Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis

Background: Psychosis is common in bipolar disorder (BD) and is related to more severe cognitive impairments. Since the molecular mechanism of BD psychosis is elusive, we conducted this study to explore the proteomic differences associated with BD psychosis in the dorsolateral prefrontal cortex (DLPFC; BA9). Methods: Postmortem DLPFC gray matter tissues from five pairs of age-matched male BD subjects with and without psychosis history were used. Tissue proteomes were identified and quantified by label-free liquid chromatography tandem mass spectrometry and then compared between groups. Statistical significance was set at q < 0.40 and Log₂ fold change (Log₂FC) ≥ |1|. Protein groups with differential expression between groups at p < 0.05 were subjected to pathway analysis. Results: Eleven protein groups differed significantly between groups, including the reduction of tenascin C (q = 0.005, Log₂FC = −1.78), the elevations of synaptoporin (q = 0.235, Log₂FC = 1.17) and brain-specific angiogenesis inhibitor 1-associated protein 3 (q = 0.241, Log₂FC = 2.10) in BD with psychosis. The between-group differences of these proteins were confirmed by Western blots. The top enriched pathways (p < 0.05 with ≥ 3 hits) were the outgrowth of neurons, neuronal cell proliferation, growth of neurites, and outgrowth of neurites, which were all predicted to be upregulated in BD with psychosis. Limitations: Small sample size and uncertain relationships of the observed proteomic differences with illness stage and acute psychosis. Conclusions: These results suggested BD with psychosis history may be associated with abnormalities in neurodevelopment, neuroplasticity, neurotransmission, and neuromodulation in the DLPFC.