Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

Transl Psychiatry. 2024 Feb 23;14(1):109. doi: 10.1038/s41398-024-02811-4.


Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

MeSH terms

  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / genetics
  • Focal Adhesions
  • Genome-Wide Association Study
  • Humans
  • Lithium* / pharmacology
  • Lithium* / therapeutic use
  • Multiomics
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics


  • Lithium
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases