Reproductive-state dependent changes in inner ear gene expression in female plainfin midshipman fish.

Twin and family studies estimate the heritability of bipolar disorder (BD) at 60%–80% [, ], and genome‐wide association studies indicate that common genetic variants account for around 20% of BD phenotypic variance []. However, the specific biological mechanisms involved in the pathophysiology of BD remain poorly understood. Additionally, the inaccessibility of living brain tissue and the lack of suitable in vitro and in vivo models make donor‐derived induced pluripotent stem cells (iPSCs) an attractive tool for studying fundamental cellular processes in human brain cells that preserve the genetic background of the donors. The advent of induced pluripotent stem cell (iPSC) technology has revolutionised neuropsychiatric research by enabling the generation of patient‐derived brain cells. These models provide direct access to living human brain cells, allowing the study of early neurodevelopmental processes, cellular excitability, and drug responsiveness in a controlled in vitro setting and comparison to control cells. iPSC‐derived neurons have been vital in identifying alterations in neurodevelopmental trajectories, hyperexcitability and disrupted neuroplasticity [, , ], all of which are implicated in BD pathophysiology. Moreover, these models facilitate the investigation of pharmacological interventions, including treatment responsiveness, offering a robust platform for hypothesis generation and precision medicine approaches in BD. In this study, we aim to investigate the transcriptional changes associated with BD using an in vitro model of iPSC‐derived neurons and astrocytes in conjunction with whole transcriptome sequencing to uncover novel molecular mechanisms that contribute to the pathophysiology of BD.