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Genetic Factors In Larger And Morecomplex Segments Of Behavior - Factors In Behavior

twins schizophrenia identical traits environmental psychiatric degree incidence evidence conditions

A problem most relevant to psychiatry and medicine, in general, is the direct inheritability of complex segments of behavior such as personality traits. That both intelligence and temperamental qualities are inheritable to some extent is well known to breeders of domesticated animals. In fact, knowledge of this has made it possible to breed dogs and other mammals for specific qualities which have been put to various uses, for example, German shepherds for lead dogs for the blind and Collies for the herding of sheep. Even here, however, it may be argued that physical traits are actually being selectively bred which favor the development of one or another psychologic trait.

A classical experimental study of the inheritability of psychologic traits is that of Tryon (20). He demonstrated, by selective breeding, that maze-learning ability is inheritable in the rat. Those rats who scored highest, making the most errors in running a T - maze with 17 blinds, were mated together and those making the fewest errors mated together. After 7 generations of breeding there was practically no overlap in the performance of the maze-bright and the maze-dull progeny.

Breeding experiments have provided evidence for the inheritability of other traits as well. Among these are emotionality (8), as measured by the frequency of defecation and urination of the rat in a strange situation, and hoarding behavior (18). The role of genetic factors in the behavior of rats is vividly illustrated by differences seen in different strains. For example, gray Norway rats show much greater emotionality than Wistar albino rats (5). The difference is seen even when the animals are raised from birth under exactly the same environmental conditions.

Identification of the role of genetic factors in complex human behavior is particularly difficult. This is due in part to the ease with which human behavior is modified by the physical and social environment and the practical impossibility of conducting breeding experiments. Nevertheless, there is good reason to believe that genetic factors do contribute to differences in normal personality characteristics as well as to frank psychiatric disorder. Since the role of genetic factors can be identified in the recent phylogenetic history of man (e.g., higher mammals), it is reasonable to assume they play a role in humans also. The observation that high intelligence and many special traits, such as musical talent, tend to run in families supports this view. Also, there is evidence that much of the physical substrate of man, of which psychologic activity is a product, has strong genetic determinants. The inheritability of gross physical traits has already been mentioned. On the level of the autonomic nervous system, Jost and Sontag (9) have reported interesting data from a study conducted over a three-year period involving 217 children of the ages 6 to 12 years. They found that the degree of similarity of autonomic responses, such as pulse pressure, skin resistance, and vaso-motor persistence, varied directly with the degree of consanguinity (genetic relatedness). Another example of this is the finding of similar EEG abnormalities in relatives. This suggests genetic factors in brain structure and function.

Genetic Factors In Psychiatricdisorders

Early studies of the genetics of human illness relied heavily on pedigree data. Detailed family histories were obtained from individuals with a particular disease. The finding of a higher incidence in related individuals than in the general population is suggestive of hereditary factors, particularly if there is a correlation between the incidence or risk of the disease in question and the degree of consanguinity of those afflicted. However, related individuals tend to. have similar environments which make inferences of a genetic nature from such data hazardous. Reliance on inaccurate or incomplete medical records or the inaccurate recollections of untrained observers are added problems. Such pedigree studies are only conclusive in diseases with a high familial incidence and diseases in which environmental modification is relatively slight. An example is Huntington's chorea, a disease characterized by involuntary movements and progressive mental deterioration, which is inherited as a Mendelian dominant.

Nevertheless, some clues can be obtained in mental illnesses with less clear hereditary factors by taking large numbers of family histories. The risks of relatives of varying degrees of kinship of manifesting the disease in question can be estimated statistically. Such statistical data also provide clues as to the importance and modus operandi of genetic factors in the illness.

The family history method of genetic analysis becomes more meaningful in some special situations, as in isolated communities with a high degree of inbreeding. The high consanguinity rate in marriage in such communities favors the appearance of homozygotes, and hence, a higher incidence of recessive defects. For example, Book (2) studied the incidence of schizophrenic illness in three isolated parishes in the north of Sweden. He reported that most of the affected cases could be traced to 31 ancestoral pairs constituting one family pedigree. On the basis of these data Book postulated a dominant gene in schizophrenia with reduced manifestations depending in part on environmental factors and the possible operation of other genetic factors.

Perhaps the best source of evidence about the genetics of human psychiatric illness is provided by co-twin studies. Identical (monozygotic) twins have identical genetic make-up, being derived from the fission of the embryo early in development. On the other hand, fraternal (dizygotic) twins result from the simultaneous fertilization of two ova and are no more related genetically than ordinary siblings. Thus, a higher concordance rate of a characteristic in identical twins over that of fraternal twins is assumed to reflect the role of genetic factors. This assumes, of course, that the social and personal environments of identical twins are no more similar, traumatic, or otherwise different than that of fraternal twins. However, it may be argued that the closer similarity of identical twins generates special stresses which might influence the risk of some illnesses, especially those of a psychologic nature. For this reason, comparisons have been made in the concordance rate of psychiatric disturbances in identical twins reared apart and those reared together. Differences here are assumed to reflect this environmental difference. Thus, comparisons of concordance rates between identical twins and fraternal twins, reared apart and together, as well as the incidence in ordinary siblings and persons of differing degrees of relatedness, provide information about the degree and nature of genetic factors in psychiatric conditions. Kallmann (10) has made particular use of this method in studying the genetics of schizophrenia and other psychiatric disorders. Table 1 shows such data collected in a large number of cases with respect to schizophrenia. Note that the concordance rate of schizophrenia varies with the degree of consanguinity. However, note also that the incidence is higher with identical twins reared together than those reared apart. This highlights the interaction of genetic and environmental factors. Similar evidence, although less clear-cut and involving fewer cases, has been collected by Kallmann which indicates a genetic factor in other psychiatric conditions, such as manic-depressive psychosis and homosexuality (11).

In summary, it does appear that genetic factors are of importance in many psychologic traits and disorders of behavior. This does not imply, however, that other etiologic factors, some of which will be treated later in the text, are not important also. Evidence of etiologic factors of a biochemical, neural, and environmental nature in many psychiatric conditions is increasing. It is likely that in those conditions for which strong genetic evidence exists, such as schizophrenia, environmental conditions greatly determine the onset, manifestations, and course of the illness.

DIZYGOTIC MONOZYGOTIC TWINS Numbers are percentages of persons with stated degree of relatedness to a known case of schizophrenia who were found also to have schizophrenia. (Adapted from Kallmann, F. J. The genetic theory of schizophrenia, Am. J. Psychiat., 103:307, 1946.)

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