Associations between neuroticism items and risk of bipolar disorder: a causal perspective

In observational studies, a significant association between neurotic personality and bipolar disorder (BD) has been observed, but it remains unclear. Additionally, current genetic studies have primarily utilized a sum score of psychological traits, only focusing on variants that affect the majority of aggregated items. Here, we aim to leverage recent large-scale genome-wide association studies (GWAS) to investigate the causal connection between neuroticism items and BD. This study employs Mendelian randomization to investigate the bidirectional association between specific items used to measure the neuroticism and BD. Neuroticism items' genome-wide association study (GWAS) data were obtained from the EBI database, while BD GWAS data were sourced from the Psychiatric Genomics Consortium (PGC). The main analytical method in this study was inverse variance weighted (IVW) method. Our findings indicating that specific neuroticism items (feeling tense, feeling hurt, and feeling lonely) have a potential association with BD. Additionally, individuals often exhibit changes in personality after developing the disease, becoming more prone to feeling tense, hurt, and experiencing emotional fluctuations. Overall, our research provides evidence of a bidirectional relationship between neuroticism items and BD. These findings highlight the genetic complexity of BD, which may be influenced by the genetic structure of individual neuroticism subscale items. It also uncovering the biological basis behind complex psychological and behavioral traits, and providing new perspectives and methods for clinical interventions and treatments.