Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Ho AM

PROVIDER: S-EPMC7234814 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Ho Ada M-C AM Cabello-Arreola Alejandra A Markota Matej M Heppelmann Carrie J CJ Charlesworth M Cristine MC Ozerdem Aysegul A Mahajan Gouri G Rajkowska Grazyna G Stockmeier Craig A CA Frye Mark A MA Choi Doo-Sup DS Veldic Marin M

Journal of affective disorders 20200408

<h4>Background</h4>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).<h4>Methods</h4>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 ...[more]

PMID: 32339108

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Project description:Dorsolateral prefrontal cortex (DLPFC) and temporal pole (TP) are brain regions that display abnormalities in bipolar disorder (BD) patients. DNA methylation - an epigenetic mechanism both heritable and sensitive to the environment - may be involved in the pathophysiology of BD. To study BD-associated DNA methylomic differences in these brain regions, we extracted genomic DNA from the postmortem tissues of Brodmann Area (BA) 9 (DLPFC) and BA38 (TP) gray matter from 20 BD, ten major depression (MDD), and ten control age-and-sex-matched subjects. Genome-wide methylation levels were measured using the 850 K Illumina MethylationEPIC BeadChip. We detected striking differences between cortical regions, with greater numbers of between-brain-region differentially methylated positions (DMPs; i.e., CpG sites) in all groups, most pronounced in the BD group, and with substantial overlap across groups. The genes of DMPs common to both BD and MDD (hypothetically associated with their common features such as depression) and those distinct to BD (hypothetically associated with BD-specific features such as mania) were enriched in pathways involved in neurodevelopment including axon guidance. Pathways enriched only in the BD-MDD shared list pointed to GABAergic dysregulation, while those enriched in the BD-only list suggested glutamatergic dysregulation and greater impact on synaptogenesis and synaptic plasticity. We further detected group-specific between-brain-region gene expression differences in ODC1, CALY, GALNT2, and GABRD, which contained significant between-brain-region DMPs. In each brain region, no significant DMPs or differentially methylated regions (DMRs) were found between diagnostic groups. In summary, the methylation differences between DLPFC and TP may provide molecular targets for further investigations of genetic and environmental vulnerabilities associated with both unique and common features of various mood disorders and suggest directions of future development of individualized treatment strategies.

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Dataset Information

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

Background

Methods

Results

Limitations

Conclusions

Publications

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

Similar Datasets

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