First of all, some reminders of genetics can be helpful. Genetic information is carried by nucleotides. Bound to each other, they form a strand of DNA (deoxyribonucleic acid) which, helically wound with a second complementary strand, forms a DNA molecule. This molecule, associated with proteins, constitutes a chromosome, and a group of chromosomes is named chromatin. A gene is a portion of a chromosome: it is an elementary unit of the genetic information that codes for a characteristic. The result of the expression of the genes is called the phenotype: it is the whole of the characteristics of an individual. The entire genetic material of an individual is called the genome.
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Introduction
It used to be considered that genes, passed down from one generation to the next, determined the characteristics of each individual without any influence of the environment (Lambert, 2014).
The first sequencing of the human genome, completed in 2003, brought to light a paradox well-known in genetics: all our cells contain in their nuclei our entire genetic heritage, but they specialize during our development and can become completely different. This event, among others, renewed interest in a concept that is not so recent: epigenetics. Waddington spoke of an epigenetic landscape for the first time in 1942, in which he described the complex mechanisms between the environment and the genes that modulate their expression. So, epigenetics is the study of changes in gene activity (Monhonval & Lotstra, 2014), changes that do not involve modification in the DNA sequence and may be reversible. More clearly, according to epigenetics, it seems that genetic factors and environmental factors play a role in development interactively (Lambert, 2014).
Epigenetics mechanisms
A cell constantly receives signals about what surrounds it. These signals inform the cell about its specialization during its development, but also about the necessary modifications of its activity according to the situations (Inserm, 2015). They can come from the environment in every sense: the internal environment, neighbouring cells for example; but also from the external environment, our life experiences, our food, the presence of stress etc. Whatever their origins, all these signals are likely to create biochemical marks in the chromatin, without modification of the nucleotide sequence of DNA (Lambert, 2014). These epigenetic fingerprints will play a regulatory role: they will promote or inhibit the expression of genes.
For information, the epigenetic mechanisms most studied in psychiatry are histone acetylation, DNA methylation, and non-coding RNAs. If you have good knowledge of genetics, you can look at how these mechanisms work, but they will not be detailed here because they are too complicated.
Transmissibility
Epigenetic marks are transmitted during cellular divisions: this is what keeps the specialization of cells during development. But can they be passed from one generation to another? It has been shown several times that intergenerational transmission of acquired traits is possible. This transmission can be done in two different ways: either by behavioral exposure or through germ cells.
Weaver’s experience (2007, cited by Monhonval & Lotstra, 2014) is a good illustration of the concept of transmission through behavioral exposure. He showed that the quality of maternal care in rats (evaluated in terms of licking and grooming) could change the DNA methylation of the raccoons. This epigenetic modification in progeny being persistent, once in adulthood, the females had the same methylation profile as their mother and thus provided the same types of care to their progeny. In this way, they reproduced again the same methylation profile on the new generation.
Transmission via germ cells is subject to much debate. Indeed, epigenetic fingerprints are supposed to be erased during gametogenesis (process of formation of reproductive cells) and at the beginning of embryogenesis (process of formation of an organism from a zygote), so they are not supposed to pass from one generation to another (Inserm, 2015). However, it seems that some marks persist. The experience of Dias and Ressler (2014) is an example of intergenerational transmission of acquired traits. The authors set up olfactory conditioning to fear in post-conception mice and observed, in the next generation, increased sensitivity to the smell of fear but not to other odors. To verify that it was not a social transmission, they repeated the same experiment by practicing in vitro fertilization and the results were the same. What they observed was, therefore, transmission via germ cells.
Epigenetics and psychopathology
The potential transmissibility of epigenetic marks from one generation to another has aroused interest in the world of psychiatry over the last decade. In this way, many studies have tried to make the link between epigenetics and psychopathology.
For the moment, the published results have not been confirmed by enough further studies. Indeed, researchers encounter many difficulties: the complexity of experimental models, the time required to raise several generations of subjects and the need for multidisciplinary knowledge to understand the phenomena involved.
From a clinical point of view, epigenetics could challenge many of the theories, classifications, and practices currently used. The possible reversibility of epigenetic marks makes sense with the notion of resilience: if this reversibility becomes established, the interest of early psychopathological care would greatly increase.
Perspectives and limits
The vision of genetic material is becoming more flexible to integrate this notion of epigenetics. It has many hopes and potential applications. Some authors believe that new technologies will “undoubtedly in the near future identify epigenetic mechanisms involved in the development of psychiatric diseases” (Bale et al., 2010, quoted by Gonon & Moisan, 2013).
Nevertheless, this excess of optimism is still nuanced. First of all, it is necessary to remember that a vast majority of the results published at present are based on animals, not on humans. Moreover, the understanding of epigenetic mechanisms is still in its early stages, suggesting that in the coming years, many current results could be refuted by new studies. Finally, the complexity of epigenetic mechanisms implies that the path to their complete comprehension will be extremely long (Gonon & Moisan, 2013).
By Anne-Charlotte Nasles, M2 PCPI
Keywords
Epigenetics
Genetic factors and environmental factors
Gene activity
Transmission
Reversibility
Words I have learned
In every sense: au sens large
Fingerprint: empreinte
Licking: léchage
Grooming: toilettage
To arouse: susciter
Early stages: balbutiements
References
Dias, B. G., & Ressler, K. J. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience, 17(1), 89-96.
Gonon, F., & Moisan, M. P. (2013). L’épigénétique, la nouvelle biologie de l’histoire individuelle ?. Revue française des affaires sociales, 1(1-2), 21-31.
Inserm. (2015). Epigénétique. Retrieved on http://www.inserm.fr/thematiques/genetique-genomique-et-bioinformatique/dossiers-d-information/epigenetique
Lambert, N. (2014). Génétique et transmission transgénérationnelle. Cahiers de psychologie clinique, 2(43), 11-28.
Monhonval, P., & Lotstra, F. (2014). Transmission transgénérationnelle des traits acquis par l’épigénétique. Cahiers de psychologie clinique, 2(43), 29-42.