Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within-group heterogeneity

Yildirim, Bariş O.; Derksen, J.J.L.

doi:10.1016/j.psychres.2015.07.005

Cited by 14 publications

(13 citation statements)

References 734 publications

(1,004 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD and ASPD). Overall, these findings are consistent with genetic studies implicating DRD4 in externalizing psychiatric symptoms and substance use (Ptacek et al, ), as well as CU and psychopathic traits (Yildirim & Derksen, ). In part, these shared associations may reflect the role of dopamine signaling in processes that are common to multiple externalizing problems, such as sensation‐seeking, impulsivity, and reward processing (Beauchaine & McNulty, ).…”

Section: Discussionsupporting

confidence: 87%

DRD4 methylation as a potential biomarker for physical aggression: An epigenome‐wide, cross‐tissue investigation

Cecil

Walton

Pingault

et al. 2018

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Epigenetic processes that regulate gene expression, such as DNA methylation (DNAm), have been linked to individual differences in physical aggression. Yet, it is currently unclear whether:(a) DNAm patterns in humans associate with physical aggression independently of other cooccurring psychiatric and behavioral symptoms; (b) whether these patterns are observable across multiple tissues; and (c) whether they may function as a causal versus noncausal biomarker of physical aggression. Here, we used a multisample, cross-tissue design to address these questions. First, we examined genome-wide DNAm patterns (buccal swabs; Illumina 450k) associated with engagement in physical fights in a sample of high-risk youth (n = 119; age = 16-24 years; 53% female). We identified one differentially methylated region in DRD4, which survived genome-wide correction, associated with physical aggression above and beyond co-occurring symptomatology (e.g., ADHD, substance use), and showed strong cross-tissue concordance with both blood and brain. Second, we found that DNAm sites within this region were also differentially methylated in an independent sample of young adults, between individuals with a history of chronic-high versus low physical aggression (peripheral T cells; ages 26-28). Finally, we ran a Mendelian randomization analysis using GWAS data from the EAGLE consortium to test for a causal association of DRD4 methylation with physical aggression. Only one genetic instrument was eligible for the analysis, and results provided no evidence for a causal association. Overall, our findings lend support for peripheral DRD4 methylation as a potential biomarker of physically aggressive behavior, with no evidence yet of a causal relationship. K E Y W O R D S DNA methylation, DRD4, externalizing problems, Mendelian randomization, physical aggression, replication † Co-senior authors.

show abstract

Section: Discussionsupporting

confidence: 87%

DRD4 methylation as a potential biomarker for physical aggression: An epigenome‐wide, cross‐tissue investigation

Cecil

Walton

Pingault

et al. 2018

American J of Med Genetics Pt B

View full text Add to dashboard Cite

show abstract

“…Reward circuit hyperconnectivity reported here might thus reflect a hyperfunctioning reward system, which in theory could fuel an interpersonal style dominated by rewards and personal gains. Individuals with psychopathic traits are indeed prone to manipulate and deceive others to satisfy their excessive reward dependence and need for personal gains, largely driven by reward system hyperfunctionality [Bjork et al, 2012; Pujara et al, 2014; Seara‐Cardoso and Viding, 2014; Yildirim and Derksen, 2015]. Our finding, however, may equally well allude to intrinsically heightened threshold for activating the reward system (i.e., hyporesponsivity), which could actually diminish reward sensitivity in some cases.…”

Section: Discussionmentioning

confidence: 99%

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Aghajani

Colins

Klapwijk

et al. 2016

Human Brain Mapping

View full text Add to dashboard Cite

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit‐level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct‐disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait‐specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self‐centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017–4033, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

show abstract

“…Lower availability of dopamine at the prefrontal level seems to be associated with higher ability to change mental representations and higher mental flexibilityyet, lower emotional sensitivity. This biochemical scenario can lead to higher ability to make action plans (Yildirim & Derksen, 2015).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that antisocial individuals, having the Met/Met genotype, may present stable cognitive performance and preserved emotional functioning, but lower resistance to emotional stress, being more sensitive to social rejection and to the need of reward (Yildirim & Derksen, 2015). On the other hand, it has also been proposed that antisocial individuals with the Val/Val genotype would show reduced cognitive performance, emotional insensitivity, higher resistance to emotional stress, and insensitivity to social rejection and reward (Yildirim & Derksen, 2015). These theoretical proposals may suggest that antisocial individuals with the Val/Val genotype may display more psychopathic personality traits related to emotional insensitivity measured by the facets interpersonal (F1) and affective (F2) of the Psychopathic Checklist-Revised (PCL-R) (Hare, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association between S-COMT activity and impulsive and premeditated aggression in a population of violent offenders: preliminary results of a cross sectional study

et al. 2022

View full text Add to dashboard Cite

Aggression can be conceptualised as a physical act towards another person, verbal offenses, destructive acts towards objects, and self-inflicted harmful acts. It is highly frequent in the context of Antisocial Personality Disorder (ASPD) and has been correlated to disturbances in the dopaminergic system. In the prefrontal cortex, the dopamine metabolism depends on catechol-O-methyltransferase (COMT). DRD2 receptors also play a role in the expression of aggression by modulating dopamine metabolism, in the striatum. In this study, we evaluated the association between COMT activity and type of aggression, in a sample of violent male offenders. Participants were subjected to sociodemographic, clinical, and psychometric evaluation through standardised instruments. Erythrocyte S-COMT activity was measured, and COMT and the DRD2 genotypes were analysed. Individuals displaying impulsive aggression showed lower S-COMT erythrocyte activity (p=0.026) and lower frequency of Val/Val (rs4680) genotype than individuals with premeditated aggression (p=0.047). S-COMT erythrocyte activity was positively correlated with the PCL-R total score (r=0.34; p=0.018). In conclusion, our preliminary results indicate that COMT can be associated to different aggression types in violent offenders, and it can represent a possible pharmacological target for the treatment of impulsive and premeditated aggression, in incarcerated patients.

show abstract

Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within-group heterogeneity

Cited by 14 publications

References 734 publications

DRD4 methylation as a potential biomarker for physical aggression: An epigenome‐wide, cross‐tissue investigation

DRD4 methylation as a potential biomarker for physical aggression: An epigenome‐wide, cross‐tissue investigation

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Association between S-COMT activity and impulsive and premeditated aggression in a population of violent offenders: preliminary results of a cross sectional study

Contact Info

Product

Resources

About