Anorexia Nervosa

Anorexia nervosa (AN) is a complex metabolic and psychological disorder that is influenced by both heritable genetic components and environmental factors. Exposure to various environmental influences can lead to epigenetically induced changes in gene expression. Epigenetic research in AN is still in its infancy, and studies to date are limited in determining clear, valid links to disease onset and progression are limited. Therefore, the aim of this systematic review was to compile and critically evaluate the available results of epigenetic studies specifically in AN and to provide recommendations for future studies. In accordance with the PRISMA guidelines, a systematic literature search was performed in three different databases (PubMed, Embase, and Web of Science) through May 2023. Twenty-three original papers or conference abstracts on epigenetic studies in AN were collected. Epigenome-wide association studies (EWASs), which analyze DNA methylation across the genome in patients with AN and identify potential disease-relevant changes in promoter/regulatory regions of genes, are the most promising for future research. To date, five EWASs on AN have been published, suggesting a potential reversibility of malnutrition-induced epigenetic changes once patients recover. Hence, determining differential DNA methylation levels could serve as a biomarker for disease status or early diagnosis and might be involved in disease progression or chronification. For future research, EWASs with a larger sample size, longitudinal study design and uniform methods should be performed to contribute to the understanding of the pathophysiology of AN, the development of individual interventions and a better prognosis for affected patients.

ImportanceAnorexia nervosa (AN) is commonly associated with cardiovascular complications.ObjectiveTo investigate the trajectories of the risk of cardiovascular conditions in a nationwide cohort of patients with AN in Taiwan.Design, setting, and participantsFrom a population-based health insurance database from January 1, 2011, to December 31, 2021, this longitudinal cohort study identified patients with AN and controls through propensity score matching at a 1:10 ratio according to sex, age, urbanization level of residence, socioeconomic status, and year of diagnosis. Data were analyzed from June 27, 2023, to February 23, 2024.ExposureFirst-time diagnosis of AN by psychiatrists during the study period.Main outcomes and measuresIncidence and risk of composite cardiovascular conditions. Kaplan-Meier curves were used to estimate the cumulative incidence of major adverse cardiovascular events (MACE) and any cardiovascular condition. With adjustment for psychiatric comorbidities, conditional Cox proportional hazards regression analyses were performed to estimate the risk of cardiovascular events, which were presented as hazard ratios (HRs) and 95% CIs, relative to the comparison group. Risks of individual cardiovascular conditions were calculated during 3 follow-up periods after AN diagnosis.ResultsThe study population included 2081 patients with AN and 20 810 matched controls, for a total of 22 891 participants (mean [SD] age, 24.9 [9.9] years; 91.3% female). In total, 99 patients with AN (4.8%) had MACE vs 175 (0.8%) in controls, and 124 patients with AN (6.0%) had any cardiovascular condition vs 483 controls (2.3%). At the 5-year follow-up, the cumulative incidence rate of MACE was 4.82% (95% CI, 3.85%-6.02%) and of any cardiovascular condition was 6.19% (95% CI, 5.19%-7.53%). Compared with the control group, the AN group had significantly higher risks of MACE (adjusted HR [AHR], 3.78; 95% CI, 2.83-5.05) and any cardiovascular condition (AHR, 1.93; 95% CI, 1.54-2.41). The significantly increased risks of congestive heart failure, conduction disorder, and structural heart disease occurred in the initial follow-up period and disappeared after 60 months of follow-up. Notably, patients with AN did not have an increased risk of ischemic heart disease until after 60 months of follow-up (AHR, 3.01; 95% CI, 1.48-6.13).Conclusions and relevanceIn this national matched cohort study, increased risk of cardiovascular conditions was found in different periods after AN diagnosis. Clinicians should monitor comorbid cardiovascular conditions among patients with AN at initial presentation, during treatment, and at follow-up.

IntroductionSleep is crucial for physical and psychological health, and disturbances are closely linked to psychiatric disorders, making their management essential for improving treatment outcomes and preventing relapse. Although sleep disturbances are implicated in psychopathology of eating disorders, its role in anorexia nervosa (AN) remains unclear. This review aimed to characterise sleep in AN.MethodsA systematic search was conducted in four scientific databases, including papers from inception to 25 May 2024. A machine learning algorithm (ASReview) was utilised to screen titles and abstracts for eligibility. Sleep quantity, architecture, and quality were investigated. Meta-analyses were conducted to investigate the difference between patients with AN and healthy controls (HC) in total sleep time (TST), wake after sleep onset (WASO), sleep onset latency (SOL), sleep efficiency, Sleep Stage 1, 2, slow wave sleep, rapid eye movement (REM) sleep and REM latency. Certainty of evidence was assessed using the GRADE approach.ResultsOut of 67 potentially eligible papers, 31 were included in this review, with 15 in the meta-analyses. Statistically significant average mean differences were found for TST (-32.1 min [95% CI: -50.9, -13.4]), WASO (19.0 min [95% CI: -2.4, 40.3]), and sleep efficiency (-4.4% [95% CI: -7.9, -0.9]). Additionally, Sleep stage 1 was significantly increased (2.4% [95%-CI: 0.05, 4.7]), while REM sleep was reduced (-2.1% [95%-CI: -4.2, -0.02]). Subgroup analysis showed that TST and WASO did not improve significantly after weight restoration.ConclusionSleep in patients with AN is impaired, with lower TST and sleep efficiency, higher WASO, more time in stage 1 sleep, and less in REM. Weight restoration alone may not improve sleep. While more research is needed, substantial accompanying sleep disturbances in AN justifies addressing these in current treatment practice, also because of the chronic character of AN and importance of sleep for long term (mental) health.

ObjectiveAnorexia nervosa (AN) has one of the highest mortality rates among psychiatric disorders. This systematic review and meta-analysis examined the all-cause mortality of AN patients compared to the general population using the standardized mortality ratio (SMR).MethodMEDLINE, PsycINFO, EMBASE, WOS, Dissertations and Theses A&I, and Google Scholar were searched from inception to May 2025 for longitudinal studies reporting all-cause SMR for AN patients. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis was conducted and presented as a forest plot. Subgroup and meta-regression analyses were done. SMRs for male- and female-specific samples were compared.ResultsThirty studies involving 33,176 patients were identified. The pooled SMR from 22 studies was 5.06 (95% CI [3.47-7.38]). Suicide and cardiac deaths accounted for 21% and 19% of deaths, respectively. Studies with lower mean BMI were associated with higher SMRs before correction for multiple testing (p = 0.018, adjusted p = 0.252). The pooled SMR of male-specific samples was 3.47, 95% CI (1.60-7.52), similar to female-specific samples (3.86, 95% CI [1.82-8.20]).DiscussionsOur findings confirm that AN remains a severe psychiatric disorder, underscoring the clinical importance of suicide prevention and monitoring cardiac complications. A low BMI is a crucial clinical indicator for high-risk groups and allocating resources. Limitations include excluding studies with zero deaths, substantial heterogeneity among included studies, the underrepresentation of male and non-Western populations, and most studies originating from specialist clinics.