@article{e2b323558e124c1cbfa622749e3540f2,
title = "Differential dorsolateral prefrontal cortex proteomic profiles of suicide victims with mood disorders",
abstract = "Suicide is a major public health concern; nevertheless, its neurobiology remains unknown. An area of interest in suicide research is the dorsolateral prefrontal cortex (DLPFC). We aimed to identify altered proteins and potential biological pathways in the DLPFC of individuals who died by suicide employing mass spectrometry-based untargeted proteomics. Postmortem DLPFC from age-matched male suicide mood disorder cases (n = 5) and non-suicide mood disorder cases (n = 5) were compared. The proteins that differed between groups at false discovery rate (FDR) adjusted pvalues (Benjamini–Hochberg–Yekutieli) <0.3 and Log2 fold change (FC) >|0.4| were considered statistically significant and were subjected to pathway analysis by Qiagen Ingenuity software. Thirty-three of the 5162 detected proteins showed significantly altered expression levels in the suicide cases and two of them after adjustment for body mass index. The top differentially expressed protein was potassium voltage-gated channel subfamily Q member 3 (KCNQ3) (Log2FC =-0.481, p = 2.10 × 10-09, FDR = 5.93 × 10-06), which also showed a trend to downregulation in Western blot (p = 0.045, Bonferroni adjusted p = 0.090). The most notably enriched pathway was the GABA receptor signaling pathway (p < 0.001). Here, we report a reduction trend of KCNQ3 levels in the DLPFC of male suicide victims with mood disorders. Further studies with a larger sample size and equal sex representation are needed.",
keywords = "Brain, DLPFC, GABA, KCNQ3, Mood disorders, Pathways, Proteomics, Suicide",
author = "Alejandra Cabello-Arreola and Ho, {Ada Man Choi} and Aysegul Ozerdem and Cuellar-Barboza, {Alfredo B.} and Kucuker, {Mehmet U.} and Heppelmann, {Carrie J.} and Charlesworth, {M. Cristine} and Deniz Ceylan and Stockmeier, {Craig A.} and Grazyna Rajkowska and Frye, {Mark A.} and Choi, {Doo Sup} and Marin Veldic",
note = "Funding Information: This research is supported by the Mayo Foundation for Medical Education and Research, the J. Willard and Alice S. Marriott Foundation, and the James D. and Pamela S. Deal family. The tissue bank is supported by the NIGMS Center for Psychiatric Neuroscience COBRE grant P30 GM103328 and NIMH grant R01 MH67996. We would also like to thank the Ulm Foundation and NIAAA grant AA018779 awarded to DSC. Acknowledgments: We deeply appreciate the invaluable contributions made by the next-of-kin of the deceased, the staff of the Cuyahoga County Medical Examiner's Office, Cleveland, OH, and the Mayo Clinic Medical Genome Facility Proteomics Core for providing the proteomic service. We also acknowledge the contributions of Drs. James Overholser, George Jurjus and Herbert Y. Meltzer, and of Lesa Dieter and Gouri Mahajan in psychiatric assessments and tissue dissection. Funding Information: Funding: This research is supported by the Mayo Foundation for Medical Education and Research, the J. Willard and Alice S. Marriott Foundation, and the James D. and Pamela S. Deal family. The tissue bank is supported by the NIGMS Center for Psychiatric Neuroscience COBRE grant P30 GM103328 and NIMH grant R01 MH67996. We would also like to thank the Ulm Foundation and NIAAA grant AA018779 awarded to DSC. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = mar,
doi = "10.3390/genes11030256",
language = "English (US)",
volume = "11",
journal = "Genes",
issn = "2073-4425",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",
}