Posted on Saturday, June 12, 2010
Much of both early and current thinking about the role of biological influences on disordered behavior implicates imbalances in body chemistry. Hippocrates speculated that adequate mental functioning relied on a proper balance of the four bodily humors: blood, phlegm, yellow bile, and black bile. Thus, for example, excessive black bile was thought to produce melancholia, or what we would today label depression.
While specific mechanisms for specific disorders are often questioned, there is fairly broad agreement that biochemistry in some form contributes to disturbed behavior. The biochemistry of neurotransmitters and central nervous system functioning have become important foci of biology's contribution to the study of behavior disorders.
The nervous system has billions of neurons, which conduct the electrochemical impulses by which communication occurs Neurons have three major parts: a cell body, dendrites which branch out from the cell body and can receive messages from other cells, and axons which transmit messages to other cells. These messages must cross the gap between neurons (the synaptic gap or cleft). When an impulse reaches the end of the-axon, neurotransmitters are released that cross the synaptic gap and communicate with another cell through receptor sites on that cell.
Neurotransmission can go awry in a number of ways. For example, too much or too little of a particular neurotransmitter can be released. Problems can also exist in reuptake--the process by which the neuron reabsorbs the neurotransmitter for subsequent transmissions. Also, the density and sensitivity of receptors to a particular neurotransmitter or the presence or absence of other chemicals, known as blocking agents, at the receptor sites can affect neurotransmission. A number of different neurotransmitters have been identified as playing a role in various forms of abnormal behavior such as depression and attention-deficit hyperactivity disorder (cf. Emslie et al., 1994; Pliszka et al., 1994). Norepinephrine, serotonin, dopamine, acetylcholine, and gamma amibutyric acid (GABA) are some of the major neurotransmitters that have been studied. The role of neurotransmitters is described in later chapters on various disorders.
How the biochemistry of the body, not only the brain, reacts to situations an individual may encounter is also part of the biological perspective on behavior disorders. The autonomic nervous system helps to regulate one's emotional state. It consists of two branches. The sympathetic nervous system mediates increased arousal, preparing the body for action. The parasympathetic nervous system, on the other hand, works to slow arousal and conserve the body's resources. One of the ways the autonomic nervous system operates is through stimulation of the endocrine system, a collection of glands that release hormones into the bloodstream. Research on neuroendocrine functioning is an important part of the study of a variety of child and adolescent disorders. For example, differences in autonomic reactivity in panic disorder, neurohormonal dysregulation in obsessive-compulsive disorder, and the role of growth hormone regulation in depression have received attention (cf. Dummit and Klein, i994; Emslie et al., 1994; Leonard et al., 1994). These and other biochemical influences will be discussed in later chapters.
The study of genetic influences on human behavior is extremely complex and cur-rently expanding in several directions (Lombroso, Pauls, and Leckman, 1994; Plomin, 1994a; Rutter et al., 1990a). Application to child and adolescent disorders is comparatively under-researched, but this is changing. Genetic research can tell us subtle things about etiology, for example, whether all or only some cases of a disorder are likely to have a genetic component. Genetic research can even confirm the role of environment in causation and point to characteristics of the environment that might be especially important (Plomin, 1994b).
A complete discussion of genetic influence on childhood disorders is not possible here. The topics selected for examination are intended to introduce this area and to facilitate understanding of later discussions of the genetics of specific behavior disorders.
Inheritance through single genes. Beginning with the work of Gregor Mendel, scientists have sought to describe inheritance of certain characteristics controlled by one gene pair. Mendel correctly hypothesized that each parent carries two hereditary factors (later called genes), but passes on only one to the offspring. He also noted that one form of the factor is dominant, in that its transmission by either parent leads to the display of that form of the characteristic. The other form, the recessive, displays itself only when it is transmitted by both parents. Both of these patterns, and the sex-linked pattern described below, are involved in the inheritance of many human attributes and disorders.
Huntington's chorea is an example of a disease transmitted by a dominant gene. This disease causes death, but does not show up until adulthood, when limb spasms, and mental deterioration and perhaps dementia become evident. Many people know of this inherited disease due to the death by it of Woody Guthrie, a well-known folk singer and father of Arlo Guthrie.
Tay-Sachs disease provides an example of a disorder carried by one gene pair and transmitted recessively. A degenerative disease of the nervous system, it usually results in progressive deterioration of mental abilities, motor capacities, and vision, and then death by the age of one to three. An estimated 60 to 90 percent of all cases of Tay Sachs is found among children of Ashkenazic Jewish heritage.
The sex-linked pattern of inheritance involves genes on the sex chromosomes. O special interest is the situation in which the relevant gene is recessive and carried on the X chromosome, such as in red-green color blindness, hemophilia, and Lesch-Nyhan Syndrome. The latter is a rare, untreatable disorder that results in unusual motor development, mental retardation, and extreme self -mutilation in children. The disorder is found only in males, who die early and thus do not have offspring. The Lesch Nyhan child has a normal father and a mother who carries the disorder, having one normal X chromosome and one affected X chromosome. Sons receive their only X chromosome from their mothers. Those who receive the recessive defective gene will develop the disorder, since the Y chromosome transmitted from the father carries no gene at all to offset the defective gene. Daughters receive one X chromosome from each parent. If a girl receives the defective recessive gene from her mother, it is usually offset by the dominant normal gene from her father; she has no affliction herself but could transmit Lesch-Nyhan to her son.
Researchers continue to explore the effects of single gene pairs or other relatively simple genetic etiology on specific behavior disorders. Such research has been facilitated by new genetic methods (cf. Lombroso et al., 1994). Segregation analysis uses statistical procedures to examine the pattern of disorder as well as genetic makeup within a family and compare it to a specific genetic model of inheritance, such as a dominant or recessive gene model. The results allow inferences about the pattern of genetic inheritance for a disorder. Linkage analysis explores whether the pattern in which a specific disorder appears among family members is the same as for genetic markers. The approximate chromosome location is known for the genetic markers. For example, inherited disorders, such as color blindness, that are known to be linked to a particular chromosome have been used as markers. If the behavior disorder and color blindness appear in family members in the same pattern then it can be presumed that the genes that control them are close neighbors on the same chromosome. Advances in molecular genetics have also identified a large group of DNA fragments (called restriction fragment length polymorphisms and variable tandem repeats) for which chromosomal location is known. These fragments can serve as genetic markers for linkage analysis in the same way as indicted for color blindness.
The efforts of Nancy Wexler and a team of research scientists in searching for the gene responsible for Huntington's disease is an example of recent advances. Through the use of linkage analysis techniques the disorder had been mapped to an area on chromosome 4 and recently Wexler's group was able to identify the gene responsible for Huntington's disease (Huntington's Disease Collaborative Research Group, 1993).
Investigating the effects of multiple genes. In contrast to the effects due to a single gene pair, most of the behaviors we are concerned with in studying child and adolescent behavior disorders are thought to involve many genes as well as environmental influences. Such multifactorial inheritance is much more difficult to trace than single gene effects. Accordingly, the study of genetic influences on human behavior relies on a combination of evidence from a variety of research methods. We will now look briefly at the major research methods of behavior genetics.
Youth with behavior disorders often have parents, siblings, and other family members with similar problems. However, such aggregation of behavior problems in families does not mean a genetic influence is operating. Family environment may also be operating. One of the goals of research is thus to determine the degree of genetic influence operating in specific behavior disorders.
The three major research strategies of behavior genetics that have been applied to, behavior disorders are the twin, family, and adoption methodologies (Plomin, 1994b). These methods are employed to assess heritability, a statistic that indicates the degree to which genetic influence accounts for variance in behavior among individuals in the population studied. Importantly, the contribution of environmental influences is also obtained.
The essence of twin designs is a comparison of identical twin resemblance (concordance) to fraternal twin resemblance. Identical or monozygotic (MZ) twins have identical genes. Fraternal or dizygotic (DZ) twins are on average only 50 percent alike genetically; in fact, they are no more alike genetically than any two siblings. In its most basic form, the twin method points to genetic influence if there is greater concordance among identical twins than among fraternal twins. That is, genetic influence is suggested when a disorder occurs more frequently in both members of MZ twin pairs than it does in both members of DZ twin pairs (cf. Edelbrock et al., 1995).
Family studies expand upon the logic of twin studies. The relatives of an individual identified as exhibiting a certain behavior or disorder (the proband) can be examined to determine whether or not the relatives exhibit the same behavior or problem. Identical twins are 100 percent genetically related. First-degree relatives' (parents and their offspring and siblings) average genetic relatedness is 50 percent. Half-siblings and other second-degree relatives are 25 percent genetically related. Third-degree relatives, such as cousins, are only 12.5 percent genetically related. If there is a genetic influence on a disorder, family members who are genetically more similar to the proband should be more likely to exhibit the same or related difficulties. Statistical estimates of heritability are possible.
Adoption studies are designed to evaluate the relative contributions of genetics and environment by studying adopted and non adopted individuals and their families. One strategy is to start with adopted children who display a particular behavior disorder and to examine rates of that disorder in members of the children's biological families compared to rates in their adoptive families. Another strategy is to start with biological parents who exhibit a particular disorder and examine the rate of disorder in offspring separated from the parent in early childhood and raised in another household. Rates of disorder in these children can then be compared to a number of comparison groups (e.g., siblings not given for adoption and raised by the biological parent). Also associations between risk factors, such as family conflict, and behavior problems can be compared in adopted and non adopted youngsters. Adoption strategies can thus help reveal complex relations between genetic and environmental influences (cf. Braungart-Rieker et al., 1995).
All behavior genetic methods have limitations and potential confounds. For example, in adoption studies, prenatal as well as genetic factors are pan of the biological parent's "contribution." Thus, greater rates of disorder among biological relatives than adoptive relatives could be due to prenatal influences. Combinations and refinement of methods, and more sophisticated quantitative analyses, seek to address many of the shortcomings of individual methods. These advances also permit evaluation of hypothetical models of genetic transmission and of the interaction of genetic and environmental influences (Plomin, 1995; Plomin, DeFries, and McClearn, 1990; Rutter et al., 1990a).
Results from behavior genetic research suggest that heritability estimates for behavioral dimensions or disorders. rarely exceed 50 percent, and that heritability is often appreciably lower than this (Plomin, 1994b). This means that substantial variation in behavior is attributable to non genetic influences. In this way behavior genetic research has provided evidence for the importance of environmental influence. Influences of family environment that are shared by siblings and that contribute to their development can be revealed. Behavior genetic research has also highlighted the importance of environmental influences that are not shared by children growing up in the same family. These influences, known as non shared environment, make children in the same family different from one another. They are also important to the development of behavior disorders (Hetherington, Reiss, and Plomin, 1994; Plomin, Chipuer, and Neiderhiser, 1994).
Chromosome abnormalities. Approximately 40 percent of spontaneously aborted fetuses are known to have chromosomal abnormalities. Among live births it has been estimated that 3.52 infants per 1,000 are born with an abnormal number of chromosomes and 2.23 with structural abnormalities of the chromosomes (Gath, 1985).
Chromosomes that are aberrant in either number or structure are known to cause death or a variety of deficiencies. These "accidents" are often not inherited, so that they influence only the specific developing embryo. A large number of different chromosomal anomalies have been described. Mental retardation is commonly associated with many of them. Perhaps the most widely recognized disorder attributed to a chromosome aberration is Down's syndrome. Characterized by mental deficiency, it is usually caused by an extra #21 chromosome. A group of abnormalities that results from sex chromosome aberrations has also been discovered. These disorders are often characterized by below-average intelligence, atypical sexual development, and other difficulties.
Newer methods of chromosomal analysis, such as staining methods, allow detection of quite subtle abnormalities in size, shape, and other characteristics of portions of chromosomes. Also, the discovery of a group of structural features known as fragile sites has proven helpful in understanding the origins of certain disorders. For example, the fragile X anomaly is due to a fragile site on the X chromosome. This condition is thought to be responsible for many cases of severe mental retardation (Lombroso et al., 1994; Rutter et al., 1990a).
Category Article Behavior Disorder