Impaired Glymphatic Function in Acute Anorexia Nervosa: An Exploratory DTI-ALPS Study

Anorexia nervosa (AN) is a severe psychiatric disorder associated with widespread systemic and neurobiological alterations, including autonomic dysregulation and brain microstructural changes. The glymphatic system—a perivascular pathway critical for brain waste clearance—depends on these processes for proper function. Here, we investigated glymphatic function using diffusion tensor imaging along the perivascular space (DTI-ALPS) and examined its relationship with autonomic cardiac regulation. We compared DTI-ALPS indices between 22 women with acute AN and 29 healthy female controls (HC), matched for age and education. We examined associations between DTI-ALPS values and heart rate variability (HRV) indices, including mean heart rate (HR), root mean square of successive differences (RMSSD), and standard deviation of normal-to-normal intervals (SDNN). We further tested whether autonomic function mediates the relationship between clinical status (BMI) and glymphatic activity. Individuals with AN exhibited significantly lower DTI-ALPS values compared to HC (1.44 ± 0.10 vs. 1.52 ± 0.13, p = 0.026), indicating altered glymphatic function. In AN, higher DTI-ALPS values correlated with higher HR (r = 0.49, p = 0.021) and lower parasympathetic-related HRV indices (SDNN: r = -0.53, p = 0.019; RMSSD: r = -0.52, p = 0.023). Mediation analysis revealed that HR mediated the relationship between BMI and DTI-ALPS values (β = 0.019, p = 0.028). Our findings suggest that individuals with acute AN exhibit impaired glymphatic function, potentially linked to autonomic dysregulation. These results provide novel insights into the pathophysiology of AN and open new avenues for clinical research.