Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics
John Kelsoe1, Anna Ou1, Sara Rosenthal
1University of California San Diego.
Research Square
|October 27, 2023
Summary
Lithium response in bipolar disorder (BD) may involve neuronal growth cone and PI3K-Akt signaling pathways. This study replicated previous findings, highlighting these pathways but not extracellular matrix proteins, for better treatment prediction.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Lithium is a primary treatment for bipolar disorder (BD), but its mechanism of action and treatment outcome predictors remain unclear.
- Previous multi-omics research linked focal adhesion, extracellular matrix (ECM), and PI3K-Akt signaling to lithium response.
Approach:
- Network propagation methods were applied to a genome-wide association study of 2,039 independent bipolar disorder patients from the International Consortium on Lithium Genetics (ConLiGen).
- Functional enrichment analysis was performed to validate previous findings and identify key biological pathways associated with lithium response.
Key Points:
- Replication of previous findings confirmed the association of focal adhesion and PI3K-Akt signaling pathways with lithium response in bipolar disorder.
- The extracellular matrix (ECM) pathway was not found to be significantly associated with lithium response in this independent cohort.
- Results suggest that neuronal growth cone function and PI3K-Akt signaling are implicated in lithium treatment outcomes.
Conclusions:
- Deficits in neuronal growth cone and PI3K-Akt signaling pathways may influence lithium response in bipolar disorder patients.
- Extracellular matrix proteins do not appear to be a significant factor in lithium response.
- These findings contribute to a better understanding of lithium's mechanism of action and may aid in predicting treatment outcomes.
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