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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 (DLP...

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Autores principales: Ho, Ada M.-C., Cabello-Arreola, Alejandra, Markota, Matej, Heppelmann, Carrie J., Charlesworth, M. Cristine, Ozerdem, Aysegul, Mahajan, Gouri, Rajkowska, Grazyna, Stockmeier, Craig A., Frye, Mark A., Choi, Doo-Sup, Veldic, Marin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234814/
https://www.ncbi.nlm.nih.gov/pubmed/32339108
http://dx.doi.org/10.1016/j.jad.2020.03.105
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author Ho, Ada M.-C.
Cabello-Arreola, Alejandra
Markota, Matej
Heppelmann, Carrie J.
Charlesworth, M. Cristine
Ozerdem, Aysegul
Mahajan, Gouri
Rajkowska, Grazyna
Stockmeier, Craig A.
Frye, Mark A.
Choi, Doo-Sup
Veldic, Marin
author_facet Ho, Ada M.-C.
Cabello-Arreola, Alejandra
Markota, Matej
Heppelmann, Carrie J.
Charlesworth, M. Cristine
Ozerdem, Aysegul
Mahajan, Gouri
Rajkowska, Grazyna
Stockmeier, Craig A.
Frye, Mark A.
Choi, Doo-Sup
Veldic, Marin
author_sort Ho, Ada M.-C.
collection PubMed
description 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 Log(2) fold change (Log(2)FC) ≥ |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, Log(2)FC = −1.78), the elevations of synaptoporin (q = 0.235, Log(2)FC = 1.17) and brain-specific angiogenesis inhibitor 1-associated protein 3 (q = 0.241, Log(2)FC = 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.
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spelling pubmed-72348142021-06-01 Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis Ho, Ada M.-C. Cabello-Arreola, Alejandra Markota, Matej Heppelmann, Carrie J. Charlesworth, M. Cristine Ozerdem, Aysegul Mahajan, Gouri Rajkowska, Grazyna Stockmeier, Craig A. Frye, Mark A. Choi, Doo-Sup Veldic, Marin J Affect Disord Article 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 Log(2) fold change (Log(2)FC) ≥ |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, Log(2)FC = −1.78), the elevations of synaptoporin (q = 0.235, Log(2)FC = 1.17) and brain-specific angiogenesis inhibitor 1-associated protein 3 (q = 0.241, Log(2)FC = 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. 2020-04-08 2020-06-01 /pmc/articles/PMC7234814/ /pubmed/32339108 http://dx.doi.org/10.1016/j.jad.2020.03.105 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ho, Ada M.-C.
Cabello-Arreola, Alejandra
Markota, Matej
Heppelmann, Carrie J.
Charlesworth, M. Cristine
Ozerdem, Aysegul
Mahajan, Gouri
Rajkowska, Grazyna
Stockmeier, Craig A.
Frye, Mark A.
Choi, Doo-Sup
Veldic, Marin
Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
title Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
title_full Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
title_fullStr Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
title_full_unstemmed Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
title_short Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
title_sort label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234814/
https://www.ncbi.nlm.nih.gov/pubmed/32339108
http://dx.doi.org/10.1016/j.jad.2020.03.105
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