# Association of anti SITH 1 antibody titer with mental stress and intracranial aneurysms

## TL;DR

The study found that higher anti-SITH-1 antibody levels are linked to unruptured aneurysms but not their rupture, suggesting chronic stress may not directly cause aneurysm rupture.

## Contribution

This study is the first to investigate the association between anti-SITH-1 antibody titers and intracranial aneurysm rupture in a prospective multi-center cohort.

## Key findings

- Anti-SITH-1 antibody titers were highest in patients with unruptured intracranial aneurysms.
- Chronic mental stress, as indicated by antibody levels, does not appear to directly cause aneurysm rupture.
- Antibody titers correlated with time since aneurysm diagnosis in unruptured cases.

## Abstract

The role of mental stress in intracranial aneurysm rupture remains unclear. Serum anti–SITH-1 antibody titers have been proposed as a potential biomarker of chronic mental stress. This study investigated the association between serum anti–SITH-1 antibody titers and intracranial aneurysm rupture. Between June 2021 and September 2023, patients with ruptured intracranial aneurysms (RIAs), patients with unruptured intracranial aneurysms (UIAs), and healthy controls were prospectively enrolled from five institutions. Baseline characteristics, aneurysm morphology, and lifestyle factors were recorded. Serum anti–SITH-1 antibody titers were quantified using a fluorescent antibody technique. Blood samples were obtained once in each participant: within 1 month after enrollment in the UIA and Control groups, and within 24 h of subarachnoid hemorrhage onset in the RIA group. The primary outcome was the association between serum anti–SITH-1 antibody titer and aneurysm rupture. Eighty-five participants were registered; after exclusions, 24 patients with RIAs were included for analysis, along with 26 patients with UIAs and 23 controls. Baseline characteristics were generally comparable, except for higher statin use in the UIA group (p = 0.012). Larger aneurysm size (p < 0.001), the presence of aneurysmal blebs (p < 0.001), and distinct aneurysm locations (p = 0.001) were more frequent in the RIA group. Anti–SITH-1 antibody titers differed significantly among groups (p = 0.008), being highest in the UIA group, followed by the RIA and Control groups. In the UIA group, antibody titers showed a significant positive correlation with time from diagnosis to study enrollment (p = 0.028). Anti–SITH-1 antibody titers, used as a marker of mental stress, were significantly higher in patients with UIAs than in those with RIAs or in healthy controls. These findings suggest that chronic mental stress is unlikely to play a critical role in aneurysm rupture but may be more prominent in individuals diagnosed with UIAs.

The online version contains supplementary material available at 10.1038/s41598-026-42027-8.