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 analysis such as brain imaging procedures or patterns of performance on neuropsychological tests. For example, individuals with a given disorder may show certain types of electroencephalogram (EEG) responses to particular stimuli or a certain pattern of brain activity that is different from that seen in healthy individuals. Those with autism have been shown to have fewer connections between brain areas than siblings or controls, and this is seen as an endophenotype (Moseley et al., 2015).
endophenotypes: patterns of processes that lie between the gene (the genotype) and the manifestations of the gene in the external environment (the phenotype)
Like genes, the presence of the endophenotype does not necessarily mean that the disorder itself will be present. For example, a specific endophenotype may be seen in both a person with schizophrenia and his or her first-degree relatives, although the relatives themselves do not have schizophrenia. As such, an endophenotype can help to identify the systems involved in a particular disorder as well as note which genes are influenced by environmental and other internal factors related to a disorder. The potential of endophenotypes is their ability to better articulate the relationship between genetic and environmental factors in the development of psychopathology and to clarify which processes are influenced. In Chapter 4, you will learn about a National Institute of Mental Health (NIMH)–supported diagnostic approach based on endophenotypes, the Research Domain Criteria (RDoC).
Concept Check
What are the two important principles of Mendelian genetics? What evidence led Mendel to their discovery?
What do genes do, and how and where do they do it? What are the roles of DNA and RNA in that process?
How do we know that genes change behavior? What kinds of research have been done with animals to identify the specific genes involved?
What is epigenetic inheritance? How does it work?
What is an endophenotype, and how does it relate to psychopathology?
Evolution and Psychopathology
Thus far, we have considered brain changes and genes turning off and on. These events are typically short term and can change quickly. Moving to the evolutionary perspective, we will look at a longer time frame in which environmental factors influence the genes that are passed on to the next generation. Let’s begin with the major themes of evolution and then consider psychopathology from an evolutionary perspective.
The Themes of Evolution
One of the main themes of evolution is the manner in which organisms are in close connection with their environment. It is this close connection that allows for change to take place, including the turning on and off of genetic processes. In humans, there is another layer of complexity involved in the process. Part of this complexity comes from the fact that humans are born less fully developed at birth than many other species and thus are sensitive to changes in their environment as they continue to develop. This includes our
