Exploring the causal relationship between bipolar disorders and sensory, motor, and behavioral disorders: A bidirectional Mendelian randomization analysis

Medicine (Baltimore). 2025 Aug 22;104(34):e44056. doi: 10.1097/MD.0000000000044056.

ABSTRACT

The interrelationships between bipolar disorder (BD) and sensory, motor, and behavioral disorders are intricate and not well defined. While observational studies indicate potential associations, causal relationships have not been established. This study applies bidirectional Mendelian randomization (MR) analysis to examine potential causal links between BD and these disorders. Bidirectional MR analysis uses summary-level data from genome-wide association studies (GWAS). Genetic instruments are selected according to stringent significance thresholds and linkage disequilibrium (LD) criteria. The primary analytical approaches include inverse-variance weighted (IVW) MR and MR-Egger regression. Instrument strength is assessed using F-statistics. Significant bidirectional associations are identified. BD is associated with increased genetic susceptibility to pruritus (OR = 1.29, 95% CI: 1.06-1.57), small fiber neuropathy (OR = 1.64, 95% CI: 1.03-2.61), hyperkinetic disorders (OR = 2.02, 95% CI: 1.26-3.23), anorexia nervosa (OR = 1.19, 95% CI: 1.01-1.40), and autism spectrum disorder (OR = 1.10, 95% CI: 1.01-1.20). Conversely, pruritus and psoriasis are identified as significant genetic risk factors for BD (pruritus: OR = 1.04, 95% CI: 1.01-1.08; psoriasis: OR = 9.97, 95% CI: 1.85-53.67). Motor disorders are associated with a protective effect against BD (OR = 0.88, 95% CI: 0.80-0.96). This study demonstrates significant bidirectional causal associations between BD and sensory, motor, and behavioral disorders, underscoring the importance of early screening and integrated clinical management. Shared genetic and neurobiological mechanisms may inform the development of targeted interventions and therapeutic strategies.

PMID:40859500 | DOI:10.1097/MD.0000000000044056