Nora T. Walter

Investigating the genetic basis of altruism: the role of the COMT Val158Met polymorphism

Findings from twin studies yield heritability estimates of 0.50 for prosocial behaviours like empathy, cooperativeness and altruism. First molecular genetic studies underline the influence of polymorphisms located on genes coding for the receptors of the neuropeptides, oxytocin and vasopressin. However, the proportion of variance explained by these gene loci is rather low indicating that additional genetic variants must be involved. Pharmacological studies show that the dopaminergic system interacts with oxytocin and vasopressin. The present experimental study tests a dopaminergic candidate polymorphism for altruistic behaviour, the functional COMT Val158Met SNP. N = 101 healthy Caucasian subjects participated in the study. Altruism was assessed by the amount of money donated to a poor child in a developing country, after having earned money by participating in two straining computer experiments. Construct validity of the experimental data was given: the highest correlation between the amount of donations and personality was observed for cooperativeness (r = 0.32, P ≤ 0.001). Carriers of at least one Val allele donated about twice as much money as compared with those participants without a Val allele (P = 0.01). Cooperativeness and the Val allele of COMT additively explained 14.6% of the variance in donation behaviour. Results indicate that the Val allele representing strong catabolism of dopamine is related to altruism.

Internet Addiction and Personality in First-Person-Shooter Video Gamers

The present study investigated the influence on Internet addiction of numerous variables ranging from personality to psychological and physical well-being, in a large and highly ecologically valid ...

Ignorance Is No Excuse: Moral Judgments Are Influenced by a Genetic Variation on the Oxytocin Receptor Gene.

Perspective-taking has become a main focus of studies on moral judgments. Recent fMRI studies have demonstrated that individual differences in brain activation predict moral decision making. In particular, pharmacological studies highlighted the crucial role for the neuropeptide oxytocin in social behavior and emotional perception. In the present study N=154 participants were genotyped for a functional polymorphism (rs2268498) in the promoter region of the OXTR gene. We found a significant difference between carriers and non-carriers of the C-allele in exculpating agents for accidental harms (F((1,152))=11.49, p=.001, η(2)=.07) indicating that carriers of the C-allele rated accidentally committed harm as significantly more blameworthy than non-carriers. This is the first study providing evidence for a genetic contribution to moral judgments.

Interaction effect of functional variants of the BDNF and DRD2/ANKK1 gene is associated with alexithymia in healthy human subjects.

Objective: To test the hypothesis that the interaction between the brain-derived neurotrophic factor (BDNF) and dopamine receptor D2 (DRD2)/ANKK1 gene contributes to individual differences in alexithymia. The personality construct of alexithymia refers to difficulties in emotional self-regulation and contributes as a risk factor to several mental disorders. Alexithymic individuals show an impoverished conscious experience of emotions but an intact autonomic emotional response. Persons with high alexithymia scores reportedly show a reduced activation of the anterior cingulate cortex (ACC) during the processing of emotional stimuli. An interaction between two polymorphisms on the BDNF and DRD2/ANKK1 gene has been recently associated with reduced gray matter volume in the ACC and higher trait anxiety. Methods: We conducted a genetic association study. A total of 664 healthy participants completed the Toronto Alexithymia Scale questionnaire and were genotyped for the BDNF Val66Met (rs6265) and the DRD2/ANKK1 Taq IA (rs1800497) polymorphisms. Results: Carriers of at least one BDNF 66Met and one DRD2/ANKK1 A1 allele showed the highest scores in the total Toronto Alexithymia Scale and in the subscale “Difficulties Identifying Feelings.” Conclusion: In line with recent studies investigating the role of BDNF Val66Met and DRD2/ANKK1 Taq IA polymorphisms on anxiety and gray matter volume in the ACC, our findings provide the first evidence for a genetic contribution to alexithymia. ACC = anterior cingulate cortex; TAS-20 = Toronto Alexithymia Scale; DIF = TAS-20 subscale Difficulties Identifying Feelings; DDF = TAS-20 subscale Difficulties Describing Feelings; EOT = TAS-20 subscale Externally Oriented Thinking; BDNF = brain-derived neurotrophic factor; DRD2 = dopamine receptor D2; CBF = cerebral blood flow; TCI = Temperament and Character Inventory; VTA = ventral tegmental area; PD = panic disorder.

Genetically determined dopamine availability predicts disposition for depression

Although prominent personality theories postulate orthogonality between traits of positive emotionality (PEM) and negative emotionality (NEM), empirical evidence often demonstrates the opposite indicating a negative relationship. Therefore, it is not surprising that dopaminergic (DA) gene loci have been related to traits of positive and of NEM. The present genetic association study investigates the influence of two functional DA gene polymorphisms on Sadness as defined by the Affective Neuroscience Personality Scales (ANPS) in healthy Caucasians (n= 1041). We observed a significant interaction effect between the 10‐repeat (10R) allele of the dopamine transporter (DAT1) gene and the methionine (Met) allele of the catechol‐O‐methyltransferase (COMT) Val158Met polymorphism (F(1,1018)= 11.11; P < 0.001). Carriers of the 9R/9R and the Val/Val genotype showed dramatically reduced Sadness scores in comparison to the other three genotype configurations. Both the 9R/9R and the Val/Val genotypes characterized by reduced transporter density and high dopamine catabolism, respectively, have been separately related to personality traits of PEM and externalizing behavior in the past. The present findings indicate that gene variations of the DA system previously associated with PEM are at the same time protective against high NEM and can therefore constitute a resilience factor against depression.

On the molecular genetics of flexibility: The case of task-switching, inhibitory control and genetic variants

The adjustment of behavior to changing goals and environmental constraints requires the flexible switching between different task sets. Cognitive flexibility is an endophenotype of executive functioning and is highly heritable, as indicated by twin studies. Individual differences in global flexibility as assessed by reaction-time measurement in a task-switching paradigm were recently related to a single nucleotide polymorphism in the vicinity of the dopamine d2 receptor gene DRD2. In the present study, we assessed whether the DRD2 gene is related to backward inhibition, a control mechanism that contributes to cognitive flexibility by reducing proactive interference by no longer relevant task sets. We found that carriers of the DRD2 A1+ variant who have a lower striatal dopamine d2 receptor density than A1– carriers show a larger backward inhibition effect. This is in line with previous results demonstrating increased behavioral flexibility in carriers of this genetic variant. The discussion relates the present finding to those of previous studies assessing the neurogenetic foundations of inhibitory control.

Evidence for the modality independence of the genetic epistasis between the dopaminergic and cholinergic system on working memory capacity

Working memory (WM) is fractionated into systems for visuospatial and phonological information. Recently, it has been shown that the dopamine d2 receptor gene DRD2 and CHRNA4, the gene coding for the nicotinic acetylcholine receptors alpha4 subunit, interact epistatically on visuospatial WM capacity. In the present study, we show a similar interaction on phonological WM capacity in N=137 healthy subjects genotyped for two single nucleotide polymorphisms (DRD2 rs6277 and CHRNA4 rs1044396). Given the functional independence of the two systems we hypothesize that the genetic interaction targets the central executive which is the common control process for both systems.

A genetic contribution to cooperation: Dopamine-relevant genes are associated with social facilitation

Social loafing and social facilitation are stable behavioral effects that describe increased or decreased motivation, as well as effort and cooperation in teamwork as opposed to individual working situations. Recent twin studies demonstrate the heritability of cooperative behavior. Brain imaging studies have shown that reciprocity, cooperativeness, and social rewards activate reward processing areas with strong dopaminergic input, such as the ventral striatum. Thus, candidate genes for social behavior are hypothesized to affect dopaminergic neurotransmission. In the present study, we investigated the dopaminergic genetic contribution to social cooperation, especially to social loafing and social facilitation. N = 106 healthy, Caucasian subjects participated in the study and were genotyped for three polymorphisms relevant to the dopaminergic system (COMTval158met, DRD2 c957t, DRD2 rs#2283265). In addition to a main effect indicating an increased performance in teamwork situations, we found a significant interaction between a haplotype block covering both DRD2 single nucleotide polymorphisms (SNPs) (rs#6277 and rs#2283265), henceforth referred to as the DRD2-haplotype block, and the COMT val158met polymorphism (rs#4680) with social facilitation. Carriers of the DRD2 CT-haplotype block and at least one Val-allele showed a greater increase in performance in teamwork settings when compared with carriers of the CT-haplotype block and the Met/Met-genotype. Our results suggest that epistasis between COMTval158met and the two DRD2 SNPs contributes to individual differences in cooperativeness in teamwork settings.

The DRD2 C957T polymorphism and the attentional blink--a genetic association study.

The attentional blink phenomenon (AB) describes a transient deficit in temporally selective visual attention regarding the processing of the second of two target stimuli in a rapid serial visual presentation (RSVP) task. The AB is a very prominent paradigm in the Cognitive Neurosciences that has been extensively studied by diverse psychophysiological techniques such as EEG or fMRI. Association studies from molecular genetics are scarce although the high heritability of higher cognitive functioning is proven. Only one seminal study reported an association between AB magnitude and the dopamine receptor D2 (DRD2) C957T polymorphism (Colzato et al., 2011). This functional polymorphism influences striatal D2 receptor binding affinity and thereby the efficacy of dopaminergic neurotransmission which is important for working memory and attentional processes. Colzato et al. (2011) reported that DRD2 C957T T/T-carriers exhibit a significant smaller AB than C-allele carriers. In the present study this influence of the DRD2 SNP on the AB could not be replicated in N=211 healthy participants. However, a significantly larger lag 1 sparing was observed for homozygous T/T-carriers. Moreover, carriers of at least one T-allele showed a significantly poorer performance in the identification of T1. In general, these results support the notion of a role of the dopaminergic system on the AB. However, as our results do not parallel previous findings the exact nature of this influence and its dependence on task parameters will have to be examined in further genetic association studies.