Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex

Hikaru Takeuchi, Ryosuke Kimura, Hiroaki Tomita, Yasuyuki Taki, Yoshie Kikuchi, Chiaki Ono, Zhiqian Yu, Izumi Matsudaira, Rui Nouchi, Ryoichi Yokoyama, Yuka Kotozaki, Seishu Nakagawa, Sugiko Hanawa, Kunio Iizuka, Atsushi Sekiguchi, Tsuyoshi Araki, Carlos Makoto Miyauchi, Shigeyuki Ikeda, Kohei Sakaki, Kelssy H. KelssyTakayuki Nozawa, Susumu Yokota, Daniele Magistro, Tadashi Imanishi, Ryuta Kawashima

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.

Original languageEnglish
Pages (from-to)6028-6037
Number of pages10
JournalHuman Brain Mapping
Issue number18
Publication statusPublished - Dec 15 2021

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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