Epigenetics and the Biological Basis of Gene x Environment Interactions
ABSTRACT Child and adolescent psychiatry is rife with examples of the sustained effects of early experience on brain function. The study of behavioral genetics provides evidence for a relation between genomic variation and personality and with the risk for psychopathology. A pressing challenge is that of conceptually integrating findings from genetics into the study of personality without regressing to arguments concerning the relative importance of genomic variation versus nongenomic or environmental influences.
Epigenetics refers to functionally relevant modifications to the genome that do not involve a change in nucleotide sequence. This review examines epigenetics as a candidate biological mechanism for gene x environment interactions, with a focus on environmental influences that occur during early life and that yield sustained effects on neural development and function.
The studies reviewed suggest that epigenetic remodeling occurs in response to the environmental activation of cellular signalling pathways associated with synaptic plasticity, epigenetic marks are actively remodeled during early development in response to environmental events that regulate neural development and function, and epigenetic marks are subject to remodeling by environmental influences even at later stages in development.
Epigenetic remodeling might serve as an ideal mechanism for phenotypic plasticity--the process whereby the environment interacts with the genome to produce individual differences in the expression of specific traits.
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- "In particular, the Novosibirsk group has long argued that hormonal states in the mother, associated with the less stressful conditions of domesticity, are involved in generating the DS (Belyaev 1979; Trut et al. 2004, 2009). Findings consistent with this idea, though opposite in effect, involve maternal stresses in mice that create epigenetic chromatin state changes and behavioral phenotypes in offspring (Meany and Szyf 2005; Bagot and Meaney 2010). Whether epimutations have the requisite stability in transgenerational transmission to generate true heritable states is always a key question about their evolutionary potential (Slatkin 2009) but strong trans-generational transmissibility of epigenetic states has been shown for two genes affecting coat color patterns in the mouse, Agouti and Axin Fu genes (Morgan et al. 1999; Rakyan et al. 2003). "
ABSTRACT: Charles Darwin, while trying to devise a general theory of heredity from the observations of animal and plant breeders, discovered that domesticated mammals possess a distinctive and unusual suite of heritable traits not seen in their wild progenitors. Some of these traits also appear in domesticated birds and fish. The origin of Darwin's "domestication syndrome" has remained a conundrum for more than 140 years. Most explanations focus on particular traits, while neglecting others, or on the possible selective factors involved in domestication rather than the underlying developmental and genetic causes of these traits. Here, we propose that the domestication syndrome results predominantly from mild neural crest cell deficits during embryonic development. Most of the modified traits, both morphological and physiological, can be readily explained as direct consequences of such deficiencies, while other traits are explicable as indirect consequences. We first show how the hypothesis can account for the multiple, apparently unrelated traits of the syndrome and then explore its genetic dimensions and predictions, reviewing the available genetic evidence. The article concludes with a brief discussion of some genetic and developmental questions raised by the idea, along with specific predictions and experimental tests.Genetics 07/2014; 197(3):795-808. DOI:10.1534/genetics.114.165423 · 4.87 Impact Factor
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- "Animal models have shown that non-attentive care in rats is an environmental epigenetic factor that can negatively affect gene expression in their offspring . However, research has also shown that these negative effects can be reversed with a good maternal care . Results such as these generate a hope that psychological programs, designed to sensitize neglectful mothers to infant signals, can reverse the devastating effects of their lack of affection with their babies. "
ABSTRACT: Results illustrating an atypical neural processing in the early and late differentiation of infant faces have been obtained with neglectful mothers. The present study explores whether a different pattern of response is observed when using non-infant affective pictures. We examined the event-related evoked potentials and induced delta, theta and alpha activity in 14 neglectful mothers and 14 control mothers elicited while categorizing positive, negative and neutral pictures from the International Affective Picture System. Self-reports of anhedonia and empathy were also recorded. Early posterior negativity, P200 and late positive potential components were modulated by the emotional content of pictures in both groups. However, the LPP waveform had a more delayed and more attenuated maximum in neglectful mothers than in control mothers. Oscillatory responses indicated lower power increases for neglectful mothers than for control mothers in delta (1-4 Hz), theta (4-8 Hz) and lower alpha (8-10 Hz) bands at frontal sites, and a more consistent increase for neglectful mothers in theta and lower alpha bands at occipital sites, especially for negative pictures. These findings help us to better understand the limits of emotional insensitivity in neglectful mothers.PLoS ONE 01/2014; 9(1):e87808. DOI:10.1371/journal.pone.0087808 · 3.23 Impact Factor
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- "At the least, it can be suggested that platelet serotonin levels might offer a potential predictor of an autism behavioral phenotype in WBS. It might also be of interest that epigenetic mechanisms involving gene X environment interactions and effects on the serotoninergic system  have been found in several genetic syndromes associated with autism spectrum disorders . Further studies on gene X environment interactions, including epigenetic mechanisms, are necessary to better understand the association between common WBSCR deletions and typical autistic behavioral and neurochemical phenotypes. "
ABSTRACT: Deletion of the Williams-Beuren syndrome (WBS) critical region (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by hypersociability and excessive talkativeness and often considered the opposite behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in expressive language. Gene--dosage effects on language development at 7q11.23 have been hypothesized. Molecular characterization of the WBSCR was performed by fluorescence in situ hybridization and high-resolution single-nucleotide polymorphism array in two individuals with severe autism enrolled in a genetic study of autism who showed typical WBS facial dysmorphism on systematic clinical genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR, locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6-sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes were examined. The two patients had common WBSCR deletions between proximal and medial low copy repeat clusters, met diagnostic criteria for autism and displayed severe impairment in communication, including a total absence of expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited platelet hyperserotonemia and low melatonin production. Our observations indicate that behaviors and neurochemical phenotypes typically associated with autism can occur in patients with common WBSCR deletions. The results raise intriguing questions about phenotypic heterogeneity in WBS and regarding genetic and/or environmental factors interacting with specific genes at 7q11.23 sensitive to dosage alterations that can influence the development of social communication skills. Thus, the influence of WBSCR genes on social communication expression might be dramatically modified by other genes, such as 5-HTTLPR, known to influence the severity of social communication impairments in autism, or by environmental factors, such as hyperserotonemia, given that hyperserotonemia is found in WBS associated with autism but not in WBS without autism. In this regard, WBS provides a potentially fruitful model with which to develop integrated genetic, cognitive, behavioral and neurochemical approaches to study genotype--phenotype correlations, possible gene--environment interactions and genetic background effects. The results underscore the importance of considering careful clinical and molecular genetic examination of individuals diagnosed with autism.Molecular Autism 08/2013; 4(1):29. DOI:10.1186/2040-2392-4-29 · 5.49 Impact Factor