age maximum BMI (yrs-old) Onset ED (yrs-old) Onset ED (yrs-old) Figure 2. Scatterplot with the age of onset of the ED and the age of the maximum BMI. 3.5. Comparison of the CBT Outcomes between the BMI Profiles Table 5 shows the distribution of the CBT outcomes between the groups (see also Figure 3). The OB-OB BMI profile registered the highest prevalence of dropouts and the lowest of non-remission. The NW-NW BMI profile presented the highest prevalence of non-remission. OB-NW and NW-OB groups achieved the highest prevalence of partial- or full-remission. Nutrients 2021, 13, 2034 9 of 15 Table 3. Comparison between the groups for impulsivity measures. OB-OB OB-NW NW-NW NW-OB G1 G1 G1 G2 G2 G3 G1; n = 74 G2; n = 156 G3; n = 756 G4; n = 314 vs G2 vs G3 vs G4 vs G3 vs G4 vs G4 n % n % n % n % p |h| p |h| p |h| p |h| p |h| p |h| NSSI 18 24.3% 60 38.5% 257 34.0% 90 28.7% 0.034 * 0.31 0.092 0.21 0.454 0.10 0.286 0.09 0.032 * 0.21 0.090 0.12 Suicidal 37 50.0% 85 54.5% 367 48.5% 181 57.6% 0.524 0.09 0.811 0.03 0.233 0.15 0.177 0.12 0.516 0.06 0.007 * 0.18 ideation Suicidal 16 21.6% 39 25.0% 147 19.4% 80 25.5% 0.575 0.08 0.653 0.05 0.489 0.09 0.117 0.13 0.911 0.01 0.028 * 0.14 attempts Alcohol abuse 1 1.4% 16 10.3% 77 10.2% 24 7.6% 0.016 * 0.39 0.013 * 0.39 0.047 * 0.31 0.979 0.00 0.339 0.09 0.195 0.09 Drugs abuse 8 10.8% 28 17.9% 157 20.8% 41 13.1% 0.164 0.20 0.041 * 0.28 0.601 0.07 0.425 0.07 0.158 0.14 0.003 * 0.21 Note: OB: obesity; NW: normal weight; NSSI: nonsuicidal self-injury; vs: versus; * bold: significant comparison. Table 4. Age of onset of ED and age of maximum BMI. OB-OB OB-NW NW-NW NW-OB G1 G1 G1 G2 G2 G3 G1; n = 69 G2; n = 125 G3; n = 558 G4; n = 260 vs G2 vs G3 vs G4 vs G3 vs G4 vs G4 Maximum n % n % n % n % p p p p p p BMI |h| |h| |h| |h| |h| |h| Previous 0.008 onset ED 7 10.1% 44 35.2% 137 24.6% 21 8.1% 0.001 * 0.63 † 0.001 * 0.39 0.564 0.07 * 0.23 0.001 * 0.70 † 0.001 * 0.51 † Coincides onset ED 5 7.2% 34 27.2% 128 22.9% 12 4.6% 0.55 † 0.51 † 0.11 0.10 0.65 † 0.55 † Posterior onset ED 57 82.6% 47 37.6% 293 52.5% 227 87.3% 1.03 † 0.68 † 0.13 0.30 1.20 † 0.82 † Note: OB: obesity; NW: normal weight; vs: versus; * bold: significant comparison; † bold: effect size into the range mild/moderate (|h| > 0.50) to large/high (|h| > 0.80). Table 5. Comparison for the CBT outcomes. OB-OB OB-NW NW-NW NW-OB G1 G1 G1 G2 G2 G3 G1; n = 29 G2; n = 60 G3; n = 282 G4; n = 129 vs G2 vs G3 vs G4 vs G3 vsG4 vs G4 n % n % n % n % p |h| p |h| p |h| p |h| p |h| p |h| Drop out 15 51.7% 21 35.0% 101 35.8% 36 27.9% 0.408 0.34 0.038 * 0.32 0.040 * 0.51 † 0.105 0.02 0.290 0.15 0.081 0.17 Non-remission 1 3.4% 4 6.7% 49 17.4% 21 16.3% 0.15 0.50 † 0.44 0.33 0.31 0.03 Partial-remission 4 13.8% 15 25.0% 69 24.5% 28 21.7% 0.29 0.27 0.21 0.01 0.08 0.07 Full-remission 9 31.0% 20 33.3% 63 22.3% 44 34.1% 0.05 0.20 0.07 0.25 0.02 0.26 Note: OB: obesity; NW: normal weight; vs: versus; * bold: significant comparison; † bold: effect size into the range mild/moderate (|h| > 0.50) to large/high (|h| > 0.80). 3.5. Comparison of the CBT Outcomes between the BMI Profiles Table 5 shows the distribution of the CBT outcomes between the groups (see also Nutrients 2021, 13, 2034 Figure 3). The OB-OB BMI profile registered the highest prevalence of dropouts, and the 10 of 15 lowest of nonremission rates (NW-NW) was related to the highest prevalence of nonre- mission. OB-NW and NW-OB groups achieved the highest prevalence of partial or full remission. 100% 90% 22.3% 31.0% 33.3% 34.1% 80% 70% Outcome 24.5% 60% 13.8% Full-remission 3.4% 25.0% 21.7% 50% Partial-remission 17.4% 40% 6.7% Non-remission 16.3% 30% Dropout 51.7% 20% 35.0% 35.8% 27.9% 10% 0% OB-OB OB-NW NW-NW NW-OB Distribution of Figure 3. Distribution of the the CBT CBT outcome outcome within within the lifetime BMI profiles. Note: OB: OB: obesity; NW: normal weight. 4. Discussion Table 5. Comparison for the CBT outcomes. The present study sought to address an important gap in the literature by examining OB-OB OB-NW NW-NW NW-OB G1 G1 G1 G2 G2 G3 G1; n = 29 whether the weight history of vs G2; n = 60 G3; n = 282 G4; n = 129 patients G2 with vs G3 ED could vs G4 be a vstransdiagnostic G3 vsG4 marker vs G4 of n % n severity % and n treatment % n outcome. % p We |h| analyzed p |h| the p psychopathology |h| p |h| and p dysfunctional |h| p |h| Drop out 15 51.7% 21 personality 35.0% 101 profiles 35.8% 36 of the different 27.9% groups. 0.408 0.34 0.038We0.32also examined 0.040 0.51 0.105whether these 0.02 0.290 BMI 0.15 profiles 0.081 0.17 Non-remission 1 3.4% 4 had 6.7%a different 49 17.4% response 21 16.3%to therapy.0.15 0.50 0.44 0.33 0.31 0.03 Partial-remis- As 69 expected, 4 13.8% 15 25.0% 24.5% the 28 main 21.7% finding 0.29was that0.27 most patients 0.21 with0.01 BED were 0.08in the 0.07 BMI sion profile with current obesity. These results are in line with previous studies suggesting Full-remission 9 31.0% 20 33.3% 63 22.3% 44 34.1% 0.05 0.20 0.07 0.25 0.02 0.26 that BED is strongly associated with excessive body weight gain [11,59], due to the high- Note: OB: obesity; NW: normal weight; Vs: versus; * bold: significant comparison; † bold: effect size into the range calorie overconsumption in absence of compensatory behaviors and the sedentary lifestyle mild/moderate (|h| > 0.50) to large/high (|h| > 0.80). frequently reported by these patients [10,60]. While most patients with OSFED were mainly represented in the BMI profiles with current normal weight (OB-NW and NW-NW), the 4. Discussion patients with BN were more heterogeneous, and they were cited in all the BMI profiles but wereThe present mainly study normal sought to address an important gap in the literature by examining weight. whether the weight history Patients with current obesity of patients with ED (i.e., those could be in OB-OB and a transdiagnostic NW-OB) reported marker of se- the highest verity and treatment outcome. We analyzed the psychopathology levels of motivation for change, specifically greater concern, and subjective intensity and dysfunctional per-of sonality profiles of the different groups. We also examined whether their ED, and a higher desire for treatment. It may suggest that they consider their obesity these BMI profiles had a different related to the ED response to therapy. and, therefore, they are more motivated to seek treatment. This hypothesis would Asbe expected, reinforced theby main ourfinding results was that most showing patients that most with in patients BED thewere OB-OB in the andBMI pro- NW-OB file BMIwith current profiles obesity. recorded theThese results are in maximum-ever BMI lineafter withtheprevious onset of studies the ED. suggesting On the other that BED is strongly associated with excessive body weight gain [11,59], hand, it should be noted that these patients also had a longer duration or chronicity of the due to the high-calorie overconsumption disorder, which has in previously absence of beencompensatory related to behaviors and the sedentary increased motivation lifestyleneed and perceived fre- quently reported for treatment [61]. by these patients [10,60]. While most patients with OSFED were mainly represented The second in themainBMIobjective profiles was withtocurrent examine normal weight the clinical (OB-NW between differences and NW-NW), the groups the patients based onwith BMIBN were more changes heterogeneous, over the lifetime. Our and they were findings cited in all are partially in the BMI profiles agreement with but were mainly previous researchnormal on weightweight. fluctuations. Consistent with previous studies, we found an Patientsbetween association with current lifetimeobesity weight (i.e., those (i.e., changes in OB-OBNW-OB and NW-OB) and OB-NW) reported and a more the highest severe levels of motivation for change, specifically greater concern, general psychopathological state [24]. However, in contrast to other studies [24,25], weand subjective intensity of their foundED, no and a higherbetween association desire for treatment. weight It mayand fluctuations suggest greaterthatED-related they consider their obesity symptomatology. related to the ED Nevertheless, and, therefore, according they are to previous more motivated research to seekcorroborate [11], our results treatment . Thisthat,hypoth- overall, patients esis would with lifetime obesity be reinforced by ourreport resultsgreater showingED that and most general psychopathology, patients in the OB-OBcomparedand NW- to those OB withoutrecorded BMI profiles a history theof obesity (namely BMI maximum-ever NW-NW).after theThis might onset suggest of the ED. On thatthelifetime other obesity, rather than weight fluctuations, is associated with greater psychopathology, regard- less of whether the obesity was before or after the development of the ED. Our findings show that patients who have never had obesity had higher novelty seeking, and were also higher in persistence and self-directedness than those with lifetime obesity. These findings are similar to those reported by Villarejo et al. [11] in which a more dysfunctional Nutrients 2021, 13, 2034 11 of 15 personality profile (characterized by high harm avoidance, and low scores on persistence, self-directedness, and cooperativeness) was described in patients with ED and lifetime obesity. Similarly, high persistence, self-directedness, and self-control have been identified as protective factors for weight gain or obesity development [15]. In addition, this research went a step further and identified the lowest scores on reward dependence and novelty seeking in the group of patients with previous obesity but current normal weight (i.e., OB- NW). Low scores on reward dependence are related to being independent, not influenced by others, nonconformist, socially detached, and insensitive to social pressures. Therefore, although this finding may seem striking, it is in line with a previous study suggesting that people who do not require social support and are more self-confident are more likely to achieve self-directed weight loss [62]. This finding supports the use of therapeutic tools targeted at improving self-reliance, especially in patients with lifetime obesity. On the other hand, our results reveal that patients who achieved a normal weight coming from obesity were those with the lowest scores on novelty seeking. This is consistent with a prior study suggesting that low novelty seeking was associated with weight loss in patients seeking treatment for obesity [63]. Therefore, this finding suggests that using techniques to reduce impulsivity would be useful in the treatment of patients with ED and obesity [64]. Our results also reveal that patients with more extreme weight changes across the lifespan (i.e., OB-NW and NW-OB) endorsed a higher frequency of suicidal ideation and attempts. These results are in line with previous studies reporting more depressive-related symptomatology and severe psychopathology in patients with lifetime weight fluctua- tions [22,24,30]. The OB-NW profile also engaged in more NSSI behaviors. Additionally, this group had the highest frequency of vomiting episodes, which is in line with previous findings suggesting that NSSI is strongly related to purging behaviors and both may serve similar functions in terms of emotion regulation [65]. The lowest prevalence of substance consumption (alcohol and drugs) was registered among OB-OB. As this BMI profile had the lowest frequency of vomiting, our results are also in agreement with previous studies that found a relationship between a higher frequency of purging behaviors and higher substance use [66,67]. Finally, the longitudinal data indicate that patients in both OB-NW and NW-OB groups had the best treatment outcomes, which is inconsistent with the previous literature that had found a relationship between greater weight fluctuations and lower therapeutic adherence and worse treatment outcome [17]. Patients in the OB-OB BMI profile had the highest dropout rates. This novel and noteworthy result calls into question the findings of previous studies reporting that patients with BED had rapid symptoms remission but also high dropout rates, compared to BN [48]. This previous study suggested that patients with BED, most of them with obesity, dropped out more frequently because their desire to lose weight was not addressed by standard CBT. In addition, the current research expands these findings and indicates differences within this type of patient. Although patients with BED were represented in both NW-OB and OB-OB BMI profiles, only those in the latter group presented a higher prevalence of dropout. One possible rationale could be that patients who have developed obesity after the ED onset may consider their weight gain as a consequence of the disorder and dependent on their recovery. Therefore, they may exhibit greater therapeutic adherence. Limitations and Strengths The present study should be considered within the context of several limitations. First, retrospective and self-report data collection (mainly regarding maximum and minimum weight) may limit the validity and reliability of our results. Participants who may have been underweight (BMI < 18.5 kg/m2 ) in the past were not excluded in this study because of the difficulty of interpreting retrospective reports of age-associated BMI changes and the unavailability of height data. Further studies should exclude participants with a lifetime BMI less than 18.5 by controlling for weight and height at each time point. In addition, although we asked for the age of onset of ED and age of maximum and minimum BMI, Nutrients 2021, 13, 2034 12 of 15 our results do not allow us to state that weight changes are a cause or a consequence of the disorder. Second, the low representation of males did not allow for meaningful sex-related comparisons. However, this was representative of the proportion we routinely observe in clinical practice. Third, the motivational scale has not been validated, although it has been used in previous studies [46,49,61]. In this line, further studies should include validated instruments to measure the motivation stage of change. Finally, findings from the longitudinal substudy were based on symptomatological remission after the therapy but not recovery (which requires a long period of abstinence from ED symptomatology). Hence, additional longitudinal studies collecting follow-up data are needed to determine the long-term effect of the associations found. Notwithstanding these limitations, the study also has several strengths that should be noted. To the best of our knowledge, this is the first study examining the potential role of BMI changes across the lifespan in the phenotypic characteristics and severity of patients with ED, as well as their association with therapeutic response. 5. Conclusions In short, our findings provide support for considering the course of BMI as a transdi- agnostic feature that serves as a possible marker of severity and treatment outcome. Our findings corroborate that lifetime obesity is associated with greater general psychopathol- ogy and with some personality traits such as low persistence and self-directedness, and high reward dependence (i.e., low self-confidence). Thus, more functional scores on these personality traits may act as protective factors against weight gain. Finally, a relevant finding from our research reveals that only a subgroup of patients with BED (namely, those in the OB-OB BMI profile) have significantly less treatment adherence and higher dropout rates, which might be because they do not link their obesity to the ED. Thus, the findings derived from this study might improve our ability to identify clinical features related to the symptomatic expression and prognosis of these patients (namely weight changes) and, thereby, aid in tailoring the best treatment targets. Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/nu13062034/s1, Table S1: Comparison between the groups included and not in the substudy 2 of the treatment outcomes. Author Contributions: Conceptualization, Z.A., C.V.-A., I.B., and F.F.-A.; methodology, Z.A. and R.G.; formal analysis, R.G.; investigation, Z.A., C.V.-A., and I.B.; data curation, Z.A. and R.G.; resources, F.F.-A.; writing—original draft preparation, Z.A., C.V.-A., I.B., and R.G.; writing—review and editing, Z.A., S.J.-M., I.S., J.S.-G., J.M.M., J.T., and F.F.-A.; supervision, Z.A. and F.F.-A.; funding acquisition, S.J.-M. and F.F.-A. All authors have read and agreed to the published version of the manuscript. Funding: We thank CERCA Programme/Generalitat de Catalunya for institutional support. This research was partially supported by Instituto de Salud Carlos III (ISCIII; Grant Number: PI17/01167 and PI20/00132), by PERIS (Generalitat de Catalunya, SLT006/17/00246), and co-funded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe. C.V.-A. is supported by a predoctoral Grant of the Ministerio de Educación, Cultura y Deporte (FPU16/01453). I.B. was partially supported by a post-residency grant from the Research Committee of the University Hospital of Bellvitge (HUB; Barcelona, Spain) 2019–2020. CIBERobn and CIBERSAM are initiatives of ISCIII. Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Bellvitge University Hospital (Protocol Code PR149/11, date of approval: 9 June 2011). Informed Consent Statement: Written informed consent was obtained from all subjects involved in the study. Data Availability Statement: Data are not available in any repository. Contact with correspond- ing authors. Nutrients 2021, 13, 2034 13 of 15 Conflicts of Interest: Fernando Fernández-Aranda reports consultation fees from Novo Nordisk and the editor-in-Chief honorarium from Wiley. 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