COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

Abstract

Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val158Met polymorphism influences outcome on a cognitive battery 6 months following mTBI—Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1–5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13–15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met158/Met158 29 %, Met158/Val158 47 %, Val158/Val158 24 %) show that the COMT Met158 allele (mean 101.6±SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val158/Val158 homozygotes (93.8±SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p=0.017). The COMT Val158Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val158Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.

Facial emotion recognition in schizophrenia: An exploratory study on the role of comorbid alcohol and substance use disorders and COMT Val158Met

“…Phasic dopamine is likely to be involved in FER through mesolimbic projections toward the amygdala. In addition, although from different clinical populations, COMT Val158Met polymorphism is associated with nonverbal cognition (Winkler et al, ).…”

COMT and ANKK1 Genetics Interact With Depression to Influence Behavior Following Severe TBI

“…Thus, the A2 allele, may actually impart a greater risk for poor DA modulation that differs from healthy populations. While other genetic components of the DA system may influence outcomes, COMT and ANKK1 are currently the only genes with both a strong mechanistic rationale and previously documented associations with other TBI outcomes (cognition) in the literature 47,48,49 .…”

Cognitive, Experiential and Genetic Contribution to Depressive Symptoms in Male and Female Students with a History of Concussion

“…Catechol-o-methyltransferase (COMT) is the main regulator of dopaminergic synaptic transmission as it is an enzyme responsible for degrading dopamine (DA) (Axelrod and Tomchick, 1958;Winkler et al, 2015). Dopaminergic synaptic transmission is important for regulating cognition as low levels of DA within the PFC have been associated with deficits in executive function (Logue and Gould, 2014).…”

“…investigate the presence of the COMT Val 158 Met polymorphism and cognitive symptoms 6 months after injury. Using various measures of cognitive function, their results revealed that individuals with a COMT Met 158 allele had a significantly higher processing speed and the difference was associated with concussion injury severity (Winkler et al, 2015).…”

“…These findings are contrary to those by Winkler and colleagues (2015), who found the Met allele to be associated with better executive performance compared to the Val allele 6 months after concussive injury. However, Winkler et al (2015) did not include a non-injured control group, and therefore it is possible that the differences in executive function would have existed regardless of concussive injury.…”