The transmission of information throughout the nervous system takes place at synapses, or points of communication between neurons. Electrical signals containing information transmit chemically across the synapse from one neuron to the next. Through this transmission, neurons form complex pathways along which information travels from one part of the nervous system to another. Neurotransmitters are the chemical messengers that travel across the synapse, allowing neurons to communicate with their neighbors. Table 4.1 shows the proposed role of several major neurotransmitters in psychological disorders.
Apart from disturbances in neurotransmitters, abnormalities in the brain structures themselves can also cause psychological symptoms. Although it’s not always possible to link brain structures that are too large or too small to behavioral impairments, researchers believe that some disturbances in behavior have a connection to abnormally developed or functioning brain structures. Because we cannot directly observe brain structures, researchers have developed sophisticated brain scanning methods to allow them to measure how an individual’s brain is structured and, more importantly, how it performs while it is processing information.
The causes of nervous system dysfunction range from genetic abnormalities to brain damage. Genetic abnormalities can come about through the inheritance of particular combinations of genes, to faulty copying when cells reproduce, or to mutations that a person acquires over the course of life. Cells do possess the ability to repair many of these mutations. If these repair mechanisms fail, however, the mutation can pass along to the altered cell’s future copies.
Genes contain the instructions for forming proteins, which, in turn, determine how the cell performs. In the case of neurons, genes control the manufacturing of neurotransmitters, as well as the way the neurotransmitters behave in the synapse. Genes also determine, in part, how the brain’s structures develop throughout life. Any factor that can alter the genetic code can also alter how these structures perform.
Inherited disorders come about when the genes from each parent combine in such a way that the ordinary functioning of a cell is compromised. Your genotype is your genetic makeup, which contains the form of each gene that you inherit, called an allele. Let’s say that Allele A causes a protein to form that leads a neuron to form abnormally. Allele B causes the neuron to be entirely healthy. If you have inherited two genes containing Allele B, then you have no chance of developing that disease. If, on the other hand, you have inherited two genes containing Allele A, you will almost certainly get the disease. If you inherit one Allele A and one Allele B, the situation becomes more complicated. Whether or not you get the disease depends on whether Allele A is “dominant,” meaning that its instructions to code the harmful protein will almost certainly prevail over those of Allele B. If Allele A is “recessive,” then it alone cannot cause the harmful protein to form. However, because you are an AB combination, you are a carrier because should you produce a child with another AB carrier, that child could receive the two AAs, and therefore develop the disorder (Figure 4.1).
The dominant-recessive gene inheritance model rarely, if at all, can account for the genetic inheritance of psychological disorders. In some cases, inherited disorders come about through maternal linkages only, meaning that they transmit only through the mother. These disorders occur with defects in the mitochondrial DNA, which is the DNA that controls protein formation in the cell’s mitrochondria (energy-producing structures). Many psychological disorders reflect a polygenic model involving the joint impact of multiple gene combinations.
To complicate matters further, not only are multiple genes involved in the development of psychological disorders, but the environment plays an important role in contributing to the way our behavior reflects our genetic inheritance. Your phenotype is the observed and measurable characteristic that results from the combination of environmental and genetic influences. Some phenotypes are relatively close to their genotype. For example, your eye color does not reflect environmental influences. Complex organs such as the brain, however, often show a wide disparity between the genotype and phenotype because the environment to which people are exposed heavily influences brain development throughout life. Moreover, there are numerous genes that participate in building the structures in the brain and influencing their changes over time. The study of epigenetics attempts to identify the ways that the environment influences genes to produce phenotypes.
Reflecting the complexity of the brain’s structures and functions, leading researchers in schizophrenia (Gottesman & Shields, 1972; Gottesman & Shields, 1973) proposed the use of the term “endophenotypes” to characterize the combination of genetic and environmental contributors to complex behaviors. An endophenotype is an internal phenotype, that is, a characteristic that is not outwardly observable. In the case of schizophrenia, for example, there are several possible endophenotypes that may underlie the disease’s outwardly observed symptoms. These include abnormalities in memory, sensory processes, and particular types of nervous system cells. The assumption is that these unobservable characteristics, which heredity and the environment influence, are responsible for the disease’s behavioral expressions. The concept of endophenotypes was probably decades ahead of its time, because in the 1970s, researchers were limited in what they could study both in terms of genetics and the brain. With the development of sophisticated DNA testing and brain imaging methods, the concept is seeing a resurgence (Gottesman & Gould, 2003).
The relationships between genetic and environmental influences fall into two categories: gene-environment correlations and interactions between genes and the environment (Lau & Eley, 2010). Gene-environment correlations exist when people with a certain genetic predisposition are distributed unequally in particular environments (Scarr & McCartney, 1983). These correlations can come about in three ways. The first way is through passive exposure. Children with certain genetic predispositions can be exposed to environments that their parents create based on their genetic predispositions. For example, a child of two athletically gifted parents who participate in sports inherits genes that give this child athletic prowess. Because the parents themselves are involved in athletic activities, they have created an environment that fosters the child’s own athletic development. This elicits the second gene-environment interaction and can occur when the parents treat the children with certain genetic predispositions in particular ways because their abilities bring out particular responses. Returning to our example, the school coach may recruit the athletically gifted child for sports teams starting in early life, leading the child to become even more athletically talented. We call the third geneenvironment correlation “niche picking.” The athletically gifted child may not wait for recruitment, but instead seeks out opportunities to play sports, and in this process becomes even more talented. In terms of the development of psychological disorders, any three of these situations can occur, heightening the risk that children of parents with genetic predispositions are more likely to develop the disorder because of the environment’s enhancing effect.
Gene-environment interactions occur when one factor influences the expression of the other. In the case of people with major depressive disorder, for example, researchers have found that people with high genetic risk are more likely to show depressive symptoms when placed under high stress than are people with low genetic risk. Thus, the same stress has different effects on people with different genetic predispositions. Conversely, the genetic risk of people exposed to higher stress levels becomes higher than that of people who live in low-stress environments. In other words, a person may have a latent genetic predisposition or vulnerability that only manifests itself when that individual comes under environmental stress. In these studies, the researchers defined genetic risk in terms of whether or not an individual had a close relative with disorder symptoms. The genetic risk presence did not predict whether or not the person developed major depressive disorder unless that individual was exposed to a high-stress environment (Lau & Eley, 2010).
Researchers studying psychopathology have long been aware of the joint contributions of genes and the environment to the development of psychological disorders. The diathesis-stress model proposed that people are born with a diathesis (genetic predisposition) or acquire vulnerability early in life due to formative events such as traumas, diseases, birth complications, or harsh family environments (Zubin & Spring, 1977). This vulnerability then places these individuals at risk for the development of a psychological disorder as they grow older (Johnson, Cohen, Kasen, Smailes, & Brook, 2001).
With advances in genetic science, researchers are now much better able to understand the precise ways in which genes and environmental factors interact. Usually, people inherit two copies of a gene, one from each parent, and both copies actively shape the individual’s development. However, certain genes regulate through a process known as epigenesis, meaning that the environment causes them to turn “off ” or “on.” If the remaining working gene is deleted or severely mutated, then a person can develop an illness. The process of DNA methylation can turn off a gene as a chemical group, methyl, attaches itself to the gene (Figure 4.2) (http://www.nature.com/scitable/topicpage/ the-role-of-methylation-in-gene-expression-1070).
Through the epigenetic processes of DNA methylation, maternal care, for example, can change gene expression. One study showed that during pregnancy, a mother’s exposure to environmental toxins caused DNA methylation in her unborn child (Furness, Dekker, & Roberts, 2011). Studies on laboratory animals also show that stress can affect DNA in specific ways that alter brain development (Mychasiuk, Ilnytskyy, Kovalchuk, Kolb, & Gibb, 2011). Researchers believe that certain drugs that the mother uses during pregnancy cause DNA methylation, including nicotine, alcohol, and cocaine.
To understand the contributions of genetics to psychological disorders, researchers use three methods: family inheritance studies, DNA linkage studies, and genomics combined with brain scan technology. In family inheritance studies, researchers compare the disorder rates across relatives who have varying degrees of genetic relatedness. These studies examine disorder rates in different pairs of genetically related individuals. The highest degree of genetic relatedness is between identical or monozygotic (MZ) twins, who share 100 percent of their genotype. Dizygotic (DZ) or fraternal twins share, on the average, 50 percent of their genomes, but both types of twins share the same familial environment. Therefore, although MZ-DZ twin comparisons are useful, they do not allow researchers to rule out the impact of the environment. Similarly, studies of parents and children are confounded by the fact that the parents create the environment in which their children are raised. In order to separate the potential impact of the environment in studies comparing MZ and DZ twins, researchers turned long ago to adoption studies in which different families raised MZ twins, and therefore the twins experienced diff erent environments.
For decades, family and twin studies were the only methods researchers had at their disposal to quantify the extent of genetic influences on psychological disorders. With the advent of genetic testing, however, researchers became able to examine specific genetic contributions to a variety of traits, including both physical and psychological disorders.
In a genome-wide linkage study, researchers study the families of people with specific psychological traits disorders. The principle behind a linkage study is that characteristics near to each other on a particular gene are more likely inherited together. With refined genetic testing methods available, researchers can now carry this task out with far greater precision than was true in the past.
Although useful, linkage studies have limitations primarily because they require the study of large numbers of family members and may produce only limited findings. In genome-wide association studies (GWAS), researchers scan the entire genome of individuals who are not related to find the associated genetic variations with a particular disease. They are looking for a single nucleotide polymorphism (SNP) (pronounced “snip”), which is a small genetic variation that can occur in a person’s DNA sequence. Four nucleotide letters—adenine, guanine, thymine, and cytosine (A, G, T, C)—specify the genetic code. A SNP variation occurs when a single nucleotide, such as an A, replaces one of the other three. For example, a SNP is the alteration of the DNA segment AAGGTTA to ATGGTTA, in which a “T” replaces the second “A” in the first snippet (Figure 4.3). With high-tech genetic testing methods now more readily available, researchers are much better able to find SNPs that occur with particular traits (or diseases) across large numbers of people. Although many SNPs do not produce physical changes in people, researchers believe that other SNPs may predispose people to disease and even influence their response to drug regimens.
Imaging genomics increasingly augment genetic studies. Researchers can combine linkage or association methods with imaging tools to examine connections between gene variants and activation patterns in the brain.