Claes Norring

Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and, to a large extent, unknown pathophysiology. Structural brain differences, such as global or focal reductions in grey or white matter volumes, as well as enlargement of the sulci and the ventricles, have repeatedly been observed in individuals with AN. However, many of the documented aberrances normalize with weight recovery, even though some studies show enduring changes. To further explore whether AN is associated with neuronal damage, we analysed the levels of neurofilament light chain (NfL), a marker reflecting ongoing neuronal injury, in plasma samples from females with AN, females recovered from AN (AN-REC) and normal-weight age-matched female controls (CTRLS). We detected significantly increased plasma levels of NfL in AN vs CTRLS (median_AN = 15.6 pg/ml, IQR_AN = 12.1–21.3, median_CTRL = 9.3 pg/ml, IQR_CTRL = 6.4–12.9, and p < 0.0001), AN vs AN-REC (median_AN-REC = 11.1 pg/ml, IQR_AN-REC = 8.6–15.5, and p < 0.0001), and AN-REC vs CTRLS (p = 0.004). The plasma levels of NfL are negatively associated with BMI overall samples (β (±se) = −0.62 ± 0.087 and p = 6.9‧10⁻¹²). This indicates that AN is associated with neuronal damage that partially normalizes with weight recovery. Further studies are needed to determine which brain areas are affected, and potential long-term sequelae.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness¹, affecting 0.9–4% of women and 0.3% of men^2,3,4, with twin-based heritability estimates of 50–60%⁵. Mortality rates are higher than those in other psychiatric disorders⁶, and outcomes are unacceptably poor⁷. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)^8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

The interpersonal Structural Analysis of Social Behavior (SASB) model of self-image has repeatedly proven valuable in relation to eating disorder (ED) symptoms and in predicting ED outcome. We studied the association between initial self-image according to the SASB and 12-month outcome, in five diagnostic groups of female ED patients. Based on previous findings, we expected autonomy related variables (self-control/autonomy) would strongly predict outcome in anorexia nervosa (AN) groups, whereas variables related to affiliation (self-attack/love) would moderately predict outcome in bulimia nervosa (BN). Participants were adult female patients, of whom 457 had AN restrictive type, 228 AN binge/purge subtype, 861 BN, 505 other specified ED and 170 binge eating disorder. Data came from the Stepwise clinical database in Sweden. Outcomes were presence/absence of ED diagnosis and self-rated ED symptoms, and we controlled for baseline ED pathology, BMI, age and general psychiatric symptoms. Regression analyses showed that although the pattern differed somewhat between diagnostic groups, high initial self-love and low self-attack/self-blame predicted a more positive 12-month outcome. In some groups (AN/R in particular), these variables remained important even when baseline pathology and age were included in the analyses. Self-image aspects once again display substantial power in predicting outcome in EDs. In AN/R patients, self-love plays an almost as crucial a role as baseline ED pathology in relation to 12-month outcome.

Perfectionism has been found to predict outcomes in the treatment of eating disorders (ED). In the present study, we took advantage of longitudinal data to: a) investigate whether there are different patterns of perfectionism during the first six months after admission in a clinical sample of patients with ED, and b) describe how these patterns are related to long-term outcome. A sample of patients (N=294) from the Coordinated Evaluation and Research at Specialized Units for Eating Disorders database was divided into clusters according to perfectionism patterns measured with the EDI-2 perfectionism scale at baseline, and six months in treatment. Cluster analysis was performed on the extent and perseverance/changeability of self-oriented and socially described perfectionism. Outcome was measured with the EDI-2 and the SCL-63. Frequencies of eating disorder diagnoses were investigated. Five clusters were identified. Low perfectionism was associated with lower levels of ED and psychiatric symptomatology at baseline. There were no significant differences between clusters on outcome variables at 36-month follow-up. Results indicated better psychiatric and psychological health three years after the initial measure. Patterns of relations between the extent and possible changes of perfectionism, measured with the EDI-P at baseline and after six months, did not appear to be associated with long-term outcomes on psychiatric health ratings.

Very little is known about the prevalence of ADHD symptoms in Bulimia Nervosa and Binge Eating Disorder and even less in other eating disorders. This knowledge gap is of clinical importance since stimulant treatment is proven effective in Binge Eating Disorder and discussed as a treatment possibility for Bulimia Nervosa. The objective of this study was to explore the prevalence and types of self-reported ADHD symptoms in an unselected group of eating disorder patients assessed in a specialized eating disorder clinic. In total 1165 adults with an eating disorder were assessed with a battery of standardized instruments, for measuring inter alia ADHD screening, demographic variables, eating disorder symptoms and psychiatric comorbidity. Chi-square tests were used for categorical variables and Kruskal-Wallis tests for continuous variables. Almost one third (31.3 %) of the patients scored above the screening cut off indicating a possible ADHD. The highest prevalence rates (35–37 %) were found in Bulimia Nervosa and Anorexia Nervosa bingeing/purging subtype, while Eating Disorder Not Otherwise Specified type 1–4 and Binge Eating Disorder patients reported slightly below average (26–31 %), and Anorexia Nervosa restricting subtype patients even lower (18 %). Presence of binge eating, purging, loss of control over eating and non-anorectic BMI were related to results indicating a possible ADHD. Psychiatric comorbidity correlated to ADHD symptoms without explaining the differences between eating disorder diagnoses. There is a high frequency of ADHD symptoms in patients with binge eating/purging eating disorders that motivates further studies, particularly concerning the effects of ADHD medication. The finding that the frequency of ADHD symptoms in anorexia nervosa with binge eating/purging is as high as in bulimia nervosa highlights the need also for this group.

Background: Advanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence.Method: Data for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history.Results: Even after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED.Conclusions: In this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline.