Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/genética , Regulación de la Expresión Génica , Metionina/genética , Polimorfismo de Nucleótido Simple/genética , Trastornos por Estrés Postraumático/sangre , Trastornos por Estrés Postraumático/genética , Valina/genética , Adolescente , Adulto , Campaña Afgana 2001- , Animales , Modelos Animales de Enfermedad , Femenino , Genotipo , Humanos , Guerra de Irak 2003-2011 , Masculino , Persona de Mediana Edad , Personal Militar , Escalas de Valoración Psiquiátrica , Ratas , Reflejo de Sobresalto , Trastornos por Estrés Postraumático/etiología , Adulto JovenAsunto(s)
Leucocitos/metabolismo , Acontecimientos que Cambian la Vida , Trastornos por Estrés Postraumático/genética , Estrés Psicológico/genética , Acortamiento del Telómero/genética , Adolescente , Adulto , Factores de Edad , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Trastornos por Estrés Postraumático/patología , Estrés Psicológico/patología , Adulto JovenRESUMEN
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.