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In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3\u03b2 (GSK3\u03b2), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The protein expression levels of phosphatidylinositol 4\u2010phosphate 5\u2010kinase type\u20101 gamma (PIP5K1C), phosphatidylinositol 4\u2010kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3\u03b2 were measured using enzyme\u2010linked immunosorbent assays and multiplex fluorescent bead\u2010based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3\u03b2, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3\u03b2 were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that the expression levels of Akt1\/GSK3\u03b2 and its upstream regulator PTEN are considerably altered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12409","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T03:59:38Z","timestamp":1705982378000},"page":"121-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Marked alteration of phosphoinositide signaling\u2010associated molecules in postmortem prefrontal cortex with bipolar 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