Catechol-O-methyltransferase Val158Met genotype affects neural correlates of aversive stimuli processing

Würflein, Heidi; Schreppel, Theresa; Koehler, Saskia; Mühlberger, Andreas; Reif, Andreas; Canli, Turhan; Romanos, Marcel; Jacob, Christian; Lesch, Klaus‐Peter; Fallgatter, Andreas J.

doi:10.3758/cabn.9.2.168

Cited by 32 publications

(27 citation statements)

References 23 publications

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“…9 COMT is also expressed in the amygdala, 10 an area of the brain important for socio-emotional functioning. It has been proposed that elevated dopamine in these areas enhances the salience of the environmental threat.…”

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confidence: 99%

“…8 It is considered to be a good candidate for studying the genetic basis of stress sensitivity because it encodes an enzyme that is involved in the breakdown of dopamine in the prefrontal cortex. 9 COMT is also expressed in the amygdala, 10 an area of the brain important for socio-emotional functioning. It has been proposed that elevated dopamine in these areas enhances the salience of the environmental threat.…”

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confidence: 99%

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The catechol‐O‐methyltransferase (COMT) Val158Met polymorphism moderates the effect of antenatal stress on childhood behavioural problems: longitudinal evidence across multiple ages

Thompson¹,

Sonuga‐Barke²,

Morgan³

et al. 2011

Develop Med Child Neuro

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SDQ Strengths and DifficultiesQuestionnaire SGA Small for gestational age AIM The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene was analysed to determine its association with maternal stress and childhood total difficulties.METHOD Data were collected at birth from a group of infants who were born small for gestational age and a group who were born at an appropriate size for gestational age and had been enrolled in the Auckland Birthweight Collaborative Study. Children were followed up at the ages of 1 year, 3 years 6 months, 7 years, and 11 years. At the age of 11 years, DNA samples were collected from 546 children (270 females, 276 males): 227 children born small for gestational age and 319 children born at an appropriate size for gestational age. The main independent variable was perceived maternal stress at birth and at 7 and 11 years of age, assessed using the total difficulties scale of the Strength and Difficulties Questionnaire. IQ was assessed at the age of 7 years.RESULTS Met ⁄ Met homozygotes were at a significantly increased risk of behavioural and emotional problems at the ages of 7 (p=0.002) and 11 years (p=0.003), relative to either heterozygous or homozygous carriers of the Val158Met polymorphism, but only when they were exposed to maternal stress in utero. Met ⁄ Met homozygotes had, on average, IQ scores that were four points higher than those of Val ⁄ Val homozygotes (p=0.010).INTERPRETATION These findings emphasize the potential long-term consequences of prenatal stress for genetically susceptible individuals during neurodevelopment in utero. Our findings add to the general understanding of the aetiology and developmental nature of childhood emotional and behavioural problems.Exposure to maternal antenatal stress can have deleterious effects on the subsequent development of offspring. A number of recent studies have reported an increased risk of socioemotional and behavioural disturbances, 1,2 including attention-deficit-hyperactivity disorder (ADHD). 3 Exposure to stress during pregnancy can influence prenatal development and increase the risk of problems in childhood. Stress-induced activation of the sympathetic nervous system causes an increase in uterine artery resistance, reducing blood flow to the fetus and potentially altering brain structure and function. 4 Moreover, cortisol secreted by the mother in response to stress can reach the fetus, 5 which in turn can influence the functioning of the fetus's hypothalamo-pituitaryadrenal axis.6 Changes in the hypothalamo-pituitary-adrenal axis can increase the risk of later behavioural and emotional problems through an alteration of gene expression in developing brain cells. 7The catechol-O-methyltransferase (COMT) gene has received attention recently with regard to the role it plays in stress vulnerability. 8 It is considered to be a good candidate for studying the genetic basis of stress sensitivity because it encodes an enzyme that is involved in the breakdown of dopamine in the prefrontal cortex.9 COMT is ...

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confidence: 99%

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confidence: 99%

The catechol‐O‐methyltransferase (COMT) Val158Met polymorphism moderates the effect of antenatal stress on childhood behavioural problems: longitudinal evidence across multiple ages

Thompson¹,

Sonuga‐Barke²,

Morgan³

et al. 2011

Develop Med Child Neuro

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“…Specifically, the Met/Met carriers, as compared to the Val/Val carriers, are more sensitive to the unpleasant stimuli [26]. Therefore, given the regulation of COMT on dopamine activity and the link between COMT activity and Val158Met variation, we predict that Val158Met is associated with attentional bias for negative expressions and the individuals with Met allele display more attentional bias for negative emotional expressions.…”

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confidence: 91%

Genetic Variations in COMT and DRD2 Modulate Attentional Bias for Affective Facial Expressions

et al. 2013

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Studies have revealed that catechol-O-methyltransferase (COMT) and dopaminegic receptor2 (DRD2) modulate human attention bias for palatable food or tobacco. However, the existing evidence about the modulations of COMT and DRD2 on attentional bias for facial expressions was still limited. In the study, 650 college students were genotyped with regard to COMT Val158Met and DRD2 TaqI A polymorphisms, and the attentional bias for facial expressions was assessed using the spatial cueing task. The results indicated that COMT Val158Met underpinned the individual difference in attentional bias for negative emotional expressions (P = 0.03) and the Met carriers showed more engagement bias for negative expressions than the Val/Val homozygote. On the contrary, DRD2 TaqIA underpinned the individual difference in attentional bias for positive expressions (P = 0.003) and individuals with TT genotype showed much more engagement bias for positive expressions than the individuals with CC genotype. Moreover, the two genes exerted significant interactions on the engagements for negative and positive expressions (P = 0.046, P = 0.005). These findings suggest that the individual differences in the attentional bias for emotional expressions are partially underpinned by the genetic polymorphisms in COMT and DRD2.

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“…Genotyping for COMT val 158 met was accomplished using standard polymerase chain reaction procedures from a previously published protocol (Herrmann et al, 2009). For statistical testing, carriers of the A (met) variant (met + ) were compared with carriers of the G (val) allele (met − ) by classifying individuals into val/val vs. val/met vs. met/met genotype groups.…”

Section: Genotypingmentioning

confidence: 99%

Genetic contributions to acute autonomic stress responsiveness in children

Mueller

Strahler

Armbruster

et al. 2012

International Journal of Psychophysiology

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Catechol-O-methyltransferase Val158Met genotype affects neural correlates of aversive stimuli processing

Cited by 32 publications

References 23 publications

The catechol‐O‐methyltransferase (COMT) Val158Met polymorphism moderates the effect of antenatal stress on childhood behavioural problems: longitudinal evidence across multiple ages

The catechol‐O‐methyltransferase (COMT) Val158Met polymorphism moderates the effect of antenatal stress on childhood behavioural problems: longitudinal evidence across multiple ages

Genetic Variations in COMT and DRD2 Modulate Attentional Bias for Affective Facial Expressions

Genetic contributions to acute autonomic stress responsiveness in children

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