An overview and investigation of relapse predictors in anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: An extensive number of predictors has been examined across the literature to improve knowledge of relapse in anorexia nervosa (AN). These studies provide various recovery and relapse definitions, follow-up durations and relapse rates. The current study summarizes these values and predictors of relapse in AN in a review and meta-analysis. METHOD: The study was executed according to PRISMA guidelines. Different databases were searched and studies in which participants did not receive an official clinical diagnosis were excluded. A quality analysis was performed using the National Institute of Health's Study Quality Assessment Tool. Random-effects meta-analyses were conducted to summarize data. RESULTS: Definitions of relapse and recovery were diverse. During an average follow-up period of 31 months an average relapse rate of 37% was found. Predictive variables from 28 studies were grouped in six categories: age and sex, symptoms and behaviors, AN subtype and duration, weight or weight change, comorbidity, and personality. The studies were characterized by non-significant and contradictory results. Meta-analyses were performed for the predictors age, AN duration, pre-treatment BMI, post-treatment BMI and depression. These yielded significant effects for post-treatment BMI and depression: higher pre-treatment depression (SMD = .40 CI [.21-.59] and lower post-treatment BMI (SMD = -.35 CI [-.63 to -.07]) increased relapse chances in AN. DISCUSSION: Our results emphasized a lack of sufficiently powered studies, consistent results, and robust findings. Solely post-treatment BMI and pre-treatment depression predicted relapse. Future research should use uniform definitions, larger samples and better designs, to improve our understanding of relapse in AN. PUBLIC SIGNIFICANCE: Knowledge about predictors is important to understand high relapse rates. Our study performed a review and meta-analysis of relapse predictors in AN. Related to the heterogeneity in studies examining predictors, an overview of relapse and recovery definitions, follow-up durations and relapse rates for AN was provided. Significant effects were found for post-treatment BMI and pre-treatment depression. More studies with uniform definitions are needed to improve clinical implications.

OBJETIVO: En la literatura se ha examinado un amplio número de predictores para mejorar el conocimiento de la recaída en la anorexia nerviosa (AN). Estos estudios proporcionan diversas definiciones de recuperación y recaída, duraciones del seguimiento y tasas de recaída. El presente estudio resume estos valores y predictores de recaída en AN en una revisión y metaanálisis. MÉTODO: El estudio se realizó siguiendo las directrices PRISMA. Se realizaron búsquedas en diferentes bases de datos y se excluyeron los estudios en los que los participantes no recibieron un diagnóstico clínico oficial. Se realizó un análisis de calidad mediante la herramienta de evaluación de la calidad de los estudios del Instituto Nacional de Salud. Se realizaron metaanálisis de efectos aleatorios para resumir los datos. RESULTADOS: Las definiciones de recaída y recuperación fueron diversas. Durante un período de seguimiento promedio de 31 meses se encontró una tasa media de recaída del 37%. Las variables predictivas de 28 estudios se agruparon en seis categorías: edad y sexo, síntomas y conductas, subtipo y duración de la AN, peso o cambio de peso, comorbilidad y personalidad. Los estudios se caracterizaron por resultados no significativos y contradictorios. Se realizaron metaanálisis para los predictores edad, duración de la AN, IMC pretratamiento, IMC postratamiento y depresión. Éstos arrojaron efectos significativos para el IMC postratamiento y la depresión: una mayor depresión pretratamiento (DME = −,40; IC: [21 a, 59] y un menor IMC postratamiento (DME = −,35; IC: [−,63 a −,07]) aumentaron las probabilidades de recaída en la AN. DISCUSIÓN: Nuestros resultados enfatizaron la falta de estudios con suficiente potencia, resultados consistentes y hallazgos robustos. Sólo el IMC postratamiento y la depresión pretratamiento predijeron la recaída. Las investigaciones futuras deberían utilizar definiciones uniformes, muestras más grandes y mejores diseños, para mejorar nuestra comprensión de la recaída en la AN.

Predictors of recovery in eating disorders: A focus on different definitions.

OBJECTIVE: Only half of the patients with eating disorders (EDs) fully recover. To increase these rates, knowledge about predictors is essential. Previous studies found that purging behaviors, BMI, ED duration, and depression, predicted symptomatic ED recovery. The current study investigated these four predictors for symptomatic improvement and the subjective experience of recovery. METHOD: Participants who completed the baseline and second wave of the Netherlands Eating disorder Registry (NER) (N = 374), were categorized into: (1) Subjective recovery; (2) Clinical improvement; (3) Symptomatic recovery. Using regression analyses, it was investigated if the four baseline factors predicted recovery at wave two. Effects were compared among a binge-purging and restricting group. RESULTS: In total, 136 participants were subjectively recovered, 135 showed clinical improvement, and 70 were symptomatically recovered. Overlap occurred between definitions. Lower depression scores predicted subjective recovery (OR 0.77, p < .001) and clinical improvement (OR 0.80, p < .001), and shorter ED duration predicted all definitions (OR 0.99, p < .001; OR 0.99, p < .001; OR 0.99, p = .013). Similar effects were found in the binge-purging group. DISCUSSION: Our study emphasized that the same predictors, like depression, apply to symptomatic improvement and the personal experience of recovery. Depression appears an important factor during ED treatment. PUBLIC SIGNIFICANCE: Recovery rates for EDs are low. To understand this, knowledge about predictors of ED recovery is essential. This study examined the effects of four established predictors across symptomatic improvement and subjective recovery (a more personal experience of recovery). Lower depression scores predicted both, indicating that depression appears important for multiple definitions of recovery and therefore warrants attention during ED treatment.

Eating disorder psychopathology dimensions based on individual co-occurrence patterns of symptoms over time: a dynamic time warp analysis in a large naturalistic patient cohort.

PURPOSE: Most of the network approaches in eating disorders found the highest degree of centrality for symptoms related to weight and shape concerns. However, longitudinal analyses are scarce and may increase our insight of the complex characteristics and dynamics over time. In the current study, an alternative non-linear method to perform longitudinal network analyses, the dynamic time warp approach, was used to examine whether robust dimensions of eating disorder psychopathology symptoms could be found based on the individual dynamic interplay of eating disorder symptoms co-occurrence patterns in time. METHODS: The study sample included a naturalistic cohort of patients (N = 255) with all eating disorder subtypes who were assessed with the eating disorder examination questionnaire (EDE-Q) at a minimum of four times during treatment. Dynamic time warp analyses yielded distance matrices within each individual patient, which were subsequently aggregated into symptom networks and dimensions at the group level. RESULTS: Aggregation of the individual distance matrices at the group level yielded four robust symptom dimensions: 1. restraint/rules, 2. secret eating/fasting, 3. worries/preoccupation, and 4. weight and shape concern. The items 'fear of weight gain' and 'guilt' were bridge symptoms between the dimensions 1, 3 and 4. CONCLUSION: Dynamic time warp could capture the within-person dynamics of eating disorder symptoms. Sumscores of the four dimensions could be used to follow patients over time. This approach could be applied in the future to visualize eating disorder symptom dynamics and signal the central symptoms within an individual and groups of patients. LEVEL OF EVIDENCE: Level III: evidence obtained from well-designed cohort or case-control analytic studies. .

Self-assessment of eating disorder recovery: Absence of eating disorder psychopathology is not essential.

OBJECTIVE: The definition of recovery in eating disorders (EDs) according to researchers is not necessarily similar to the patient definition. This study aimed to explore the concept of recovery as assessed by those affected by an ED themselves. METHOD: Participants from the Netherlands Eating disorder Registry (NER) who reported an (former) ED diagnosis (n = 814) assessed their own recovery level: current ED, partial or full recovery. Furthermore, research-based criteria (Bardone-Cone et al., Behaviour Research and Therapy, 2010, 48, 194-202) were applied to define recovery. Within the self-assessed full recovery group (n = 179), participants who also fulfilled the research-based criteria were compared to those who were only recovered based on self-assessment in the following domains: ED psychopathology, psychiatric comorbidity, quality of life, and social and societal participation. RESULTS: Ninety-six of the participants (54%) who considered themselves recovered did not fulfill the research-based definition. The two recovery groups did not significantly differ in psychiatric comorbidity, quality of life, and social and societal participation. DISCUSSION: Absence of ED characteristics was not essential for individuals to consider themselves recovered. Although the self-assessed recovery status may be subjective, it does advocate the use of additional health indicators besides ED psychopathology when defining recovery.

Prevalence of dieting and fear of weight gain across ages: a community sample from adolescents to the elderly.

OBJECTIVES: The current study aimed to define the prevalence of dieting and fear of weight gain among men and women across the entire lifespan and identify factors associated with them. METHODS: Data were available for 31,636 participants (60.2% women; age 13-98 years) from the Netherlands Twin Register. Dieting and fear of weight gain were described by age and sex. Associations with BMI, exercise behavior, urbanization and educational attainment were examined by regression analyses in 19,294 participants. RESULTS: Dieting was most frequently reported by 35- to 65-year-old women (56.6-63%), and 45- to 65-year-old men (31.7-31.9%). Fear of weight gain was most prevalent in women between 16 and 25 (73.2-74.3%), and in 25- to 55-year-old men (43.2-46.1%). In addition to sex and BMI, dieting and fear of weight gain were associated with each other. Furthermore, fear was associated with the age × sex interaction and educational attainment. CONCLUSIONS: Dieting and fear of weight gain is common during the entire lifespan for women, but is also endorsed by a substantial number of men. Given the low rate of overweight in young women, the high levels of fear of weight gain are striking.

Classifying eating disorders based on "healthy" and "unhealthy" perfectionism and impulsivity.

OBJECTIVE: Perfectionism and impulsivity are associated with eating disorders (EDs). The current study examines whether clinically relevant subgroups of women with EDs can be identified based on "healthy" and "unhealthy" perfectionism and impulsivity. METHOD: Latent profile analyses (LPA) were performed on data of 844 patients (DSM-IV diagnosis: 381 anorexia nervosa, 146 bulimia nervosa, 56 binge-eating disorder, 261 ED not otherwise specified). "Healthy" and "unhealthy" forms of perfectionism and impulsivity were assessed by the Frost Multidimensional Perfectionism Scale and the Dickman Impulsivity Inventory, respectively. The Eating Disorder Examination Questionnaire was completed to assess ED psychopathology. Furthermore, in 229 patients additional ED symptoms, depression, self-esteem, obsessive-compulsive symptoms, and personality features were assessed. RESULTS: The LPA revealed four profiles; 1. "Healthy Impulsivity" (HI; n = 191), 2. "Unhealthy Impulsivity" (UI; n = 238), 3. "Healthy and Unhealthy Perfectionism" (HP + UP; n = 153), 4. "Healthy Perfectionism" (HP; n = 262). Patients belonging to the "HP + UP" and the "UI" classes reported higher levels of ED psychopathology. More severe comorbid symptoms (depressive, obsessive-compulsive and self-esteem) were found in the patients belonging to the "HP + UP" class. Patients from the "HP + UP" and "HP" classes had higher scores for the personality features Harm Avoidance, Persistence and Cooperativeness. DISCUSSION: Women with EDs could be meaningfully grouped according to perfectionism and impulsivity. These findings can be used to improve treatment matching and intervention strategies. The use of dimensional features, like perfectionism and impulsivity, in ED research, may enable the identification of fundamental underlying mechanisms and provide more insight into potential mechanisms that may drive or maintain disordered eating. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:673-680).

Predictors of psychological outcome in patients with eating disorders: A routine outcome monitoring study.

BACKGROUND: Identifying predictors of psychological outcome for patients with eating disorders may improve the effectiveness of treatment. Patients with different pre-treatment characteristics and symptoms may benefit from different therapies. This study aimed to identify potential predictors of treatment outcome in a large naturalistic cohort of patients with an eating disorder. METHOD: The study sample included patients (N = 1153) with all types of eating disorders who were receiving residential, day, or outpatient treatment. Remission was defined by means of four different indicators based on the Eating Disorder Examination-Questionnaire global score: 1. achieving reliable change; 2. showing a 50% reduction in baseline symptom severity; 3. reaching the clinical significance cut-off point; and 4. a combination of indicators 2 and 3. Potential predictor variables were investigated in univariate and multivariate Cox regression models. RESULTS: Different predictors were found for the four outcome criteria. Patients with high levels of interpersonal distrust at baseline were less likely to have achieved reliable change in eating disorder psychopathology. Higher self-esteem and less body dissatisfaction at baseline was independently associated with a symptom reduction of more than 50% and/or reaching the clinical significance cut-off point. Contrary to our expectations, no differences in outcome were found between the eating disorder subtypes. DISCUSSION: Clinically, it is important to reduce the risk of poor outcome and to achieve a rapid response in treatment using an intervention designed for this purpose, such as shared decision making or an intervention directed at self-esteem or body image, which may act as a catalyst for change. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:863-873).

A common mineralocorticoid receptor polymorphism (I180V) interacts with life events in relation to perfectionism in eating disorders: a pilot study.

The stress response is regulated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). When the balance between GR and MR signalling is disturbed, one's capacity to cope with a stressful event is diminished. In this pilot study, we tested the hypothesis that an interaction between common variants in the MR (rs5522) or GR gene (rs41423247) and stressful life events influences perfectionism levels in a group of patients with an eating disorder (ED; n = 113). Patients carrying the minor G allele of rs5522 had a higher perfectionism score if more stressful life events were experienced [ß = 0.95, t(109) = 3.75, p < 0.01]. This effect was not found for patients carrying the AA genotype. These results suggest that rs5522 G allele carriers might be vulnerable to stressful life events. When patients with an ED are carriers and experience multiple life events, this might fuel their insecurity, which in turn may engender higher levels of perfectionism. Further studies are necessary to replicate and expand our findings.

Association study of the estrogen receptor I gene (ESR1) in anorexia nervosa and eating disorders: no replication found.

OBJECTIVE: The female preponderance and onset around puberty in the majority of eating disorders (EDs) suggest that sex hormones, like estrogens, may be involved in the onset of these disorders. An eight-SNP haplotype at the estrogen receptor I (ESR1) gene was found to be associated with anorexia nervosa (AN) (Versini et al., Neuropsychopharmacology, 35, 1818-1825, 2010) and three SNPs from this haplotype (rs726281, rs2295193, and rs3798577) were associated with AN and/or EDs. Our objective was to replicate these findings in an independent cohort of 520 patients with an eating disorder, of whom 244 had AN (142 restricting type) from the GenED study and 2,810 random women from the Netherlands Twin Registry. METHOD: The frequencies of the eight-SNP haplotype and three ESR1 SNPs were compared between patients with an eating disorder, with AN (restricting type), with bulimia nervosa (BN), and the control women. RESULTS: Neither the haplotype nor the three ESR1 SNPs were associated with EDs, BN, AN, or restricting type AN. DISCUSSION: Despite sufficient statistical power, the associations reported by Versini et al. (Neuropsychopharmacology, 35, 1818-1825, 2010) were not replicated.

Genetic variation at the TPH2 gene influences impulsivity in addition to eating disorders.

Genes are involved in eating disorders (EDs) and self-induced vomiting (SV), a key symptom of different types of EDs. Perfectionism and impulsivity are potential risk factors for EDs. TPH2 (tryptophan hydroxylase 2) SNP rs1473473 was previously associated with anorexia nervosa and EDs characterized by SV. Could perfectionism or impulsivity be underlying the association between rs1473473 and EDs? Genetic association between TPH2 SNP rs1473473 and perfectionism or impulsivity was first evaluated in a random control group (N = 512). The associations obtained in this control group were subsequently tested in a group of patients with an ED (N = 267). The minor allele of rs1473473 (OR = 1.49) was more frequent in impulsive controls, but also in impulsive patients with an ED (OR = 1.83). The largest effect was found in the patients with an ED characterized by SV (OR = 2.51, p = 0.02). Genetic variation at the TPH2 gene appeared to affect impulsivity which, in turn, might predispose to the SV phenotype.

The Val66Met polymorphism of the BDNF gene in anorexia nervosa: new data and a meta-analysis.

OBJECTIVES: The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). METHODS: We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and family-based studies testing this SNP in AN, and combined the results in a meta-analysis. RESULTS: The results of the case-control study were non-significant. For the meta-analysis, nine studies were identified (ncases = 2,767; ncontrols = 3,322, ntrios = 53) and included. Primarily, the analyses indicated an association with OR of 1.11 (P = 0.024) in the allelic contrast, and OR of 1.14 (P = 0.025) for the dominant effect of the Met allele. However, additional analyses revealed that the first published study (from those included in the meta-analysis) overly influenced the pooled effect size (possibly due to a phenomenon known as a winner's curse). When this case-control study was replaced by a trio study (ntrios = 293) performed on a largely overlapping sample, the effect size became smaller and non-significant, both for the allelic contrast (OR = 1.07, P = 0.156) and the dominant effect (OR = 1.07, P = 0.319). The quality of included studies was good and there was no significant heterogeneity across the effect sizes. CONCLUSIONS: Our analyses indicate that the BDNF Val66Met variant is not associated with AN at detectable levels.

Norms and discriminative validity of the Eating Disorder Examination Questionnaire (EDE-Q).

The first aim of this study was to provide norms for the Eating Disorder Examination Questionnaire (EDE-Q) in a diverse and large clinical sample of individuals with an eating disorder (ED), and a general population sample without an ED. Norms for individuals with obesity without an ED were also provided, as a more relevant comparison group for individuals with binge eating disorder. The second aim was to investigate the discriminative validity of the EDE-Q. A sample of females with an ED (N=935), women from the general population without an ED (N=235), and obese females without an ED (N=321) completed the EDE-Q. Explorative factor analyses did not support the theorized four subscales of the EDE-Q. Norms for EDE-Q global scores were provided for each of the three samples. Within the ED sample, norms were provided separately for patients with different ED diagnoses. Receiver operating characteristic analyses showed the EDE-Q global score to be highly accurate in discriminating individuals with an ED from those without, and moderately accurate in discriminating individuals with binge eating disorder from those with obesity. The presented norms contribute to a more accurate interpretation of EDE-Q scores, providing an index of the severity level of ED psychopathology. Furthermore, these norms can be used to assess clinical significant change during treatment. In addition, this study demonstrates that the EDE-Q, when using its global score, is a valid instrument to assess levels of ED psychopathology.

Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data.

OBJECTIVES: This study aimed to test the association between the Val158Met polymorphism (rs4680) of the catechol-O-methyl transferase gene and anorexia nervosa (AN). METHODS: First, an association study on two cohorts (306 cases and 1009 controls from Utrecht, and 174 cases and 466 controls from Leiden/NTR) was performed. Subsequently, the results were integrated into a meta-analysis, together with all the case-control and family-based studies, which were testing the same hypothesis and were available in the literature. Altogether, eight studies (11 datasets) were included in this meta-analysis, with a total of 2021 cases, 2848 controls, and 89 informative (heterozygous) trios. RESULTS: The present association studies found no association between AN and rs4680 when testing the allelic contrast [Utrecht odds ratio (OR)=1.14, P=0.14; Leiden OR=1.02, P=0.85]. There was an indication of an association under the dominant model of genetic effect in the Utrecht cohort (for the Met allele, OR=1.42, P=0.03). Nevertheless, the meta-analyses of both the allelic contrast and the dominant effect were nonsignificant (the allelic pooled OR=1.03, P=0.42 and the dominant pooled OR=1.1, P=0.18). The meta-analyses were performed under the fixed-effect model and there was no significant heterogeneity among the effect sizes. CONCLUSION: Meta-analytically combined evidence from the present genotypings and the literature search shows that the effect sizes are homogeneous across studies and that rs4680 is not associated with AN.

Influence of candidate genes on attention problems in children: a longitudinal study.

Attention problems form one of the core characteristics of Attention-Deficit Hyperactive Disorder (ADHD), a multifactorial neurodevelopmental disorder. From twin research it is clear that genes play a considerable role in the etiology and in the stability of ADHD in childhood. Association studies have focused on genes involved in the dopaminergic and serotoninergic systems, but with inconclusive results. This study investigated the effect of 26 Single Nucleotide Polymorphisms (SNPs) in genes encoding for serotonin receptors 2A (HTR2A), Catechol-O-Methyltransferase (COMT), Tryptophane Hydroxylase type 2 (TPH2), and Brain Derived Neurotrophic Factor (BDNF). Attention problems (AP) were assessed by parental report at ages 3, 7, 10, and 12 years in more than 16,000 twin pairs. There were 1148 genotyped children with AP data. We developed a longitudinal framework to test the genetic association effect. Based on all phenotypic data, a longitudinal model was formulated with one latent factor loading on all AP measures over time. The broad heritability for the AP latent factor was 82%, and the latent factor explained around 55% of the total phenotypic variance. The association of SNPs with AP was then modeled at the level of this factor. None of the SNPs showed a significant association with AP. The lowest p-value was found for the rs6265 SNP in the BDNF gene (p = 0.035). Overall, our results suggest no evidence for a role of these genes in childhood AP.

The genetics of anorexia nervosa.

Anorexia nervosa is a perplexing illness marked by low body weight and persistent fear of weight gain. Anorexia nervosa has the highest mortality rate of any psychiatric disease. Historically, anorexia nervosa was viewed as a disorder primarily influenced by sociocultural factors; however, over the past decade, this perception has been challenged. Family studies have consistently demonstrated that anorexia nervosa runs in families. Twin studies have underscored the contribution of additive genetic factors to the observed familial aggregation. With these bodies of literature as a starting point, we evaluate critically the current state of research on molecular genetic studies of anorexia nervosa and provide guidance for future research.

Associations among postpartum depression, eating disorders, and perfectionism in a population-based sample of adult women.

OBJECTIVE: The current study investigated associations among eating disorders, depressive symptoms during pregnancy and postpartum, and perfectionism in a population-based sample of women. METHOD: Females who reported > or = 1 pregnancy (N = 1,119) completed questionnaires assessing perfectionism, eating disorder symptomatology, and depression during pregnancy and postpartum. Information regarding participants' history of major depressive disorder (MDD) was also available from structured psychiatric interviews completed during a previous wave of data collection. RESULTS: Depressive symptoms during pregnancy and postpartum were high among women with a history of eating disorders. Both binge eating disorder (BED) and bulimia nervosa (BN) were positively associated with symptoms of postpartum depression (PPD), even when lifetime MDD was controlled. However, logistic regression indicated that women with a history of BN and BED are at particular risk of developing PPD symptomatology. Linear regression analyses conducted with the subset of the sample who endorsed a PPD screening item suggested that the severity of PPD symptomatology may be attributable to Concern Over Mistakes, a specific aspect of perfectionism. CONCLUSION: These results highlight the importance of assessing specific features of perfectionism. In addition, they suggest that women with BN, BED, or high Concern over Mistakes may be at particular risk of developing PPD symptoms, and could benefit from prenatal screening.

Eating disorders: from twin studies to candidate genes and beyond.

Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.