To the best of our

To the best of our knowledge, this is the first association study to analyze COMT Val158/108Met and the ROCF immediate and delayed scores in veterans with PTSD. The significant difference in ROCF immediate and delayed scores was detected between different COMT Val158/108Met genotype groups in veterans with PTSD, but not in control subjects. This result confirms the significant relationship between COMT Val158/108Met variants and working memory in PTSD, and not between COMT Val158/108Met polymorphism and diagnosis of the PTSD itself, since COMT Val158/108Met genotype distribution did not differ between veterans with PTSD and control subjects. This is in line with data showing that COMT Val158/108Met polymorphism was not significantly associated with diagnosis of PTSD [19]. However, the literature data on this topic are inconsistent. The presence of the COMT Met/Met genotype significantly increased the risk of developing PTSD regardless of the severity of traumatic load [20]. Either Met/Met or Val/Val genotype was associated with more severe PTSD symptomatology [21]. Carriers of the Met allele had better functional outcome but lower rate of PTSD following mild traumatic Alda 1 injury [22]. However, the Met allele was also related to higher rate of PTSD after exposure to urban violence [23]. Nevertheless, the recent meta-analysis confirmed that COMT Val158/108Met was not significantly associated with PTSD [19]. The data regarding the association between COMT Val158/108Met and cognitive function are divergent [10,11,12,22,24,25,26,27,28]. Better performance on the ROCF immediate and delayed recall test among veterans with PTSD who were Met carriers, compared to Val/Val homozygotes, agrees with findings showing that carriers of the Val/Val genotype with PTSD frequently had more reductions in hippocampal volume [12] and worse memory retrieval [24] than Met carriers. It was also shown that PTSD subjects with Val/Val genotype had reduced functional connectivity between the hippocampus and prefrontal cortex during memory encoding-related activation patterns than Met carriers [25]. These differences in cognitive performance in carriers of different COMT genotypes might be due to the cortical hypodopaminergia in carriers of the Val/Val genotype, associated with worse cognitive performance, and deficits in executive and working memory functions [26]. All these findings might be explained with the lower dopamine availability in Val/Val carriers, suggesting an interaction between traumatic experience, lower dopamine and atrophy of the hippocampal and prefrontal regions, leading to the development and maintenance of PTSD and memory deficits in PTSD [12]. In contrast, Val/Val genotype carriers showed higher hippocampal activation after exposure to childhood trauma, which correlated with less PTSD symptoms and more trait resilience [27]. Regardless of the differences in traumatic experiences, these data suggest that COMT Val158/108Met might moderate the effect of traumatic stress on hippocampal function and subsequent development of resilience to psychopathology.