Epigenetics has been referred to as a “second, largely secret code” (Kramer 2005). In 2003, Europe organized a “human epigenome project” and in 2004, the Center for Epigenetics of Common Human Disease was established at Johns Hopkins University . Kramer (2005) has defined epigenetics as “the study of stable alterations in gene expression by nongenetic mechanisms [I would say processes] resulting in stable alterations in phenotype” (p. 25). In a deep sense, epigenetics is a form of biological or environmental programming in which the mother transmits to the offspring a form of forecasting of likely environmental conditions to be faced by the latter.
Weaver et al (2004) used a within-series cross-fostering model and a behavior system in rats in which high licking grooming (LG) arched-back nursing (ABN) mothers were compared with low LG-ABN mothers. The offspring of high LG-ABN are less anxious and fearful as adults and have attenuated limbic-hypothalamic-pituitary-adrenal axis (LHPA) responses to stress/challenge than offspring of mothers with low rates of LG-ABN. However, cross-fostering the offspring of high and low LG-ABN mothers within 12 hours of birth produced adult rats with the stress response patterns associated with their foster-rearing mothers. Evidence that gene expression in the LHPA axis of the offspring was modified is demonstrated by increased glucocorticoid receptor (GR) mRNA in the offspring of high LG-ABN mothers. This is exactly what we see in schizophrenia research as demonstrated by Pekka Tienari and colleagues in Finland, i.e., only those offspring of high risk mothers, i.e., biological mothers diagnosed with schizophrenia, developed a schizophrenia spectrum disorder who were raised in familial settings blindly rated as dysfunctional on a multiplicity of measures (this was a large double-blind controlled study). Tienari concluded that the research results demonstrate genetic control of sensitivity to the environment or environmental control of gene expression.
Weaver et al (2004) successfully demonstrated that epigenetic alterations in pup offspring were correlated with the physiological and behavioral differences in gene expression. The alterations occurred in chromatin structure at a GR gene promotor in the hippocampus. Stable variations in gene expression are correlated with methylation of DNA. Cross-fostering produced C-methylation changes consistent with the maternal behavior of the rearing mother. Pharmacologic reversibility can be achieved by infusion of a histone deacetylase inhibitor. A potential process operating within the conceptual space between the genome and environment is therefore available to explain the stable alterations in gene expression that result from gene-environment interaction, and at the human level, the gene-environmental interaction as subjectively experienced, perceived, interpreted and acted upon. Weaver et al (2004) concluded: “We propose that effects on chromatin structure [DNA, RNA, protein, etc] such as those described here serve as an intermediate process that imprints dynamic environmental experiences on the fixed genome, resulting in stable alterations in phenotype.”
The implications of this research in epigenetics for mental health clinicians and psychotherapists is quite significant. It definitely makes a case for long-term treatments whose goals are to effect more secure attachments and affect regulation. I finally can say with good scientific research to validate my long-standing aversion to the often quoted aphorism that behind every twisted thought is a twisted molecule: behind every twisted thought may very well be a twisted feeling/affect arising from a forecasted or actual twisted environment. Genes, in the field of psychiatry, are rarely destiny. They, as neurons, are as dynamic as the environments in which they are embedded. Neurogenetic and neurobiological reductionism in psychiatry is scientifically challenged and found to be an invalid model of the complex psychosociobiological syndromes and acute/chronic reaction patterns catalogued in DSM.
References
Weaver, IC, Cervoni, N, Champagne , FA et al (2004). Epigenetic programming by maternal behavior. Nature Neuroscience 7: 847-854.
Kramer, DA. (2005). Commentary: Gene-environment interplay in the context of genetics, epigenetics, and gene expression. J. Am. Acad. Child Adolesc. Psychiatry, 44:1, 19-27.
Brian Koehler PhD
New York University
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