Читать книгу Abnormal Psychology - William J. Ray - Страница 100

One basic idea from Mendelian genetics was that genes are not changed by experience. What is passed on, except in the case of damage to the gene, is exactly the same gene that was received by the organism from its parents. This came to be called the central dogma of molecular biology as described by Francis Crick. He basically stated that information flow was one-directional. That is, it went from the gene to the protein. What came to be called reverse translation was seen as impossible. Thus, the gene could not be influenced or changed by changes in proteins. This was the basic view from the 1950s until very recently.

As researchers became interested in how genes turn on and off and what factors influence this, it became apparent that the story was more complicated. It was discovered that the processes that determine which genes turn on and off could themselves be passed on to the next generation. Of course, which factors turn the genes on and off are largely influenced by the environment of the organism. Thus, although DNA itself could not be influenced by the environment, it was possible for the environment to influence future generations through its changes to those processes that turn genes on and off.

epigenetic inheritance: a form of inheritance by which factors largely influenced by the environment of the organism that turn the genes on and off can be passed on to the next generation without influencing DNA itself

This possibility of another form of inheritance came to be called epigenetic inheritance (Hallgrímsson & Hall, 2011; Nestler, 2011). Instead of actually changing the gene itself, epigenetic modifications mark a gene. This alters how it is turned on and off. Briefly, DNA is wrapped around clusters of proteins called histones. These are further bundled into structures called chromosomes. Being tightly packed keeps genes in an inactive state by preventing access to processes that turn genes on. When action is needed, a section of DNA unfurls and the gene turns on. Whether a segment is relaxed and able to be activated or condensed resulting in no action is influenced by epigenetic marks or tags (see Figure 2.26). As a tag, histone acetylation tends to promote gene activity and is called a writer. Histone methylation and DNA methylation tend to inhibit it and are called erasers.

In a classic study, rat pups raised by actively nurturing mothers versus more passive mothers differed in epigenetic factors.

Photo by Seweryn Olkowicz, Wikipedia

epigenetic marks or tags: factors that influence whether a gene segment is relaxed and able to be activated, or condensed, and thereby inhibited

The environment can influence these writer and eraser tags. Tags help an organism respond to a changing environment. Some tags last a short time, whereas others can last a lifetime. In a now classic study, researchers observed that some rat mothers displayed high levels of nurturing behavior, licking and grooming their pups, while others were less diligent (Weaver et al., 2004). Behaviorally, the offspring of the more active mothers were less anxious and produced less stress hormone when disturbed than pups cared for by more passive mothers. Further, the females raised by nurturing mothers became nurturing mothers themselves.

The intriguing part of this study was that the offspring of the rat mothers who showed more licking and grooming differed in epigenetic factors. Pups raised by passive mothers showed more DNA methylation than aggressively groomed pups in the regulatory sequences of a gene encoding the glucocorticoid receptor, which is a protein present in most cells in the body that mediates an animal’s response to the stress hormone cortisol. This excessive methylation was detected in the hippocampus, a brain region involved in learning and memory, and this causes nerve cells to make less of the receptor. Activation of the glucocorticoid receptor in the hippocampus actually signals the body to slow production of cortisol. The epigenetic reduction in receptor number exacerbated the stress response in the animals. This made the animals more anxious and fearful. Further, these traits persisted throughout their lifetime. Overall, attentive mothers cause the methyl marks to be removed. Inattentive mothers, on the other hand, cause methyl marks to be added. Thus, rats inherit certain behaviors based on experience. The genes had not changed, but the tags had.

Figure 2.26 Epigenetic Changes Alter Gene Activity

Source: Nestler (2011).

At this point, a variety of studies have shown other examples of epigenetic mechanisms at work. For example, the diet of a mouse mother before conception can influence the hair color of her infants and even her infants’ infants (e.g., Cropley, Suter, Beckman, & Martin, 2006). One interesting aspect of this research is the suggestion that a mother’s diet can influence future generations, independent of later changes in diet.

Fathers can also influence their offspring. It has been shown that a mouse will develop a diabetes-like disease if her father’s diet before her conception was high in fat (M. Skinner, 2010). Also, if a mouse father is overweight, then gene activity in the pancreas of his offspring will be abnormal (Ng et al., 2010). Since the pancreas makes insulin, which regulates blood sugar, this may set up the possibility of future diabetes. The opposite is also the case. If the father’s diet results in an underweight condition, then genes in the liver associated with fat and cholesterol synthesis were shown to be more active in their offspring (Carone et al., 2010). Another study suggested that whether a human father smoked early in life was associated with his sons being heavier in weight at age 9 (Pembrey et al., 2006).

Overall, this type of research implies that behavior and environmental experiences at critical periods could later influence characteristics for future generations. Current health research related to such disorders as diabetes and cancer, as well as types of psychopathology, is suggestive of such a relationship (see Katsnelson, 2010; van Os, 2010, for overviews). Both addiction and depression have been shown to have an epigenetic component (Nestler, 2011). Thus, epigenetic inheritance, which involves tags or marks that determine when genes are turned off or on, offers a parallel track to traditional Mendelian inheritance for influencing phenotypes. Further, a new area of research uses identical twins to study specific epigenetic mechanisms with the goal of determining how genetic and environmental factors influence epigenetics (e.g., Bell & Spector, 2011). This approach may offer better insight into the expression of complex traits as seen in normal and psychopathological processes.