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2014 ; 426
(20
): 3389-412
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Epigenetic signaling in psychiatric disorders
#MMPMID24709417
Peña CJ
; Bagot RC
; Labonté B
; Nestler EJ
J Mol Biol
2014[Oct]; 426
(20
): 3389-412
PMID24709417
show ga
Psychiatric disorders are complex multifactorial illnesses involving chronic
alterations in neural circuit structure and function. While genetic factors are
important in the etiology of disorders such as depression and addiction,
relatively high rates of discordance among identical twins clearly indicate the
importance of additional mechanisms. Environmental factors such as stress or
prior drug exposure are known to play a role in the onset of these illnesses.
Such exposure to environmental insults induces stable changes in gene expression,
neural circuit function, and ultimately behavior, and these maladaptations appear
distinct between developmental and adult exposures. Increasing evidence indicates
that these sustained abnormalities are maintained by epigenetic modifications in
specific brain regions. Indeed, transcriptional dysregulation and associated
aberrant epigenetic regulation is a unifying theme in psychiatric disorders.
Aspects of depression and addiction can be modeled in animals by inducing
disease-like states through environmental manipulations (e.g., chronic stress,
drug administration). Understanding how environmental factors recruit the
epigenetic machinery in animal models reveals new insight into disease mechanisms
in humans.
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