title: Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD.
abstract: Posttraumatic stress disorder (PTSD), a trauma-related mental disorder, is associated with mitochondrial dysfunction in the brain. However, the biologic approach to identifying the mitochondria-focused genes underlying the pathogenesis of PTSD is still in its infancy. Previous research, using a human mitochondria-focused cDNA microarray (hMitChip3) found dysregulated mitochondria-focused genes present in postmortem brains of PTSD patients, indicating that those genes might be PTSD-related biomarkers. To further test this idea, this research examines profiles of mitochondria-focused gene expression in the stressed-rodent model (inescapable tail shock in rats), which shows characteristics of PTSD-like behaviors and also in the blood of subjects with PTSD. This study found that 34 mitochondria-focused genes being upregulated in stressed-rat amygdala. Ten common pathways, including fatty acid metabolism and peroxisome proliferator-activated receptors (PPAR) pathways were dysregulated in the amygdala of the stressed rats. Carnitine palmitoyltransferase 1B (CPT1B), an enzyme in the fatty acid metabolism and PPAR pathways, was significantly over-expressed in the amygdala (P < 0.007) and in the blood (P < 0.01) of stressed rats compared with non-stressed controls. In human subjects with (n = 28) or without PTSD (n = 31), significant over-expression of CPT1B in PTSD was also observed in the two common dysregulated pathways: fatty acid metabolism (P = 0.0027, false discovery rate (FDR) = 0.043) and PPAR (P = 0.006, FDR = 0.08). Quantitative real-time polymerase chain reaction validated the microarray findings and the CPT1B result. These findings indicate that blood can be used as a specimen in the search for PTSD biomarkers in fatty acid metabolism and PPAR pathways, and, in addition, that CPT1B may contribute to the pathology of PTSD.
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Benedek
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Fullerton
authors.affiliation: U.S. Army Pacific Command, Hawaiian Islands, HI, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Forsten
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Naifeh
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Benevides
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Le
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Smerin
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Russell
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ursano
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008889:Military Personnel; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; C542591:CPT1B protein, human; C000600281:CPT1b protein, rat; D002334:Carnitine O-Palmitoyltransferase