Abstract
BackgroundDopamine in prefrontal cortex (PFC) modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT) Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required.MethodsUsing a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67) and healthy controls (n = 186) genotyped for the Val/Met variation.ResultsIn both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated.ConclusionsOur results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.
Highlights
Dopamine in prefrontal cortex (PFC) modulates core cognitive processes, notably working memory and executive control
A COMT polymorphism, Val158Met, plays a central role in cortical dopamine degradation, with the Val allele associated with greater COMT enzyme activity, greater dopamine degradation and less synaptic dopamine than the Met allele [3,4]
First, given the large element of automaticity in reading, and the simple but rapid mapping required between lexical-semantic aspects of the stimuli and response, we predicted the Met allele would be associated with superior performance when the demand for cognitive flexibility and/or control was low, namely simple reading of the words “green” and “red”
Summary
Dopamine in prefrontal cortex (PFC) modulates core cognitive processes, notably working memory and executive control. Understanding genes that regulate dopamine in PFC - such as catechol-Omethyltransferase (COMT) gene on chromosome 22q11 - may help to unravel the complex neurobiological processes that underlie cognitive function and dysfunction in health and illness. Considerable evidence suggests that Met alleles are associated with more efficient patterns of prefrontal cortical activation and superior cognitive performance. This pattern has been observed in schizophrenia patients [5], and in most of the literature, COMT effects are independent of psychiatric diagnosis or risk status, suggesting that genotype modulates typical as well as impaired prefrontal cognition [5]. Given the complexity of clinical diagnosis, cognitive performance has been proposed as an intermediate phenotype for investigation of schizophrenia [11]
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