Abstract / Summary
Impulsivity has received limited attention in cluster headache (CH), despite growing evidence of a broader behavioral phenotype in the disorder. We aimed to compare impulsivity between patients with CH and healthy controls and to explore associations between selected candidate genetic variants and impulsivity measures. This prospective case–control genetic association study included 209 participants (113 patients with CH and 96 healthy controls), of whom 208 had Barratt Impulsiveness Scale (BIS-11) data. BIS-11 total and domain scores were analyzed using multivariable linear regression adjusted for age and sex. Seven candidate single-nucleotide polymorphisms (SNPs) were evaluated under additive, dominant, and recessive models adjusted for age, sex, and CH status. The 84 genotype–phenotype tests were exploratory, with Bonferroni and Benjamini–Hochberg false discovery rate correction. A sensitivity analysis examined BIS-11 scores by bout status in episodic CH. Patients with CH had higher BIS-11 total scores than controls after adjustment for age and sex (adjusted difference 11.68; 95% confidence interval (CI) 6.61–16.75; p = 9.5 × 10⁻⁶), as well as higher attentional (2.77; 95% CI 1.29–4.26; p = 2.96 × 10⁻⁴), motor (5.46; 95% CI 2.99–7.94; p = 2.17 × 10⁻⁵), and non-planning scores (3.44; 95% CI 1.05–5.84; p = 5.04 × 10⁻³). BIS-11 scores did not differ significantly between patients assessed during an active bout and those assessed during remission. Three nominal genotype–phenotype signals were identified: DRD1 rs686 with total BIS-11 score under the recessive model (β = 6.36; p = 4.85 × 10⁻²), GRIN2B rs1806201 with motor impulsivity under the recessive model (β = 4.43; p = 4.09 × 10⁻²), and DRD1 rs686 with non-planning impulsivity under the additive model (β = 1.57; p = 3.17 × 10⁻²). None remained statistically significant after multiple-testing correction. Patients with CH exhibited higher self-reported impulsivity across the BIS-11 total score and all three domains after adjustment for age and sex, supporting impulsivity as a relevant behavioral feature within the clinical phenotype of the disorder. The nominal DRD1 and GRIN2B genotype–phenotype signals require replication in larger, independent cohorts before any genetic contribution to impulsivity in CH can be established. Not applicable.