Catechol-O-Methyltransferase Val158Met Polymorphism and Antisaccade Eye Movements in Schizophrenia

Abstract

The catechol-O-methyltransferase (COMT) enzyme catabolizes dopamine. The val(158)met single nucleotide polymorphism (rs4680) in the COMT gene has received considerable attention as a candidate gene for schizophrenia as well as for frontally mediated cognitive functions. Antisaccade performance is a good measure of frontal lobe integrity. Deficits on the task are considered a trait marker for schizophrenia. The aim of this study was to investigate the association of COMT val(158)met polymorphism with antisaccade eye movements in schizophrenia patients and healthy controls. Schizophrenia patients (N = 105) and healthy controls (N = 95) underwent infrared oculographic assessment of antisaccades. Subjects were genotyped for COMT val(158)met and divided into 3 groups according to genotype (val/val, val/met, and met/met). Patients displayed significantly more reflexive errors, longer and more variable latency, and lower amplitude gain than controls (all P < 0.02). A greater number of val(158) alleles was associated with shorter (P = 0.045) and less variable (P = 0.028) antisaccade latency and, nonsignificantly, with lower reflexive error rate (P = 0.056). None of these variables showed a group-by-genotype interaction (P > 0.1). There were no significant associations of genotype with measures of amplitude gain or spatial error (P > 0.2). The results suggest that COMT val(158) carrier status is associated with better performance on the antisaccade task. Possible explanations of this finding are discussed.

Electrophysiological Endophenotypes for Schizophrenia

“…48 Other genes have been found to be associated with AS performance, including the gene encoding the regulator of G-protein signaling subtype 4 ( RGS4 ) 119 and COMT. 120 However, the pedigree-based COGS study did not find these effects. 48 …”

Eye movement dysfunction in first-degree relatives of patients with schizophrenia: A meta-analytic evaluation of candidate endophenotypes

“…One of the primary reasons that EMD has been of such interest is that several lines of evidence converge in support of a genetic influence on EMD, thereby implying that EMD will assist in gene identification. Indeed, a small number of molecular genetics studies have provided promising preliminary evidence in support of a relationship between EMD and particular genes (Ettinger et al, 2008; Haraldsson et al, 2008; Rybakowski & Borkowska, 2002; Rybakowski, Borkowska, Czerski, & Hauser, 2001; Thaker, Wonodi, Avila, Hong, & Stine, 2004) or chromosomal regions (Arolt et al, 1996; Arolt et al, 1999; Matthysse et al, 2004; Myles-Worsley et al, 1999). While these studies are important in their attempts to investigate the genetic underpinnings of EMD, they are few, difficult to replicate, typically employ small samples, cover few of the different forms of EMD that have been implicated in schizophrenia, and give us little to go on when faced with how to evaluate the candidacy of different aspects of EMD as endophenotypes.…”

The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults

“…Thaker et al (2004) showed an advantage in predictive pursuit for healthy Met allele homozygotes and found 10% of variance in the gain parameter to be explained by the COMT genotype. In contrast, Haraldsson et al (2010) failed to find a significant association in a similar study. However, they measured pursuit on continuous waveform motion without target blanking, so extraretinal processes might have been insufficiently prominent.…”

“…Some findings point to functional associations with antisaccade performance (Ettinger et al, 2008; Haraldsson et al, 2010; Kasparbauer et al, 2015), but differences foremost showed up in BOLD responses. Smooth pursuit seems ideal for studying different mechanisms involved in oculomotor control, because it relies on a sophisticated interplay between motion perception, sensorimotor transformation, and anticipatory abilities (Lisberger, 2010; Kowler et al, 2014).…”