On a role

https://www.geneqol-consortium.org/wp-content/uploads/sites/9/2013/07/Munafo_DRD4-and-personality_Biol-Psychiatry-2008.pdf

Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data.

Molecular genetic studies of personality began with two high impact papers in 1996 that showed provisional associations between the dopamine DRD4 exon III repeat region and Novelty Seeking/Extraversion. These first two reports were shortly followed by an investigation linking Neuroticism/Harm Avoidance with the serotonin transporter (SLC6A4) promoter region polymorphism (5-HTTLPR). In the ensuing decade, thousands of subjects have been studied for association between these genes and personality, assessed by using self-report questionnaires, with erratic success in replication of the first findings for Novelty Seeking (DRD4) and Harm Avoidance (5-HTTLPR). Small effect sizes characteristic of non-Mendelian traits, polygenic patterns of inheritance and true heterogeneity between studies confound attempts to reach a consensus regarding the role of common polymorphisms in contributing to personality domains. Nevertheless, the current state of personality genetics is far from being bleak. Several new paradigms especially functional neuroimaging or 'imaging genomics' have strengthened the connection between 5-HTTLPR and anxiety-related personality traits. The demonstrations that early environmental information can considerably strengthen and even uncover associations between genes and behavior (Caspi's seminal studies and more recently the demonstration that early environment impacts on DRD4 and Novelty Seeking) are notable and herald a new era of personality genetics. Finally, consideration of the broader phenotypic expression of common polymorphisms (e.g. the 'social brain', altruism, etc.) and the use of new experimental paradigms including neurophysiological, neuropsychological and computer games that go beyond the narrow self-report questionnaire design will enable a deeper understanding of how common genetic polymorphisms modulate human behavior. Human personality, defined by Webster as the quality or state of being a person or the complex of characteristics that distinguishes an individual, surely requires a more encompassing view towards understanding its complex molecular genetic architecture.

The molecular genetic architecture of human personality: beyond self-report questionnaires

A meta-analysis was conducted on studies reporting data on associations between candidate genes and human personality. Studies reporting data for psychiatric populations (including organic disease and substance abuse) were excluded. A total of 46 studies contributed to the analysis. Pooled data using a fixed-effects model suggested significant associations between the 5HTT LPR, DRD4 c>t, DRD4 length, DRD2 A1/A2, DRD3 A1/A2 polymorphisms and personality traits. A multivariate analysis using a mixed-effects model and including age, sex and predominant ethnicity as covariates was applied to the analyses of 5HTT LPR and DRD4 length polymorphism data. Only the association between the 5HTT LPR polymorphism and avoidance traits remained significant (P=0.038). However, sensitivity analyses excluding data from studies reporting allele frequencies not in Hardy-Weinberg equilibrium and unpublished data resulted in this association no longer being significant. Implications for the design of future association studies of human personality are discussed, including the likely sample sizes that will be required to achieve sufficient power and the potential role of moderating variables such as sex.

Genetic polymorphisms and personality in healthy adults: a systematic review and meta-analysis.

Toward a molecular architecture of personality.

No association between dopamine D4 receptor gene exon III and –521C/T polymorphism and Novelty Seeking

No association between dopamine D4 receptor gene exon III and -521C/T polymorphism and novelty seeking.

The functional implications of the dopamine D4 receptor gene (DRD4) exon III polymorphism and its role in the modulation of temperament and in the pathophysiology of psychiatric disorders are still a matter of debate. Based on evidence from animal studies, we hypothesised that this polymorphism is involved in the modulation of the cortical response to novelty as reflected by the auditory evoked novelty P3 event-related potential. In a sample of 46 healthy volunteers, we observed an interactive effect of DRD4 exon III genotype and the eye-blink rate, a measure of central dopaminergic activity, on the novelty P3. These findings suggest that the DRD4 exon III polymorphism influences the processing of novelty and that this influence depends on tonic dopaminergic activity.

Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3

In this journal, Bachner-Melman et al.1 reported that the 48-bp variable number of tandem repeat in the third exon of the dopamine D4 receptor (DRD4 VNTR) is associated with self-reported altruism. Despite mounting evidence for a role of dopamine in prosocial behavior,2, 3, 4 this result has not been replicated yet, perhaps because of the rare usage of the applied Selflessness Scale. Here, we report a conceptual replication of the association between DRD4 VNTR and altruism measured with the well-established Revised NEO Personality Inventory (NEO-PI-R; see Strobel et al.2).

Dopamine D4 receptor gene variation impacts self-reported altruism.

Need for Cognition (NFC) is conceptualized as an individuals' tendency to engage in and enjoy effortful cognitive activity and, thus, captures one's cognitive engagement. It plays a well-established role in information processing in experimental or academic contexts. However, so far comparably little is known about its consequences for other than purely cognitive or academic outcomes. Indeed, NFC is positively associated with personality traits pertaining to Positive Emotionality (PE) and negatively to traits related to Negative Emotionality (NE). Moreover, evidence suggests NFC to be related to an active, problem-focused coping style. We therefore hypothesized NFC to mediate between life events and individual differences in PE and NE. In a sample of N = 202 volunteers from the general population, we observed that the number of past positive and negative life events had direct effects on PE, and NE, respectively, and that for positive life events, a mediating effect on PE via NFC was observed, with a higher number of past positive life events being related to higher NFC that in turn was related to increased PE. Thus, the present results lend support to the notion of NFC as an important factor supporting personal well-being by way of its mediating role between the number of past positive life events and positive affect.

/pdf/cognitive-engagement-mediates-the-relationship-between-3qhzuf054u.pdf

Cognitive Engagement Mediates the Relationship between Positive Life Events and Positive Emotionality.

Need for Cognition (NFC) and Openness to Ideas are intellectual investment traits that are characterized by a tendency to seek out, engage in and enjoy effortful cognitive activity Little, however, is known about the extent to which they are influenced by genetic and environmental factors With the present contribution, we aim at furthering our knowledge on the mechanisms underlying intellectual investment traits by following-up on a recent investigation of the role of dopaminergic gene variation in intellectual investment Employing a standard approach that relied on null-hypothesis significance testing, we found that, first, two dopaminergic genetic variants interacted in modulating individual differences in NFC, but not in Openness to Ideas; that, second, negative life events played a role in the modulation of Openness to Ideas, but not of NFC; and that, third, negative life events as assessed using another measure were only marginally related to Openness to Ideas while positive life events were associated with both Openness to Ideas and NFC, with the latter effect being also dependent on DRD4 exon III genotype However, employing a Bayesian approach, the assumption of a genetic effect on investment traits was overall not supported, while the assumption of a role of positive life events in the modulation of investment traits could be confirmed, with a tentative increment in the prediction of NFC by adding an interaction of positive life events and DRD4 variation to the main effect of positive life events Our findings underscore the importance to use different approaches in the field of personality neuroscience To gain deeper insight into the basis of personality traits does not only require to consider genetic as well as environmental influences and their interplay, but also requires more differentiated statistical analyses that can at least in part tackle the often inconsistent findings in this field

/pdf/intellectual-investment-dopaminergic-gene-variation-and-life-3ql0lm2s77.pdf

Kristin Anacker

Papers

No association between dopamine D4 receptor gene exon III and -521C/T polymorphism and novelty seeking.

Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3

Dopamine D4 receptor gene variation impacts self-reported altruism.

Cognitive Engagement Mediates the Relationship between Positive Life Events and Positive Emotionality.

Intellectual Investment, Dopaminergic Gene Variation, and Life Events: A Critical Examination.