Causal relationship between bulimia nervosa and microstructural white matter: evidence from Mendelian randomization

TL;DR

This study finds a causal link between bulimia nervosa and changes in brain white matter structure using genetic data.

Contribution

It provides the first causal evidence that bulimia nervosa affects white matter microstructure.

Findings

BN causally affects nine white matter tracts, including brainstem and emotion-related pathways.

The effects include sensory and emotional processing tracts, which may explain symptoms in BN patients.

Findings extend observational associations to a causal relationship using Mendelian randomization.

Abstract

Observational studies suggest white matter (WM) microstructural anomalies are linked to bulimia nervosa (BN), but a direct causal relationship remains unestablished. This study aimed to investigate the causal impact of BN on WM microstructure.

We analyzed genome-wide association study (GWAS) summary data from 2442 individuals to identify genetically predicted BN. Diffusion MRI were obtained from the UK Biobank. After assessing instrumental variable validity, we conducted Mendelian randomization (MR) using inverse variance weighting (IVW) as the primary method, followed by pleiotropy and heterogeneity tests.

The MR analysis from BN to brain imaging-derived phenotypes showed that BN had significant causal effects on a union set of nine tracts (including a total of 18 image-derived phenotypes) (IVW, P < 0.05): brainstem tracts (pontine crossing tract, bilateral medial lemniscus, left superior cerebellar peduncle, and middle cerebellar peduncle), sensory-related tracts (right retrolenticular part of the internal capsule and left inferior longitudinal fasciculus), and emotion-related tracts (left anterior corona radiata and right cingulum hippocampus).

This study revealed that BN has a causal effect on WM microstructure, which extends the reports of association to causation for WM and BN. These causal effects may explain the deficits in feeding, taste, vision, and emotion regulation that are often observed in patients with BN.

Level of evidence III well-designed cohort analytic study.

The online version contains supplementary material available at 10.1007/s40519-025-01754-z.

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