Gene × Environment effects of serotonin transporter, dopamine receptor D4, and monoamine oxidase A genes with contextual and parenting risk factors on symptoms of oppositional defiant disorder, anxiety, and depression in a community sample of 4-year-old children

Lavigne, John V.; Herzing, Laura B. K.; Cook, Edwin H.; LeBailly, Susan A.; Gouze, Karen R.; Hopkins, Joyce; Bryant, Fred B.

doi:10.1017/s0954579412001241

Cited by 52 publications

(49 citation statements)

References 126 publications

(226 reference statements)

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“…There have been a number of studies of MAOA VNTR polymorphisms as risk factors for MDD, but metaanalysis confirmed this association only in Asian populations (Fan et al, 2010). In preschool boys (N=97), increased caregiver depression or family conflict was associated with increased depression symptoms in boys with low-MAOA polymorphism genotypes (Lavigne et al, 2013). Our study did not use an animal model of a childhood behavior disorder, but, using the RDoC framework for integrating basic research and diagnostic criteria (Garvey et al, 2016; Cuthbert and Insel, 2013; Maestripieri and Lilienfeld, 2016), the results can be seen applicable to the “negative valence” construct dimension relevant to depression, as well as other developmental diagnoses.…”

Section: 0 Discussionmentioning

confidence: 99%

Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions

Golub

Hogrefe

Bulleri

2016

European Neuropsychopharmacology

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Juvenile male rhesus macaques received therapeutic doses of fluoxetine daily from one to three years of age and were compared to vehicle-treated controls (N=16/group). Genotyping for monoamine oxidase A (MAOA) polymorphisms was used to form subgroups (N=8) with high and low expression of the gene. Behavioral responses were scored during 30-second exposures to pictures differing in affective content. As expected from its therapeutic effect, fluoxetine decreased the behavioral response to emotionally evocative pictures. A 44% reduction in number of expressive behaviors was seen, but only in subjects with low expression MAOA polymorphisms. In general, this effect occurred for pictures of varying affective content and was not due to altered occurrence of one specific behavior or type of behavior. The drug*genotype interaction was seen after one and two years of treatment and did not reverse one year after discontinuation of dosing. Two potential translational implications are suggested: (1) MAOA genetic polymorphisms may be the source of some of the variability in response to fluoxetine treatment in children; (2) extended fluoxetine treatment during juvenile brain development may result in persistent effects on emotional regulation.

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Section: 0 Discussionmentioning

confidence: 99%

Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions

Golub

Hogrefe

Bulleri

2016

European Neuropsychopharmacology

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“…Levels of MAO-A in the brain of patients with major depressive disorder, measured using positron emission tomography (PET), are elevated by an average of 34 %. Recently, evidence has indicated that the MAOA gene may associate with depression [49] and stress [50]. Evidence regarding whether lower or higher transcriptional efficiency of the MAOA gene, is positively associated with psychological pathology, has however, been mixed.…”

Section: Monoamine Oxidase-amentioning

confidence: 99%

Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome (RDS)

et al. 2014

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We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined “Reward Deficiency Syndrome” (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS™) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.

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“…47 Specifically, dopamine receptor and dopamine pathway, serotonin transporter, and COMT genetic variants interact with environmental factors to influence cognitive and behavioral functioning in various childhood populations. 18,48-58 Although the higher activity enzyme genotype (GG) is generally associated with a reduction in executive cognition, it is also associated with better stress resiliency, indicating that stressful environmental factors may overwhelm the direct effects the COMT genotype has on cognition 59 Because a TBI often leads to increased family burden 42,60,61 , the potential stress resiliency effects of the high activity genotype (GG) may outweigh the effects on executive cognition. Future studies should evaluate the interaction of genetics and environmental and other factors on recovery.…”

Section: Discussionmentioning

confidence: 99%

Influence of Catechol-O-methyltransferase on Executive Functioning Longitudinally After Early Childhood Traumatic Brain Injury

Kurowski

Backeljauw

Zang

et al. 2016

Journal of Head Trauma Rehabilitation

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Objective To elucidate the association of a functional catechol-O-methyltransferase (COMT) genotype (rs4680) with recovery of executive functions up to 18 months after early childhood traumatic brain injury (TBI) compared to an orthopedic injury (OI) group. Setting Outpatient Participants 134 children with a moderate to severe TBI (n=63) or OI (n=71) between the ages of 3-6 years who were followed 18 months post-injury Design Case-comparison, longitudinal cohort Main Measures The Behavior Rating Inventory of Executive Function (BRIEF), developmental neuropsychological assessment (NEPSY) of verbal fluency (VF), and a modified Stroop Test for young children (Shape School) Results The low activity COMT enzyme genotype (AA) was associated with better scores on the NEPSY VF (F=3.80, p=.02) and the Shape School (F=2.89, p =.06) in all participants when controlling for injury type (TBI vs. OI) over the first 18 months after injury. Injury type (TBI vs. OI) did not significantly moderate the effect of the COMT genotypes on executive function recovery. Conclusion This study provides preliminary evidence for a role of COMT genotypes in long-term recovery of executive function after pediatric TBI and OI. Larger studies are needed to determine the exact link between genetic variation in the COMT gene and TBI recovery in children.

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Gene × Environment effects of serotonin transporter, dopamine receptor D4, and monoamine oxidase A genes with contextual and parenting risk factors on symptoms of oppositional defiant disorder, anxiety, and depression in a community sample of 4-year-old children

Cited by 52 publications

References 126 publications

Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions

Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions

Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome (RDS)

Influence of Catechol-O-methyltransferase on Executive Functioning Longitudinally After Early Childhood Traumatic Brain Injury

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