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Abnormal Psychology. William J. Ray
Читать онлайн.Название Abnormal Psychology
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isbn 9781506333373
Автор произведения William J. Ray
Издательство Ingram
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.
Mitochondria and Mitochondrial Inheritance
Mitochondria are structures within a cell that are involved in the production of energy. It is assumed that mitochondria descended from bacteria that began to live inside single-celled organisms more than a billion years ago. As such, mitochondria have their own DNA (see next paragraph), which contains 13 coding genes with about 16,000 base pairs. Thus, a given cell in your body contains both the nuclear DNA and mitochondria and their DNA.
What is interesting is that generally mitochondrial DNA (mtDNA) is inherited only from the mother, clearly a violation of Mendelian inheritance. Because mtDNA does not recombine sections of DNA from the mother and father, it is very stable and mutates slowly. This gives mtDNA a special application in the study of evolution. It has helped researchers to discover the genetic link in certain disorders that show maternal or mitochondrial inheritance patterns, such as Leber’s hereditary optic neuropathy, a disorder that results in rapid loss of vision beginning in adolescence.
mitochondrial DNA (mtDNA): deoxyribonucleic acid (DNA) of mitochondria structures within a cell; because mtDNA does not recombine sections of DNA from the mother and father, it is very stable and mutates slowly
mitochondrial inheritance: generally mitochondrial DNA (mtDNA) is inherited only from the mother. mtDNA is contained within each cell and is related to energy production
Evidence is also accumulating that mitochondrial dysfunction is involved in specific mental disorders (Regenold et al., 2009; Rossignol & Frye, 2012). This is referred to as the mitochondrial dysfunction hypothesis. Mitochondrial dysfunction has been identified using a number of different techniques. One technique is to identify structural changes in mitochondria. A second is to examine the manner in which the mitochondrially related genes produce proteins. A third is the use of metabolic studies. Since mitochondria are involved with energy production, it is possible to measure glucose concentration in cerebrospinal fluid. These studies have shown differences in mitochondrial functioning in individuals with bipolar disorder, schizophrenia, and autism spectrum disorders as compared to healthy controls.
What Are Endophenotypes?
In a move to go beyond using only the signs and symptoms of psychopathology, there has been a search for stable internal physiological or psychological markers that underlie a disorder (Gottesman & Hanson, 2005; Gottesman & Shields, 1972; Insel & Cuthbert, 2009; G. Miller & Rockstroh, 2013). Such markers have been called endophenotypes. Endophenotypes are patterns of processes that lie between the gene (the genotype) and the manifestations of the gene in the external environment (the phenotype). Unlike symptoms that can be observed, endophenotypes cannot be seen except with special equipment and computational