Impact of virtual adjunctive cognitive remediation therapy on cognitive flexibility and treatment outcomes in comorbid anorexia nervosa and exercise dependence as quantified using novel biomarkers: A stage 1 registered report

Abstract

Objective: Anorexia nervosa (AN) is associated with significant individual mental and physical suffering and public health burden and fewer than half of patients recover fully with current treatments. Comorbid exercise dependence (ExD) is common in AN and associated with significantly worse symptom severity and treatment outcomes. Research points to cognitive inflexibility as a prominent executive function inefficiency and transdiagnostic etiologic and maintaining mechanism linking AN and ExD. This study will evaluate the initial efficacy of adjunctive Cognitive Remediation Therapy (CRT), which has been shown to produce cognitive improvements in adults with AN, in targeting cognitive inflexibility in individuals with comorbid AN and ExD. As an exploratory aim, this study also addresses the current lack of quick and costeffective assessments of cognitive flexibility by establishing the utility of two proposed biomarkers, heart rate variability and salivary oxytocin. Method: We will conduct a single-group, within-subjects trial of an established CRT protocol delivered remotely as an adjunct to inpatient or intensive outpatient treatment as usual (TAU) to adult patients (n = 42) with comorbid AN and ExD. Assessments, including self-report, neuropsychological, and biomarker measurements, will occur at three time points. Results: We expect CRT to increase cognitive flexibility transdiagnostically and consequently, along with TAU, positively impact AN and ExD compulsivity and symptom severity, including weight gain. Discussion: Findings will inform the development of more effective integrative interventions for AN and ExD targeting shared mechanisms and facilitate the routine assessment of cognitive flexibility as a transdiagnostic risk and maintaining factor across psychopathologies in clinical and research settings.Public Significance: Patients with anorexia nervosa often engage in excessive exercise, leading to harmful outcomes, including increased suicidal behavior. This study examines the preliminary efficacy of an intervention that fosters flexible and holistic thinking in patients with problematic eating and exercise to, along with routine treatment, decrease harmful exercise symptoms. This study also examines new biological