Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a "scar" due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects. METHODS: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters. DISCUSSION: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and "scar" effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.

Potential shortcomings in current studies on the effect of intranasal oxytocin in Anorexia Nervosa and healthy controls - A systematic review and meta-analysis.

RATIONALE: The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN. OBJECTIVE: The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN. METHODS: A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN. RESULTS: Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [- 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = - 0.01 [- 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min. CONCLUSION: The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.

A systematic review of blood-based serotonergic biomarkers in Bulimia Nervosa.

Bulimia Nervosa (BN) is a serious eating disorder, which affects 0.8-2.9% of the young population. The etiology is unknown and biomarkers would support in understanding the pathophysiology of BN, and in identifying BN patients that may benefit from medical treatment. This systematic review aims to answer whether (a) BN deviate from healthy controls in terms of serotonin (5-HT) biomarkers in blood, and whether (b) blood-based 5-HT biomarkers could be used to tailor psychopharmacological treatment in BN. A literature search using PubMed, PsycINFO and Embase was done using the following search terms: "Bulimia Nervosa" AND "serotonin" AND "blood" OR "plasma" OR "serum". 32 studies were included in this systematic review. Several biomarkers and challenge tests were identified and all studies described an association with BN and dysregulation of the 5-HT system compared to healthy controls. Several studies pointed to an association also to borderline symptoms in BN. BN deviate from healthy controls in terms of 5-HT biomarkers in blood supporting an abnormal 5-HT system in BN. 5-HT biomarkers and associated methods could be used to tailor treatment in BN although as yet, most tests described are unpractical for bedside use.