Browsing by Subject "Taq1A"
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(2022)The aim of the study. Spontaneous eye blink rate (sEBR) is a behavioral index that has been linked to frontostriatal dopaminergic activity. Reduced or increased dopaminergic activity due to clinical conditions tends to be associated with lower or higher sEBR, respectively, and sEBR can be modulated by pharmacological agents that affect dopamine signaling. Consequently, sEBR could serve as an easily accessible method of assessing brain dopaminergic tone indirectly in humans. It might be preferable to more expensive and invasive techniques such as positron emission tomography. However, it remains unclear whether variations in dopaminergic genes predict sEBR. In this cross-sectional study, the relationship between sEBR and dopaminergic genotype was examined in two samples. Two genetic polymorphisms were focused on: the COMT Val158Met polymorphism and the A1 allele of the Taq1A polymorphism. It was hypothesized that the COMT Val158Met polymorphism is associated with higher sEBR, and that the A1 allele of the Taq1A polymorphism is associated with lower sEBR. As BMI and diet have been linked with altered striatal dopamine function, the possible association between BMI, diet, and sEBR was studied exploratively. Methods. Data from three cross-sectional studies was used in this study: The intervention study (n = 31) is an experimental study that examines the effect of acute phenylalanine/tyrosine depletion on cognitive measures. The GREADT study (n = 86) focuses on the effects of genotype and diet on dopamine tone. The BEDOB study (n = 69) investigates neurocognitive mechanisms in obesity and binge eating disorder. Similar methodologies were used in the GREADT and the BEDOB studies, which is why these datasets were combined for the analyses. Blink rates were measured using an infrared eye tracking system. The participants completed the Dietary Fat and free Sugar Questionnaire (DFS) to assess how much they consumed saturated fat and refined sugar. In the GREADT/BEDOB sample, the associations between the polymorphisms, BMI, DFS-score, and sEBR were examined with univariate analyses of variance. In the intervention study sample, a generalized linear mixed model was run to check whether sEBR changed in the intervention and whether the genotypes, BMI, or DFS-score affected sEBR. Results. No influence of the genotypes was found on sEBR in either of the samples. BMI had a significant effect on sEBR in the GREADT/BEDOB sample. The association was significant in the overweight/obese group but not in the normal weight group. DFS-score did not influence sEBR in either of the samples. Conclusions. The results of this study converge with those of authors suggesting caution in using sEBR as a proxy for central dopamine functioning of healthy humans. In future studies, particular attention should be paid to methodological considerations when studying sEBR.
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(2022)The aim of the study. Working memory (WM) is a cognitive function that relies on the neurotransmitter dopamine. WM has multiple subfunctions: maintaining relevant information, ignoring distractors, and updating the information when needed. Information maintenance and ignoring irrelevant stimuli are associated with brain activity in the prefrontal cortex and updating information with the striatum. A connection between polymorphisms within the dopaminergic genes COMT (COMT Val158Met polymorphism) and DRD2/ANKK1 (Taq1A polymorphism), and WM performance has been established in previous studies, and these genes seem to impact dopamine signaling in the prefrontal cortex and striatum, respectively. The present study investigates associations between dopaminergic gene polymorphisms and WM performance. The main research questions include the main effects and interactions that the genes have to WM on performance overall and WM stability and flexibility in particular. The study investigates also whether obesity, diet, and age affect WM performance, as there are indications for these from previous studies. Methods. Data from three separate cross-sectional studies with a total of 244 participants was used. A computer-based visual working memory task was used to assess the WM performance measures accuracy and reaction time. Other measurements included blood measures, Body Mass Index (BMI), and the Dietary Fat and free Sugar Questionnaire (DFS). Results and conclusion. In WM accuracy analyses, there was a significant main effect for the task condition as well as interactions between the COMT*task condition and COMT*Taq1A*task condition. In the three-way interaction analysis for WM accuracy, the most beneficial combination was Met/Met & A1- in the task condition measuring the stability, and Val/Met & A1+ in the task condition measuring the flexibility. This result gives support for established knowledge about how Met/Met combined with A1- is beneficial especially for WM stability and maintenance. Also, the inverted-U shape theory and previous studies' results of A1+ being beneficial in executive functions updating tasks, give support to the result regarding WM flexibility. In the three-way interaction reaction time analysis, the combination of Val/Met & A1+ was the fastest in every task condition. However, the significant differences were mainly between A1- and A1+ genotypes when combined with Val/Met and between Met/Met and Val/Met genotypes when combined with A1-. The two-way interaction between COMT Val158Met and task condition did not remain significant in pairwise comparisons. In reaction time analyses, COMT Val158Met and Taq1A had a significant main effect where reaction times followed the order: Met/Met < Val/Val < Val/Met, with Val/Met being significantly slower than the others and in Taq1A A1+ < A1-, with a significant difference. Adding age, BMI, and DFS to the analyses did not affect the significant/non- significant main effects or interactions in the analyses. The results of this thesis converge with the previous knowledge about these genotypes having an interacting effect on working memory stability and flexibility. However, these effects are complex to interpret as the results and their directions differed between the task conditions and outcome measurements. In the main outcome variable (accuracy), the result regarding the WM stability is well in line with previous literature about the Met/Met & A1- combination being beneficial to WM performance, and the result about Val/Met & A1+ being beneficial for WM flexibility gets preliminary support from executive function studies, but also opens new research avenues regarding the WM flexibility subfunction.
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(2022)Objectives. Motivational contexts exert a profound influence on behavior biasing actions in sometimes detrimental ways. In Pavlovian bias, reward-predicting conditioned cues elicit approach behavior while aversively associated cues elicit withdrawal, with capacity to impact instrumental goal-driven behavior. Similar bias has been suggested to be produced by instrumental learning. Motivational biases have been linked to dopaminergic system but the precise role of dopamine in their modulation is unclear. The present study investigated genetically driven variation in Pavlovian and instrumental learning biases by comparing task performance in subjects carrying different variants of two dopaminergic SNPs, COMT Val108/158Met and DRD2/ANKK1Taq1A. Associations with BMI, diet, age and gender were studied. All subjects were expected to show motivational bias while no direct hypotheses were made concerning genotypic or lifestyle-mediated effects due to exploratory nature of the study. Methods. 160 subjects completed a probabilistic Go/NoGo learning task in an experimental within-subject design. Generalized mixed-model logistic regressions were used to predict differences by genotype in Go responding with and without covariants. Differences by genotype in computationally modelled latent bias estimates were studied with linear regression. Results and Conclusions. Confirming expectations, an overall effect of motivational bias and a general bias towards active responding were found. Relative to Val/Met and A1+, carriers of COMT Val/Val and Taq1A A1- variants showed superior learning of correct Go responses, indicating enhanced instrumental bias. BMI was inversely associated with learning rate while diet, age and gender did not explain variance. Results partly contradict previous findings and highlight the mixed nature of research regarding associations between dopaminergic SNPs and motivational biases.
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