Sleep Architecture, Inflammatory and Hormonal Biomarkers, Psychopathology, and Quality of Life in Adolescent Girls With Anorexia Nervosa: A Prospective Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 25
研究概览
简要总结
The purpose of this observational study is to systematically evaluate how a 12-month multimodal psychiatric treatment program affects sleep quality, inflammatory and hormonal biomarkers, eating disorder psychopathology, and health-related quality of life in adolescent girls (aged 10-18 years) diagnosed with anorexia nervosa.
The main questions it aims to answer are:
- Do adolescent girls with anorexia nervosa have measurable changes in sleep patterns (total sleep time, sleep efficiency, REM sleep, deep sleep) compared to age- and sex-matched published values, and do these improve after 12 months of psychiatric treatment?
- Are specific body markers (like NLR, CRP, vitamin D, and lipid profile) linked to how severe sleep problems, eating disorder symptoms, and treatment results are in this group?
- To assess these outcomes, researchers will compare participants' baseline measurements to their own 12-month follow-up measurements to determine whether multimodal psychiatric treatment produces clinically meaningful improvements in sleep architecture, biomarker profiles, psychopathology, psychological flexibility, and quality of life.
Participants will:
- Take-home sleep recordings with a wireless device (NOX A1) in their usual environment at the start and after 12 months of treatment.
- Complete validated self-report questionnaires assessing sleep quality (PSQI), daytime sleepiness (ESS-CHAD for children and adolescents), eating disorder symptoms (EDE-Q), depression, anxiety, and stress (DASS-21), psychological flexibility (AFQ-Y8), and health-related quality of life (KIDSCREEN-52) at baseline and 12-month follow-up.
- Give blood samples at the start and after 12 months for testing of inflammation markers, hormone levels, lipids, and anthropometric measurements.
- Take part in a Day Hospital Program at the Department of Psychiatry, University Hospital of Split (KBC Split), Croatia, which includes Acceptance and Commitment Therapy, Cognitive Behavioral Therapy, individual counselling, family work, and medication if needed.
详细描述
Anorexia nervosa (AN) is a severe psychiatric disorder defined by restrictive food intake, significant weight loss, distorted body image, and an intense fear of weight gain, resulting in a three times higher mortality rate among individuals with AN than in the general population. The peak incidence occurs at 14 years of age, with a prevalence of approximately 1.7% among adolescent girls. While early intervention during adolescence is associated with improved outcomes, chronic illness persisting into adulthood often results in recovery rates of only 20-30%.
Sleep disturbances are a clinically significant yet systematically underinvestigated aspect of AN. Almost 50% of individuals with AN report sleep difficulties, irrespective of disorder subtype. A 2024 meta-analysis demonstrated that patients with AN exhibit changes in sleep architecture resulting in significantly shorter total sleep time (TST), reduced sleep efficiency (SE), prolonged wake after sleep onset (WASO), increased N1 non-REM sleep, and reduced REM sleep compared to healthy controls, and especially reduced slow-wave sleep (SWS). Reduced quality of sleep is associated with poorer treatment compliance, increased therapy discontinuation, and a reduced probability of recovery. Notably, weight restoration alone does not regularly normalize sleep architecture, indicating that sleep disturbances require targeted clinical attention independent of nutritional rehabilitation.
The mechanisms underlying sleep disturbances in AN remain unclear. Malnutrition induces hormonal alterations, including elevated ghrelin and orexin-A, decreased leptin, and increased cortisol, that, combined, promote wakefulness and disrupt circadian rhythms. AN is uniquely associated with a morning chronotype, in contrast to most other psychiatric conditions, which are linked to eveningness; this distinction has recently been confirmed by Mendelian randomization studies. Comorbid depression and anxiety, which are highly prevalent in AN, further induce sleep difficulties via overlapping neurobiological pathways.
The majority of current literature has focused on adult populations. Adolescent-specific data remain limited and methodologically inconsistent, with most studies relying on questionnaire-based measures or laboratory polysomnography, both of which are subject to first-night effects.
To date, no published study has combined objective home-based sleep measurement with comprehensive longitudinal biomarker assessment specifically in early-to-mid-adolescent girls with AN. The increasing frequency of pre-menarchal presentations in clinical practice further indicates the necessity for pediatric-focused evidence. In addition to sleep, peripheral biomarkers in AN remain incompletely characterized in adolescents. Data from adult cohorts indicate elevated inflammatory cytokine levels, low-grade systemic inflammation, altered thyroid and prolactin function, dyslipidemia, and reduced 25-hydroxyvitamin D. The neutrophil-to-lymphocyte ratio (NLR), a readily available marker of physiological stress and systemic inflammation, is dysregulated in adult AN. However, the applicability to the adolescent population and their evolution over time with treatment remain insufficiently investigated.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female sex assigned at birth
- •Age between 10 and 18 years (inclusive) at the time of study enrollment
- •First-time diagnosis of anorexia nervosa according to ICD-10 criteria at the time of enrollment, including:
- •Anorexia nervosa (F50.0)
- •Atypical anorexia nervosa (F50.1)
- •Eating disorder, unspecified (F50.9) with predominant restrictive or anorexic presentation
- •Currently under the care of a child and adolescent psychiatrist at the Department of Psychiatry, University Hospital of Split (KBC Split), Croatia
- •Enrolled in or eligible for the Day Hospital Program for Children and Adolescents at the Department of Psychiatry, KBC Split
- •Ability to read and understand Croatian language sufficiently to complete self-report questionnaires
- •Parent or legal guardian willing and able to provide written informed consent prior to any study procedure
- •Participant willing and able to provide written assent prior to any study procedure
- •Participant and parent/guardian willing to undergo all study procedures at both time points, including:
- •Home polysomnography (NOX A1) at baseline and 12-month follow-up
- •Completion of all self-report questionnaires at baseline and 12-month follow-up
- •Fasting blood sampling at baseline and 12-month follow-up
排除标准
- •Age younger than 10 years or older than 18 years at the time of enrollment
- •Male sex assigned at birth
- •Previous diagnosis of anorexia nervosa prior to current enrollment (i.e., recurrent or relapsing AN - this study enrolls first-diagnosis cases only)
- •Anorexia nervosa currently in clinical remission at the time of enrollment
- •Comorbid psychiatric diagnosis of any of the following:
- •Intellectual disability (any severity, ICD-10: F70-F79)
- •Autism spectrum disorder (ICD-10: F84)
- •Schizophrenia spectrum or other psychotic disorder (ICD-10: F20-F29)
- •Bipolar affective disorder, any type (ICD-10: F31)
- •Substance use disorder, any substance (ICD-10: F10-F19)
- •Severe or chronic somatic illness documented in medical history, including but not limited to:
- •Central nervous system disorders (epilepsy, acquired brain injury, neurodegenerative disease, ICD-10: G00-G99)
- •Chronic inflammatory or autoimmune disease (e.g., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis)
- •Primary endocrine disorder independent of AN (e.g., primary hypothyroidism, type 1 or type 2 diabetes mellitus, congenital adrenal hyperplasia)
- •Active or history of malignancy
- •Chronic renal or hepatic disease
- •Use of any medication known to significantly alter sleep architecture or inflammatory biomarker levels that was initiated prior to study enrollment and is unrelated to the study treatment program, including:
- •Benzodiazepines or z-drugs (zopiclone, zolpidem)
- •Antipsychotic medications
- •Systemic corticosteroids
- •Immunosuppressive agents
- •Melatonin or melatonin receptor agonists Medications initiated as part of the Day Hospital treatment program after enrollment will be documented and included as covariates in statistical analyses and do not constitute an exclusion criterion.
- •Presence of an active somatic condition at the time of enrollment requiring acute inpatient medical treatment (e.g., severe electrolyte imbalance requiring intravenous correction, acute cardiac arrhythmia) that would preclude safe participation in the Day Hospital Program
- •Physical or cognitive inability to cooperate with home polysomnography device placement or self-report questionnaire completion, as judged by the treating child and adolescent psychiatrist
- •Simultaneous participation in another interventional clinical trial that could influence sleep parameters, nutritional status, inflammatory markers, or psychiatric outcomes.
- •Absence of written informed consent from parent or legal guardian, or absence of written assent from the participant