Evaluation of glymphatic system activity by using diffusion tensor image analysis along the perivascular space in patients with differential suicidality

Brain Res Bull. 2026 May 12:111930. doi: 10.1016/j.brainresbull.2026.111930. Online ahead of print.

ABSTRACT

PURPOSE: Glymphatic dysfunction is linked to various neurological conditions, yet its longitudinal role in Major Depressive Disorder (MDD) and suicidal ideation remains unclear. This study used the non-invasive Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) index to evaluate the association between glymphatic function and suicidal ideation over time.

METHODOLOGY: In this prospective longitudinal study, we enrolled 85 patients (31 male and 54 females) comprising 26 healthy controls (HC; mean age: 40.04±10.4 years [95% CI: 35.85-44.22]) and 59 patients with MDD. The patient cohort was categorized by clinical trajectory into three groups: non-suicidal (NS, n=28; 44.75±10.1 [40.82-48.68]), suicidal ideation (SI, n=18; 38.56±11.6 [32.81-44.30]), and improved (IM, n=13; 42.15±13.1 [34.21-50.10]), the latter of which transitioned from an SI to a non-suicidal state between timepoints. Clinical assessments, including the Hamilton Depression Rating Scale (HAM-D), Ruminative Responses Scale (RRS), Hospital Anxiety and Depression Scale-Anxiety (HADS-A), and Beck Scale for Suicide Ideation (BSS), were analyzed alongside diffusion MRI. Research is structured for a longitudinal study that includes (1) healthy controls at two time points, (2) depression without suicidal ideation at two time points, (3) depression with suicidal ideation at two time points, and (4) depression with suicidal ideation converting to depression without suicidal ideation. By calculating the DTI-ALPS index, we aim to obtain estimates of glymphatic activity and its association with clinical assessment. All patients, including healthy controls, were also rescanned at TP2.

KEY RESULTS: At TP1, a significant difference in the DTI-ALPS index (b=1500) was observed between the SI and IM groups, suggesting its potential as a predictor of treatment response. Over two years, the IM group was characterized by a stabilization of glymphatic activity. Notably, differential analysis revealed a significant negative correlation between the DTI-ALPS index and HADS-A scores at follow-up. This inverse relationship indicates that maintained glymphatic function is associated with the reduction of anxiety and depressive symptoms.

CONCLUSIONS: The DTI-ALPS index is closely associated with anxiety-related measures in MDD. These findings highlight glymphatic activity as a potential biological marker for monitoring clinical improvement and the impact of treatment on suicidal ideation.

PMID:42128141 | DOI:10.1016/j.brainresbull.2026.111930