Abstract
Growing research has reported the presence of a clear impairment of working memory functioning in fibromyalgia. Although different genetic factors involving dopamine availability (i.e, the COMT gene) have been associated with the more severe presentation of key symptoms in fibromyalgia, scientific evidence regarding the influence of COMT genotypes on cognitive impairment in these patients is still lacking. To this end, 167 participants took part in the present investigation. Working memory performance was assessed by the application of the SST (Spatial Span Test) and LNST (Letter and Number Sequence Test) belonging to the Weschler Memory Scale III. Significant working memory impairment was shown by the fibromyalgia patients. Remarkably, our results suggest that performance according to different working memory measures might be influenced by different genotypes of the COMT gene. Specifically, fibromyalgia patients carrying the Val/Val genotype exhibited significantly worse outcomes for the span of SST backward, SST backward score, SST total score and the Working Memory Index (WMI) than the Val/Val healthy carriers. Furthermore, the Val/Val patients performed worse on the SST backward and SST score than heterozygotes. Our findings are the first to show a link between the COMT gene and working memory dysfunction in fibromyalgia, supporting the idea that higher COMT enzyme activity would contribute to more severe working memory impairment in fibromyalgia.
Highlights
Neurobiological evidence gathered from the past decade has established that dopamine plays a crucial role in neurotransmission mechanisms supporting mental operations involved in working memory processing [1,2,3,4,5,6,7,8,9]
Statistical data related to the genotype and allele frequency distributions of the COMT gene considering each group of participants are displayed in the Table 2
We found a significant difference for the fibromyalgia group between those patients carrying the Val/Val and Met/Val genotypes (p = 0.03 for the Span Test (SST) backward score and p = 0.014 for the SST total score)
Summary
Neurobiological evidence gathered from the past decade has established that dopamine plays a crucial role in neurotransmission mechanisms supporting mental operations involved in working memory processing [1,2,3,4,5,6,7,8,9]. It has been reported that those subjects carrying Met alleles showed better functioning in verbal and visuo-spatial working memory tasks [28,30,34], and fewer perseverative errors on the Wisconsin Card Sorting Test (WCST) than Val carriers [35,36] These data seem to have a neurophysiological correlate, since brain imaging studies have shown that Val carriers exhibited a decrease in dopamine levels within the PFC, reducing the blood-oxygen-level dependent (BOLD) response of this brain region compared to that in the Met carriers [31,36], and reflected by the poor performance of Val carriers in working memory tests [29]. These results have been replicated in chronic patients, such as those suffering from posttraumatic stress disorder or schizophrenia [36,37,38,39], leading to the consideration of this gene as a therapeutic target for improving cognitive symptoms [40]
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