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.
Highlights
Epigenetics is the study of mitotically and/or meiotically heritable changes in gene function that are not explained by changes in DNA sequence [1]
The results of human and nonhuman animal studies have suggested that early-life adversity can lead to epigenetic regulation of genes involved in stress-response, behavioral disinhibition and cognitive-emotional systems
Turecki et al [241] have described how early-life adversity increases risk of suicide in susceptible individuals by disrupting the development of stable emotional, behavioral and cognitive phenotypes that are likely to result from the epigenetic regulation of the hypothalamic-pituitary-adrenal axis and other systems involved in responses to chronic or acute traumatic stress
Summary
Epigenetics is the study of mitotically and/or meiotically heritable changes in gene function that are not explained by changes in DNA sequence [1]. Adverse early-life circumstance is associated with disturbances in normal brain development [43], with maternal care influencing HPA stress responses through tissue-specific effects on gene transcription and epigenetic regulation of glucocorticoid receptor expression [5355]. Hefurther hypothesized that follow-up gene research in this area, albeit premature, resulting in confirmation of positive correlations with dopaminergic polymorphisms, and utilizing highly screened controls (eliminating any addictive, compulsive, and impulsive behaviors in both proband and family) may have important ramifications in our young population This concept has been confirmed by additional work by Vaske et al [143] showing that offenders, on average, are more likely to be violently victimized than non offenders. These findings provided further evidence of gene-by-environment interaction in the context of differential susceptibility to institutionalized, adverse care environments [238, 239]
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