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  • Since cognitive disturbances are core features

    2020-07-23

    Since cognitive disturbances are core features of PTSD [3,4], and in some studies COMT Val158/108Met was associated with cognition [10] and hippocampal volume [12], the hypothesis was that carriers of the Met allele will show better cognitive performance compared to Val/Val carriers in PTSD. The aim of this study was to assess 400 the differences in cognitive functioning between PTSD and control subjects and to evaluate the association between COMT Val158/108Met polymorphism and cognitive function measured by the ROCF in Caucasian veterans with combat related PTSD.
    Materials and methods
    Discussion The main findings of this study are: 1) the ROCF immediate and delayed test scores, but not the ROCF copy test scores, were influenced by the diagnosis of PTSD; 2) frequency of the COMT Val158/108Met genotypes did not differ between veterans with PTSD and control subjects; 3) COMT Val158/108Met was significantly associated with the ROCF immediate and delayed scores in veterans with PTSD, but not in control subjects; and 4) within veterans with PTSD, Met carriers performed better (i.e. had higher ROCF scores) than Val/Val homozygotes on both ROCF immediate recall and delayed recall test. Control subjects performed better on the ROCF immediate and delayed tests than PTSD subjects. Worse results on the ROCF immediate and delayed tests in veterans with PTSD corroborate with cognitive disturbances in PTSD [14], and agree with previous preliminary results obtained on a different, but much smaller group of Croatian war veterans with PTSD [15]. Impaired working memory in PTSD [4] is consistent with the significantly lower performance on measures of learning, immediate and delayed verbal memory [14], and reduced verbal and visual working memory [16] in veterans with PTSD. Even special operations warfighters, who were exposed to acute military stress, but did not have a diagnosis of PTSD, showed impaired working memory and poor ROCF copy and recall performance after exposure to the realistic levels of acute (i.e. interrogation) stress [17]. Acute stress conditions incapacitated warfighters to copy and recall information and also diminished working memory, a cognitive function important in military service as soldiers need to rapidly reveal, retain and manipulate new information needed for executive cognitive operations [17]. In 400 to these conditions [17], where subjects were evaluated 15 min after exposure to a high acute stress, in our study all subjects were evaluated years after trauma. In addition, 6 h after this form of acute stress, all special operations warfighters had normal ROCF copy and recall performances [17], which agrees with our data obtained in healthy subjects. Since in a previous study, age, gender, and IQ affected the results of the ROCF [18], in this study, the ROCF scores were controlled for these variables. The possible influence of gender on the ROCF was excluded since only male subjects were included in the study. In contrast to data obtained in normal volunteers [18], but in agreement with data in drug naïve subjects with PTSD [14], measures of immediate and delayed recall of verbal and visual explicit memory material were not affected by different IQ or years of education. In addition, our study revealed a lack of significant effect of smoking and age on the ROCF results. Our results are confirmed by the previous studies [[14],14], showing that memory deficits, especially impaired working memory, are related to PTSD. Recent meta-analysis confirmed impairments in verbal learning and memory, speed of processing, and attention/working memory, suggesting that therapeutic strategies should focus on improving these neurocognitive dysfunctions in PTSD [4]. 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 brain 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].