Atrophy of hypothalamic subregions increases migraine risk: cross-sectional study and mendelian randomization analysis.

BACKGROUND

The hypothalamus is a versatile structure comprising several nuclei that play key roles in regulating various biological processes associated with migraine, including hormone secretion, metabolism, circadian rhythm, and autonomic nervous system functions. However, the involvement of hypothalamic subregions in migraine remains unclear.

METHODS

Based on T1-weighted MRI data from 76 migraine patients (23 episodic migraine [EM], 53 chronic migraine [CM]) and 35 healthy controls (HCs), we examined group differences in the volume of five hypothalamic subregions. To clarify causal relationships between migraine and hypothalamic volume, we conducted Mendelian randomization (MR) analyses. Mediation analysis was further performed to assess the role of gut microbiota composition in this association.

RESULTS

Compared to HCs, migraine patients exhibited significantly reduced total hypothalamic volume (813.53 ± 66.46 mm³ vs. 831.86 ± 57.91 mm³; FDR q = 0.048) and inferior tuberal hypothalamic volume (255.26 ± 30.17 mm³ vs. 265.29 ± 23.32 mm³; FDR q = 0.046). These reductions were particularly pronounced in patients with CM, whereas no significant differences were observed in those with EM. MR analysis revealed causal effects of total hypothalamic volumes (OR = 0.80, FDR q = 7.28 × 10-5) and inferior tuberal hypothalamic volumes (OR = 0.85, FDR q = 2.61 × 10-2) on migraine, providing causal evidence to support the observational findings from the cross-sectional study. Furthermore, specific gut microbiome (genus DefluviitaleaceaeUCG011, genus Eubacteriumruminantiumgroup, and family FamilyXIII) were identified as partial mediators of the hypothalamus-migraine link (FDR q < 0.05).

CONCLUSIONS

This study suggests that atrophy of the inferior tuberal subregion of the hypothalamus plays a pivotal role in increasing migraine risk, and that this effect is partially mediated through alterations in gut microbiome composition.