First Demonstration of Double Dissociation between COMT-Met158 and COMT-Val158 Cognitive Performance When Stressed and When Calmer

Abstract

We present here the first evidence of the much-predicted double dissociation between the effect of stress on cognitive skills [executive functions (EFs)] dependent on prefrontal cortex (PFC) by catechol-O-methyltransferase (COMT) genotype. The COMT gene polymorphism with methionine (Met) at codon 158 results in more dopamine (DA) in PFC and generally better EFs, while with valine (Val) at codon 158 the result is less PFC DA and generally poorer EFs. Many have predicted that mild stress, by raising PFC DA levels should aid EFs of COMT-Vals (bringing their PFC DA levels up, closer to optimal) and impair EFs of COMT-Mets (raising their PFC DA levels past optimal). We tested 140 men and women in a within-subject crossover design using extremely mild social evaluative stress. On trials requiring EFs (incongruent trials) of the Flanker/Reverse Flanker task, COMT-Val158 homozygotes performed better when mildly stressed than when calmer, while COMT-Met158 carriers performed worse when mildly stressed. Two other teams previously tried to obtain this, but only found stress impairing EFs of COMT-Mets, not improving EFs of COMT-Vals. Perhaps we found both because we used a much milder stressor. Evidently, the bandwidth for stress having a facilitative effect on EFs is exceedingly narrow.

Dopamine, Cognitive Flexibility and IQ: Epistatic COMT:DRD2 Gene-Gene Interactions Modulate Mental Rigidity

“…Dopamine dysfunction in the PFC and striatum has been shown to shape schizophrenia in particular (Durstewitz & Seamans, 2008;Simpson, Kellendonk, & Kandel, 2010). Defining the dopaminergic basis of inflexible behavior is therefore critical for advancing psychopharmacological research and for understanding paradoxical or personalized treatment effects (Cools, 2019;Durstewitz & Seamans, 2008) as well as the effects of stress (Diamond, 2011;Zareyan et al, 2021). The implications of our observations are that the cognitive enhancing effects of dopaminergic agonists will be most prominent in individuals with low IQ, or presumably also, low working memory capacity.…”

Learning of uncertainty in an introductory astronomy course in remote asynchronous delivery during Covid-19 lockdown

“…The learning of "how to describe or assess uncertainty" would be of universal concern for all students. A recent dopamine study showed that most people could not use the "very mild stress" as stimulation to increase their executive function capability, in contrary to the common expectation that a small amount of stress for the raising of dopamine could facilitate the executive function in the cognition process (Zareyan, et al, 2020). Familiarity with the uncertainty in introductory astronomy would be transferred to a deeper understanding of uncertainty in general and could reduce daily life stress due to uncertainty.…”

NMDAR Neurotransmission Needed for Persistent Neuronal Firing: Potential Roles in Mental Disorders

“…In contrast to the dlPFC, high levels of catecholamines and glucocorticoids enhance the affective functioning of the amygdala (81)(82)(83), thus flipping the brain from a reflective to reflexive state. The rapid loss of dlPFC executive and working memory functions from a hypercatecholaminergic state has now been documented in humans (84)(85)(86) in addition to the original studies in rodents and monkeys (9,77,78). Thus, BA25 and amygdala can rapidly remove their regulation from higher order PFC circuits through activation of excessive catecholamine release in these higher PFC regions (Figure 4B).…”