Genetic and epigenetic serotonergic markers predict the ability to recognize mental states

Reuter, Martin; Felten, Andrea; Zamoscik, Vera; Bravo, Rafael; Ugartemendia, Lierni; Koehler, Peter; Rodríguez, Ana B.; Plieger, Thomas

doi:10.1016/j.physbeh.2020.113143

Cited by 4 publications

(9 citation statements)

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“…An ADHD-specific relation between DNA methylation and reaction time variability in a motivational Go/NogoTask has been reported before [ 13 ], supporting the influence of DNA methylation on both, variability and impulsivity. DNA methylation has been linked to personality traits/endophenotypes such as aggression [ 60 ], and the ability to recognize mental states [ 38 ] as well as in the context of affective disorders [ 12 , 61 ] to rs-fMRI-related PFC activity [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

“…the WI phenotype is a direct result of the cumulative effect of WI phenotype (ADHD>TDC) and genetically moderated TPH2 variation (T + >GG). Finally, the effect of DNA methylation on WI was examined as suggested by Reuter et al (2020) [ 38 ] using multiple regressions taking TPH2 genotype as well as age and sex into account. We predicted a positive relation between DNA methylation and wVar in terms of the higher methylation, the higher wVar.…”

Section: Introductionmentioning

confidence: 99%

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Serotonergic modulation of normal and abnormal brain dynamics: The genetic influence of the TPH2 G-703T genotype and DNA methylation on wavelet variance in children and adolescents with and without ADHD

Akhrif¹,

Romanos²,

Peters³

et al. 2023

PLoS ONE

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. Core symptoms of ADHD, such as impulsivity, are caused by an interaction of genetic and environmental factors. Epigenetic modifications of DNA, such as DNA methylation, are thought to mediate the interplay of these factors. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to ADHD, e.g., showing that TPH2 G-703T (rs4570625) polymorphism influences response control and prefrontal signaling in ADHD patients. In this (epi)genetic imaging study we examined 144 children and adolescents (74 patients, 14 females) using fMRI at rest and during performing a waiting impulsivity (WI) paradigm. Both, TPH2 G-703T (rs4570625) genotype and DNA methylation in the 5’ untranslated region (5’UTR) of TPH2 were associated with wavelet variance in fronto-parietal regions and behavioral performance, taking TPH2 genotype into account. In detail, comparisons between genotypes of patients and controls revealed highest wavelet variance and longest reaction times in patients carrying the T allele [indicative for a gene-dosage effect, i.e., the WI phenotype is a direct result of the cumulative effect of ADHD and TPH2 variation]. Regressions revealed a significant effect on one specific DNA methylation site in ADHD patients but not controls, in terms of a significant prediction of wavelet variance in fronto-parietal regions as well as premature responses. By the example of the TPH2 G-703T (rs4570625) polymorphism, we provide insight into how interactive genetic and DNA methylation affect the ADHD and/or impulsive endophenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serotonergic modulation of normal and abnormal brain dynamics: The genetic influence of the TPH2 G-703T genotype and DNA methylation on wavelet variance in children and adolescents with and without ADHD

Akhrif¹,

Romanos²,

Peters³

et al. 2023

PLoS ONE

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“…The dopamine D4 receptor gene ( DRD4 ) [ 69 , 70 , 71 , 72 , 73 ]; the dopamine reuptake transporter polymorphisms in the 3′ UTR ( DAT1 ) [ 70 , 72 , 73 ]; Zinc-finger protein gene polymorphism rs1344706 ( ZNF804A ) [ 74 , 75 ]; the catechol-O-methyltransferase enzyme gene polymorphism Val158Met ( COMT ) [ 70 , 71 , 73 , 76 ]; the serotonin carrier gene polymorphism 5-HTTLPR ( SCL6A4 ) [ 73 , 77 ]; the oxytocin receptor gene polymorphisms ( OXTR ) and the oxytocin gene polymorphisms ( OXT ) [ 71 , 78 , 79 , 80 , 81 , 82 , 83 ]; the arginine vasopressin hormonal genes polymorphisms ( AVP ) and the arginine vasopressin subtype 1A receptor gene polymorphisms ( AVPR1A ) [ 79 , 84 ]; other polymorphisms including the ones belonging to MAO-A genes, EFHC2 genes, and GTF2I genes [ 85 , 86 , 87 ].…”

Section: Resultsmentioning

confidence: 99%

“…The selected studies are summarized in Table 1 . Of these 19 studies, eight recruited a sample of children [ 69 , 70 , 71 , 78 , 79 , 80 , 84 , 87 ], ten a sample of adults [ 72 , 73 , 74 , 75 , 76 , 77 , 81 , 83 , 85 , 86 ], and one a sample of adults and teenagers [ 82 ].…”

Section: Resultsmentioning

confidence: 99%

Theory of Mind: A Brief Review of Candidate Genes

Silvestri,

Scaini,

Giani

et al. 2024

Genes

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Deficits in theory of mind (ToM), known as the ability to understand the other’s mind, have been associated with several psychopathological outcomes. The present systematic review aims to summarize the results of genetic studies that investigated gene polymorphisms associated with mentalization performance tasks in children and adults. The systematic review was carried out following PRISMA guidelines, and the literature search was conducted in PubMed and EBSCOhost using the following keywords: ‘theory of mind, mentalizing, mindreading’ and ‘gene, genetic basis’. Nineteen studies met the eligibility criteria for inclusion. Most of the literature focused on the role of DRD4, DAT1, OXTR, OXT, COMT, ZNF804A, AVP, AVPR, SCL6A4, EFHC2, MAO-A, and the family of GTF2I genes in influencing ToM. However, controversial results emerged in sustaining the link between specific genetic polymorphisms and mentalization abilities in children and adults. Available data show heterogeneous outcomes, with studies reporting an association between the same family genes in subjects of the same age and other studies reporting no correlation. This does not allow us to draw any solid conclusions but paves the way for exploring genes involved in ToM tasks.

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“…Also, the monoamine oxidase (MAO) is another important enzyme involved in the PFC circuitry, being responsible for the deamination of monoamine neurotransmitters. Notably, MAO-A is involved in the catabolism of serotonin; a recent study on its polymorphism MAOA-uVNTR showed that a high activity allele is related to lower 5-HT levels, leading to worse performance in social cognition [41]. Accordingly, this polymorphism has been reported in relation to enhanced aggressive behaviors in animals and humans, cause by increased amygdala reactivity and decreased prefrontal activity during emotional arousal [42,43].…”

Section: Snps and Neurocognitionmentioning

confidence: 99%

The Impact of Genetics on Cognition: Insights into Cognitive Disorders and Single Nucleotide Polymorphisms

Spoto,

Di Rosa,

Nicotera

2024

JPM

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This article explores the complex relationship between genetics and cognition, specifically examining the impact of genetic variants, particularly single nucleotide polymorphisms (SNPs), on cognitive functions and the development of neuropsychiatric disorders. Focusing on neurotransmitter regulation within the prefrontal cortex’s dopaminergic circuits, this study emphasizes the role of genes like COMT, PRODH, and DRD in shaping executive functions and influencing conditions such as ADHD and schizophrenia. Additionally, it explores the significance of genetic factors in neurodevelopmental disorders, emphasizing the need for early identification to guide appropriate therapeutic interventions. This article also investigates polymorphisms in the transsulfuration pathway, revealing their association with cognitive impairment diseases. Computational analyses, including machine learning algorithms, are highlighted for their potential in predicting symptom severity in ADHD based on genetic variations. In conclusion, this article underscores the intricate interplay of genetic and environmental factors in shaping cognitive outcomes, providing valuable insights for tailored treatments and a more comprehensive understanding of neuropsychiatric conditions.

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Genetic and epigenetic serotonergic markers predict the ability to recognize mental states

Cited by 4 publications

References 37 publications

Serotonergic modulation of normal and abnormal brain dynamics: The genetic influence of the TPH2 G-703T genotype and DNA methylation on wavelet variance in children and adolescents with and without ADHD

Serotonergic modulation of normal and abnormal brain dynamics: The genetic influence of the TPH2 G-703T genotype and DNA methylation on wavelet variance in children and adolescents with and without ADHD

Theory of Mind: A Brief Review of Candidate Genes

The Impact of Genetics on Cognition: Insights into Cognitive Disorders and Single Nucleotide Polymorphisms

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