No 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.

Objective Cognitive dysfunction in fibromyalgia has become a key symptom considered by patients as more disabling than pain itself. Experimental evidence from neuropsychological and neuroimaging studies indicates that such cognitive impairments are especially robust when patients need to set in motion working memory processes, suggesting the existence of an altered functioning underlying the cerebral cortices of the frontoparietal memory network. However, the temporal dynamics of working memory sub-processes have not yet been explored in fibromyalgia. Subjects Thirty-six right-handed women participated in the experiment: comprising eighteen patients with fibromyalgia and eighteen healthy controls. Methods Event-related potentials (ERPs) and behavioural responses were recorded while participants were engaged in a 2-back working memory task. Principal Component Analyses (PCA) were used to define and quantify the ERP components associated with working memory processes. Results Fibromyalgia patients exhibited worse performance than the control group, as revealed by their number of errors in the working memory task. Moreover, both scalp parieto-occipital P2 and parieto-occipital P3 amplitudes were lower for patients than for healthy control participants. Regression analyses revealed that lower P3 amplitudes were observed in those patients with fibromyalgia reporting higher pain ratings. Conclusions Current results suggest that both encoding of information (as reflected by P2) and subsequently, context updating and the replacement (as seen in lower P3 amplitudes), as a part of working memory sub-processes, are impaired in fibromyalgia. Studying the temporal dynamics of working memory using ERP methodology is a helpful approach to detect specific cognitive impaired mechanisms in this chronic pain syndrome. These new data could be used to develop more specific treatments adapted for each patient.

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.

Previous research has shown a consistent association among genetic factors, psychological symptoms and pain associated with fibromyalgia. However, how these symptoms interact to moderate genetic factors in fibromyalgia has rarely been studied to date. The present research investigates whether psychological symptoms can moderate the effects of catechol-O-methyltransferase on pain and fatigue. A total of 108 women diagnosed with fibromyalgia and 77 healthy control participants took part in the study. Pain, fatigue, and psychological symptoms (anxiety, depression, pain catastrophizing, fear of pain and fear of movement) were measured by self-report questionnaires. Two types of statistical analyses were performed; the first was undertaken to explore the influences of COMT genotypes on clinical symptoms by comparing patients with fibromyalgia and healthy controls. In the second analysis, moderation analyses to explore the role of psychological symptoms as potential factors that moderate the relationship between pain/fatigue and COMT genotypes were performed. The main results indicated that patients carrying the Met/Met genotype reported significantly higher levels of fatigue than heterozygote carriers (i.e., Met/Val genotype) and higher levels of fatigue, but not significantly different, than Val homozygote carriers. Among patients with fibromyalgia carrying methionine alleles (i.e., Met/Met + Met/Val carriers), only those who scored high on medical fear of pain, experienced an intensified feeling of fatigue. Thus, the present research suggests that fear of pain, as a psychological symptom frequently described in fibromyalgia may act as a moderating factor in the relationship between the Met allele of the COMT gene and the increase or decrease in self-reported fatigue. Although further research with wider patient samples is needed to confirm the present findings, these results point out that the use of psychological interventions focused on affective symptomatology might be a useful tool to reduce the severity of fibromyalgia.