Effects of COMT Genotypes on Working Memory Performance in Fibromyalgia Patients

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.

Working Memory Performance, Pain and Associated Clinical Variables in Women With Fibromyalgia

“…Patients with FM seem to preserve their WM span and ability to maintain and manipulate information for both visuospatial and verbal domains, as indicated by the span scores on the Digit Backward and Spatial Backward tasks, but the percentage of FM patients impaired for the ACT task at 36 s, related to short-term memory, divided attention, and information processing capacity, reached the 36.43%. Findings are in line with previous studies reporting cognitive deficits in different areas of memory, such as short-term ( Leavitt and Katz, 2006 ; Roldán-Tapia et al, 2007 ; Gelonch et al, 2018 ), long-term ( Park et al, 2001 ; Roldán-Tapia et al, 2007 ; Tesio et al, 2014 ), and working-memory ( Park et al, 2001 ; Dick et al, 2008 ; Cánovas et al, 2009 ; Kim et al, 2011 ; Seo et al, 2012 ; Tesio et al, 2014 ; Coppieters et al, 2015 ; Gelonch et al, 2018 ; Pidal-Miranda et al, 2018 ; Ferrera et al, 2020 ); however, they contrast with other studies that did not found altered information processing in patients with FM ( Park et al, 2001 ). This discrepancy could be explained by the fact that WM performance is particularly affected in those tasks that entail a higher workload ( Khaksari et al, 2019 ).…”

“…Likewise, lack of differences between patients with high and low pain threshold in any of the WM tasks does not support the hypothesis of an overlap between pain and cognition networks as an explanation for the cognitive dysfunction in FM ( Buhle and Wager, 2010 ; Schmidt-Wilcke et al, 2014 ; Sturgeon et al, 2015 ). Previous studies reported morphological ( Luerding et al, 2008 ; Cánovas et al, 2009 ; Robinson et al, 2011 ; Ceko et al, 2012 ), functional ( Napadow et al, 2010 ; Glass et al, 2011 ; Seo et al, 2012 ; Schmidt-Wilcke et al, 2014 ; González-Villar et al, 2017 ) and neurotransmission alterations in the dopaminergic ( Albrecht et al, 2015 ; Ferrera et al, 2020 ), glutamatergic and GABAergic systems ( De Paepe et al, 2020 ), which could be associated with pain in patients with FM. Future studies should clarify whether the WM functioning in FM can be explained by pain-mediated structural and functional neural reconfiguration.…”

Fear of pain moderates the relationship between self-reported fatigue and methionine allele of catechol-O-methyltransferase gene in patients with fibromyalgia

“…Finally, the possible effect of medication on clinical symptoms (i.e., pain, fatigue, depression, anxiety, fear of pain, fear of movement and pain catastrophizing) within the fibromyalgia group was tested using one-way ANOVA, including patients using and not using particular medications using a previously reported method [ 51 , 52 ]. These control analyses were conducted including analgesics, benzodiazepines and antidepressants, as factors.…”

Mejora de la velocidad de procesamiento en pacientes con fibromialgia: diseño y aplicación de un programa de intervención cognitiva

“…Asimismo, la aplicación de estimulación cognitiva a pacientes con daño cerebral adquirido ha mostrado una mejora en procesos como la VPI, la atención selectiva, o la velocidad de lectura, después de varias sesiones de entrenamiento cognitivo computarizado (Sturm & Willmes, 1991;Wilson & Robertson, 1992). Adicionalmente, debido a su localización y distribución cerebral, así como a su estrecha relación con el resto de procesos cognitivos (Posthuma & de Geus, 2008;Ríos et al, 2004), la mejora de la VPI, podría repercutir directamente sobre procesos como la memoria de trabajo (Duval et al, 2008) o el procesamiento atencional (Sturm & Willmes, 1991), procesos clínicamente alterados en fibromialgia (Ferrera et al, 2020;Mercado et al, 2021)the COMT gene. Además, varias investigaciones han puesto de manifiesto una relación consistente entre la VPI y el desempeño funcional en las actividades de la vida diaria (Ball et al, 2007).…”

“…Principalmente, se han observado comorbilidades afectivas como elevados niveles de ansiedad y/o depresión (Fietta et al, 2007;Galvez-Sánchez et al, 2018), así como déficits cognitivos en distintos dominios, tales como la atención, la memoria y las funciones ejecutivas (Bell et al, 2018;Ferrera et al, 2020;Wu et al, 2018).…”