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- Archer, Trevor, 1949, et al.
(författare)
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Epigenetics in Developmental Disorder: ADHD and Endophenotypes.
- 2011
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Ingår i: Journal of genetic syndrome & gene therapy. - 2157-7412. ; 2:104
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Tidskriftsartikel (refereegranskat)abstract
- Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the "drug response phenotype," rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring.
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| 2. |
- Archer, Trevor, 1949, et al.
(författare)
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Neurogenetics and Epigenetics in Impulsive Behaviour: Impact on Reward Circuitry.
- 2012
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Ingår i: Journal of genetic syndrome & gene therapy. - : OMICS Publishing Group. - 2157-7412. ; 3:3
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Forskningsöversikt (refereegranskat)abstract
- Adverse, unfavourable life conditions, particularly during early life stages and infancy, can lead to epigenetic regulation of genes involved in stress-response, behavioral disinhibition, and cognitive-emotional systems. Over time, the ultimate final outcome can be expressed through behaviors bedeviled by problems with impulse control, such as eating disorders, alcoholism, and indiscriminate social behavior. While many reward gene polymorphisms are involved in impulsive behaviors, a polymorphism by itself may not translate to the development of a particular behavioral disorder unless it is impacted by epigenetic effects. Brain-derived neurotrophic factor (BDNF) affects the development and integrity of the noradrenergic, dopaminergic, serotonergic, glutamatergic, and cholinergic neurotransmitter systems, and plasma levels of the neurotrophin are associated with both cognitive and aggressive impulsiveness. Epigenetic mechanisms associated with a multitude of environmental factors, including premature birth, low birth weight, prenatal tobacco exposure, non-intact family, young maternal age at birth of the target child, paternal history of antisocial behavior, and maternal depression, alter the developmental trajectories for several neuropsychiatric disorders. These mechanisms affect brain development and integrity at several levels that determine structure and function in resolving the final behavioral expressions.
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