engleski

The role of COMT Val158met polymorphism in PTSD symptomatology

Prefrontal association cortex (PFC) plays an important role in moderating human behaviour, controlling emotions, cognitive and different executive functions. Exposure to stress impairs PFC functions and leads to reckless behaviour, loss of impulse control and the ability to focus attention, all characteristic symptoms of post- traumatic stress disorder (PTSD). Stress affects PFC function by increasing catecholamine release. Catechol-O- methyltransferase (COMT) is one of the enzymes that degrade catecholamine neurotransmitters. A common COMT polymorphism, rs4680 (Val158Met), plays an important role in cortical dopamine degradation by affecting COMT enzyme activity. The valine (Val) variant of the COMT Val158Met has been associated with greater dopamine degradation and less synaptic dopamine, compared to the methionine (Met) variant. The COMT Met/Met genotype has been associated with more efficient PFC activation and better cognitive performance. The study included 455 male war veterans (303 smokers and 152 non- smokers) with current and chronic combat- related PTSD. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the structure and severity of symptoms in PTSD patients. We assessed three original PANSS subscales (positive, negative and general psychopathology subscales), and additional PANSS derived subscales (excitement, cognitive, psychotic and depressive subscales). Genotyping of the COMT Val158Met polymorphism was performed with TaqMan Drug Metabolism Genotyping Assay. Results showed a significant difference in PANSS total (P=0.027) scores between smokers and nonsmokers which could be explained by the self-medication hypothesis. Therefore, all further analyses were done separately for smokers and non-smokers. Opposed to the lack of any association in smokers, significant differences were found between different COMT genotype carriers and the PANSS total (P=0.046), PANSS cognitive (P=0.014), PANSS excitement (P=0.013) and PANSS psychotic (P=0.023) subscale scores in non- smokers. The observed differences were due to the more severe symptoms found in Val/Val carriers than in other genotype carriers. These results were confirmed after comparing non- smokers who were Val allele carries to the Met/Met homozygotes. Higher PANSS total (P=0.017), PANSS cognitive (P=0.015), PANSS excitement (P=0.003) and PANSS psychotic (P=0.006) subscale scores in Val allele carriers compared to Met/Met carriers were detected. These results indicate that COMT Val allele, associated with lower dopamine availability, could contribute to the more severe PTSD symptomatology (including cognitive, psychotic, depressive and mania-like excitement symptoms). These data support the hypothesis that lower dopamine availability, seen in Val allele carriers, leads to reduced hippocampal volume after traumatic exposure and consequently more severe symptoms in PTSD.

PTSD ; COMT ; gene polymorphism ; symptomatology

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