Dopaminergic system genes in childhood aggression: Possible role for DRD2

Zai, Clement C.; Ehtesham, Sahar; Choi, Esther; Nowrouzi, Behdin; Luca, Vincenzo De; Stankovich, Larisa; Davidge, Kristen M.; Freeman, Natalie; King, Nicole; Kennedy, James L.; Beitchman, Joseph H.

doi:10.3109/15622975.2010.543431

Cited by 68 publications

(36 citation statements)

References 81 publications

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“…In agreement, A1-allele carriers display higher levels of childhood antisocial behavior, bipolar disorder with low anxiety, impulsivity, novelty/stimulus seeking, aggression, antisocial/borderline traits, faster habituation to positive feedback (decoupling behavior from experience), and substance abuse/dependence but also adaptive traits such as extraversion, behavioral activation, low depression or harm avoidance, and improved cognitive performance (Noble et al, 1998;Bartrés-Faz et al, 2002;Eisenberg et al, 2007;Hoenicka et al, 2007;Ponce et al, 2008 ;Althaus et al, 2009;Esposito-Smythers et al, 2009;Ponce et al, 2009;Barskiĭ et al, 2010;Nemoda et al, 2010;Smillie et al, 2010;Stelzel et al, 2010;Thaler et al, 2012;Kazantseva et al, 2011;Lu et al, 2012;Zai et al, 2012;Wang et al, 2013aWang et al, , 2014. A1-carriers also showed significantly lower levels of risk for depression and higher engagement bias towards positive social stimuli, thus evincing a more stable and higher DA functioning (Elovainio et al, 2007;Gong et al, 2013).…”

Section: Da Receptor Configuration (D2-receptors)mentioning

confidence: 74%

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

Yildirim

Derksen

2015

Psychiatry Research

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Section: Da Receptor Configuration (D2-receptors)mentioning

confidence: 74%

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

Yildirim

Derksen

2015

Psychiatry Research

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“…Since that time there have been no less than 3738 (Pubmed-6-23-14) peer reviewed articles on many peripheral and central nervous system (CNS) behaviors and physiological processes. Understandably addiction or even the broader term RDS involves very complex gene × environment interaction and one cannot expect that a single gene like the DRD2 gene would have a powerful effect by itself, however, albeit many negative findings, there is still a plethora of evidence for the role of the DRD2 gene polymorphisms and a number (small sample of studies represented herein) of addictive and other reward dependent behaviors including: alcohol dependence (Pato et al, 1993; Ponce et al, 2003; Munafò et al, 2007; Smith et al, 2008; Pinto et al, 2009; Grzywacz et al, 2012; Wang et al, 2013); drug dependence (Li et al, 2004; Xu et al, 2004; Young et al, 2004; Barratt et al, 2006; Li et al, 2006; Hou and Li, 2009; Chen et al, 2011a,b; Al-Eitan et al, 2012; Jacobs et al, 2013; Lee et al, 2013; Ohmoto et al, 2013; Sullivan et al, 2013; Suraj Singh et al, 2013; Vereczkei et al, 2013; Wang et al, 2013; Clarke et al, 2014; Roussotte et al, 2014; Schuck et al, 2014); mood disorders (Vaske et al, 2009; Huertas et al, 2010; Zhu et al, 2011; Zou et al, 2012; Hettinger et al, 2012; Jutras-Aswad et al, 2012; Tsuchimine et al, 2012; Whitmer and Gotlib, 2012; Zai et al, 2012; Peciña et al, 2013; Zhang et al, 2014); rearing behaviors (Mills-Koonce et al, 2007; Bakermans-Kranenburg and van Ijzendoorn, 2011; Beaver and Belsky, 2012; Masarik et al, 2014); obesity (Spangler et al, 2004; Fang et al, 2005; Huang et al, 2005; Epstein et al, 2007; Nisoli et al, 2007; Barnard et al, 2008; Blum et al, 2008; Eny et al, 2009; Epstein et al, 2010; Mathes et al, 2010; Stice et al, 2010; van Strien et al, 2010; Jabłoński, 2011; Anitha et al, 2012; Chen et al, 2012; Winkler et al, 2012; Ariza et al, 2013; Car...…”

Section: Controversial Findingsmentioning

confidence: 99%

Dopamine and glucose, obesity, and reward deficiency syndrome

2014

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Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain’s production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization of powerful dopamine D2 agonists have failed due to chronic down regulation of D2 receptors newer targets based on novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of reward deficiency.

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“…Children with behavioral problems were referred from the Centre for Addiction and Mental Health as well as Youthdale Treatment Centres to our research coordinator, who subsequently contacted the families [Zai et al, 2012]. After receiving their consent to participate in the study, the research coordinator met with both parents and subjects and administered the questionnaires.…”

Section: Samplesmentioning

confidence: 99%

Study of the Catechol‐O‐Methyltransferase (COMT) Gene with High Aggression in Children

Hirata

Zai

Nowrouzi

et al. 2012

Aggressive Behavior

Self Cite

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The etiology of childhood-onset aggression (COA) is poorly understood, but early COA can be considered as a strong risk factor for adult delinquency and criminal behavior. Callous-unemotional (CU) traits have been proposed as a developmental model of antisocial behavior. Catechol O-methyltransferase (COMT) has been associated with aggression, attention deficit/hyperactivity disorder (ADHD), and other psychiatric disorders. We report an association study between COMT single-nucleotide polymorphisms (SNPs), childhood aggression, and the CU trait in our sample of 144 children with scores at or exceeding the 90th percentile on the aggression subscale of the parent-reported Child Behavior Checklist and the Teacher's Report Form. The genotype analysis of rs6269 showed nominally significant association (P = .019) and rs4818 showed a trend (P = .064) with COA. Trends were observed for rs6269 and rs4818 with CU scores (P < .10) as well. The analyses stratified by ADHD, or gender showed no significant results. This is the first report to our knowledge evaluating COMT SNPs with the phenotype of high aggression in children with a possible role for the COMT marker in CU traits. Given the importance of CU traits in antisocial behavior, further investigation of COMT is warranted.

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Dopaminergic system genes in childhood aggression: Possible role for DRD2

Abstract: Our preliminary results suggest that three polymorphisms in DRD2 are associated with childhood aggression. Future studies are required to replicate the current results and to further explore the relationship between the dopamine system and aggressive behaviour in children.

Cited by 68 publications

References 81 publications

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

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

Dopamine and glucose, obesity, and reward deficiency syndrome

Study of the Catechol‐O‐Methyltransferase (COMT) Gene with High Aggression in Children

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