COMT genotype and response to cognitive remediation in schizophrenia

Abstract

Background A functional polymorphism of the catechol-O-methyltransferase (COMT) gene (Val158Met) partially appears to influence cognitive performance in schizophrenia subjects and healthy controls by modulating prefrontal dopaminergic activity. This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation (CRT). Method 145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling. Subjects were evaluated on neurocognitive assessments (MATRICS) and clinical symptoms (PANSS) at baseline and endpoint after 12 weeks of CRT. "Improvement" was defined as ≥ 67% of cognitive domains (≥ 4) showing performance increases. If ≤ 67% (≤ 2) of domains improved, the change was defined as "minimal improvement." A general linear model was conducted for change of each cognitive domain. Results Of 145 subjects, data from 138 subjects were usable. Distribution of COMT genotype: Met/Met: 28 (20.29%), Val/Met: 61 (44.20%), and Val/Val: 49 (35.51%). No significant differences were seen among genotype groups at baseline or across genotype group for “Improvement” vs. “Minimal Improvement.” GLM analysis showed significant differences in Verbal Learning (p = 0.003), Visual Learning (p = 0.014) and Attention/Vigilance (p = 0.011) favoring Met/Met and Val/Met groups. Conclusions The low activity Met allele (Met/Met; Val/Met) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT.

Factors Associated With Response and Resistance to Cognitive Remediation in Schizophrenia: A Critical Review

“…In a controlled study on CACR intervention in schizophrenia patients, Bosia et al (2007) found how COMT polymorphism might predict cognitive gain after 3-months follow-up, with a higher improvement in the Quality of Life Scale (QLS) in Met polymorphism after CR in comparison to Val/Val polymorphism after standard treatment. In line with these findings, a more recent study showed how COMT Val/Met and Met/Met genotype was linked to CR efficacy, with a greater improvement in three MATRICS cognitive domains—verbal learning, visual learning, and attention/vigilance—compared to Val/Val genotype (Lindenmayer et al, 2015). In contrast to these positive findings other studies did not find such a great association (or no association) between COMT Met/Met genotype and greater improvement after CR (Greenwood et al, 2011; Twamley et al, 2014).…”

“…COMT gene variability has been associated with cognitive performance in schizophrenia (Diaz-Asper et al, 2008) and with CR response, although results have been equivocal (Bosia et al, 2007, 2014a; Greenwood et al, 2011; Pieramico et al, 2012; Panizzutti et al, 2013; Lindenmayer et al, 2015). In a controlled study on CACR intervention in schizophrenia patients, Bosia et al (2007) found how COMT polymorphism might predict cognitive gain after 3-months follow-up, with a higher improvement in the Quality of Life Scale (QLS) in Met polymorphism after CR in comparison to Val/Val polymorphism after standard treatment.…”

Polymorphisms in Serotonergic Pathways Influence the Outcome of Antidepressant Therapy in Psychiatric Inpatients

“…The potential of these drugs to improve executive cognitive function by selectively increasing dopamine load in the frontal cortex but not in subcortical territories, and the possibility that response to them may be modified by a COMT polymorphism, provides a novel genotype-based targeted pharmacological approach without abuse potential for the treatment of cognitive disorder in schizophrenia and in other conditions involving prefrontal cortex dysfunction." 75 COMT genotype and response to cognitive remediation in schizophrenia http://www.ncbi.nlm.nih.gov/pubmed/26255563 76 "This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation (CRT)… The low activity Met allele (Met/Met; Val/Met) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT." 76 Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine http://www.ncbi.nlm.nih.gov/pubmed/20414144 77 "The results of this study extend earlier findings with the COMT genotypes to additional measures of cognition, and suggest that the presence of the val allele is associated with poorer performance and greater improvement with a stimulant drug."…”

“…75 COMT genotype and response to cognitive remediation in schizophrenia http://www.ncbi.nlm.nih.gov/pubmed/26255563 76 "This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation (CRT)… The low activity Met allele (Met/Met; Val/Met) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning, Visual Learning and Attention/Vigilance after CRT." 76 Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine http://www.ncbi.nlm.nih.gov/pubmed/20414144 77 "The results of this study extend earlier findings with the COMT genotypes to additional measures of cognition, and suggest that the presence of the val allele is associated with poorer performance and greater improvement with a stimulant drug." 77 Tolcapone improves cognition and cortical information processing in normal human subjects http://www.ncbi.nlm.nih.gov/pubmed/17063156 78 "We found significant drug effects on measures of executive function and verbal episodic memory, individuals with val/val genotypes improved, whereas individuals with met/met genotypes worsened on tolcapone."…”

Overlapping protein-coding genes in human genome and their coincidental expression in tissues

“…For example, if the expression levels of overlapping genes are inversely related, this would cause gene function deletion or mutation 13,33,34 . Several studies have revealed that the functional impairment of overlapping genes may be related to diseases or associated with malignant tumours; for instance, CBS is related to homocystinuria 35 , TR and COMT may be associated with schizophrenia 36 and CHEK2 may be involved in osteosarcoma 33 . However, the current study examined only the structures and associations of expression levels of overlapping genes, which limits the understanding of overlapping gene outcomes in humans.…”