GENETIC BASIS OF HUMAN BEHAVIOR

Folia Psychiatrica et Neurologica Japonica, Vol. 18, No. 3, 1964

GENETIC BASIS OF HUMAN BEHAVIOR*

BY

Eiji INOUYE, M.D., D. Med. Sc.

Professor of Psychiatry and Human Genetics Znstitute of Brain Research

University of Tokyo School o f Medicine Tokyo, Japan

INTRODUCTION

The present situation of human behavior genetics is a matter of controversy. The reasons are firstly that there are many factors determining the behavior patterns of human individuals. Secondly there are interactions among the factors, and finally an approach to a factor from a discipline often draws a conclusion which is hardly acceptable by another discipline. By routine methodology of a discipline like genetics, psychiatry and psychology, no conclusive evidence on the genetic basis of human behavior has been easily obtained. In other words human behavior genetics is still in its premature stage of development in terms of methodology, despite a relatively long history since the pioneer work by Sir Francis Galton4) in 1875. Taking a few examples, routine pedigree studies on several types of neurotic reaction revealed an exceeding number of neurotics and other abnormal persons among the relatives of the propositi than among the control family members (McTnnesls), Brown')). These findings suggest the possible hereditary predisposition of the disorder. However, there is another interpretation of the finding emphasizing that the neurosis of the propositi would be the product of an unfavourable psychological and social environment in which those neurotics and abnormal persons were involved. I n another example even the high concordant rate of schizophrenia in monozygotic twins is seen from a psychoanalytic point of view as a result of a particular emotional relationship between two members of a pair (Jackson1*)). In an example of the opposite extreme the patients having been diagnosed as schizophrenia were the subjects of forced sterilization under a fascist legislation. This misuse of eugenics in turn caused an antagonism to the science of human genetics. These examples indicate that diverse conclusions can be drawn by different disciplines from a single finding, and it is particularly true if the interpretation of data is made with a prejudice. This article intends, therefore, to provide problems rather than to give a decisive conclusion.

Before discussing the findings in our study, a review on the positive findings

* Dedicated to late Professor Emeritus Tsunetaro Fujita. Presented at the US.-Japan Joint Seminar on the Neurological Basis of Behavior at Center for East-West Studies, Honolulu, Hawaii, U.S.A. on May 2nd, 1964.

Received for publication June 2, 1964.

184 E. Inouye

with respect to the genetic basis of human behavior will be stated briefly.*

SOME POSITWE FINDINGS

Even the behavioral scientists who are most antagonistic towards the concept OE the genetic basis of human behavior have begun to agree, I believe, the significance of the genetic basis in some instances of hereditary metabolic disorders which result in diseases of the central nervous system under usual circumstances. Phenyl- ketonuria is a classical example (Jervis13)), and a number of disorders of this category of different genetic loci and different biochemical properties is being found (Hsia?)). Although the progress in this field of research is rather slow, an approach to a large group of heredodegenerative neurological diseases may, sooner or later, reveal the specific metabolic errors in these diseases. From the standpoint of behavioral science, however, there still exists a considerable deficiency of knowledge on the process of development of a particular behavior of the psychological level having started from a mutant gene through the levels of biochemistry, morphology and so forth.

Chromosomal aberrations manifesting mental deficiency are not exceptional cases with the above-mentioned respect. Nevertheless, these two categories of pathological conditions provide clearest evidence of the genetic basis of intellectual disturbances.

The third category of the subjects of research comes from systematically conducted pedigree and twin studies on mental disorders which manifest disturbances of emotion, intelligence and drive. Statistical studies on the risk of being affected by one of the two major psychoses in family members revealed that the closer the kinship the greater the risk of one of the psychoses (L~xenburge r l~ ) , Kal1mannl4)). Idiopathic epilepsy (Lennox et al.la)), atypic psychosis ( Mitsudalg)), mental deficiency of unknown origin (Hayash# ) and several types of psychopathic personality (Panse*l)) and neurosis showed familial occurrences. The most reliable technique in this field of research is the twin study method, because monozygotic co-twins, and also partners of monozygotic triplets etc., are the only available genetic duplicates of human individuals. By the observation of these control subjects we learn another possibility of physical and psychic development having started from a given genotype and being modified by many factors. By means of the technique the above mental disorders were indicated to show a higher concordant rate in monozygotic twins than in dizygotic twins. Even ni the superficially dissimilar monozygotic co-twins we could frequently observe probable basic disturbances of the disorder ( Inouyelo-") 1 . Nevertheless, as stated before, contribution of a gene or genes to these pathological conditions is still subject to controversy. I think this is mainly due to traditional and naive dichotomie, heredity vs. environment.

Aside from studies on these pathological conditions there is another topic. It is the resemblance of psychological test scores among family members. Intelligence tests are the most favourite subjects, and it has been indicated repeatedly that at least in a civilized society the IQ is critically influenced by the genotype (TakumaZ4)). At the same time the presence of monozygotic twins with invariably diverse scores shows

* The citation of literatures was limited to a minimal number in order to give a brief review on the evidences of the genetic basis under discussion.

Genetic Basis of Human Behavior 185

the significance of prenatal and paranatal nonspecific hazards to intellectual development ( T a k ~ m a ~ ~ ) ) . These hazards are usually not detectable by the routine medical examination of individual subjects. A more attractive topic in this field of research is the intra-familial resemblance of various personality test scores. It has been shown in a large number of personality tests and subtests, that monozygotic twins resemble each other more than dizygotic twins (Vandenberg26)). Heritability* of these scores is slightly or exceedingly over zero. This means that there is more or less a contribution of the genotype to the scores. However, interpretation and integra- tion of these figures of heritability are not easy, and most studies do not advance beyond merely providing an array of figures. In these studies we are still far from unconvering an underlying mechanism determining individual behavior patterns. Factor analysis and multiple variance analysis (Catte12), Cattel et al.3)) are the next step, but there are fundamental and serious problems such as, what do the factors really mean, and will the results be confirmed in the studies employing other test batteries or in the studies carried out on the subjects in different cultural and ethnic groups.

OBSERVATION OF ACTUAL BEHAVIOR OF TWINS

Another field of research is the studies based upon collected informations on the life histories of selected subjects, or studies based upon observations of actual behavior of these subjects. Among the numerous references I particularly cite the name of a German author, Kurt Got t~chald t~) . While other German researchers of the pre-war period seem to have been too much occupied with philosophic or metaphysic “Charakterologie” or the theory on character, Gottschaldt, who is a scholar of Lewin’s school of psychology and who now lives in West Germany, conducted a series of pioneer studies in which investigators lived together with twin subjects. He observed actual behavior of the subjects under everyday situations as well as experimentally constructed situations. At the University of Tokyo a series of studies using a similar methodology was started in 1941 (Okada20), Suwa22), Uchi- mura et al.25)). Starting in 1948 a new tool of study was added. Every year around twenty pairs of twins of the age of 12 are admitted to the Highschool attached to the University. They are available for six years’ longitudinal observation and examination. Various kinds of data, which are still unsatisfactory, have been thus accumulated.

If the behavior of healthy monozygotic twins of preadult age was evaluated from a psychiatric point of view, it was nearly without exception indicated that they show a marked similarity in their activity and, to a lesser degree in their temperament than dizygotic twins. The significance of possibly heritable activity and temperament was also indicated in the study of monozygotic twin pairs, a part of whom experienced different psychological and social environmen!s because of adoption of a member of each pair in their infancy (Inouye8)).

* Heritability in twin data is usually defined as rmr-rdr, where rmz represents the

intra-class correlation coefficient in monozygotic twins, while rdr represents that in same- sexed dizygotic twins.

l -u r

I86 E. Inouye

HERITABILITY OF SPONTANEOUS ACTIVITY AND SENSE OF ELAPSED TIME

The next step of our study was the trial to reproduce these seemingly heritable personality traits in the score of measureable behavior. The following experiments were selected for discussion from among many trials, since in these experiments it was felt that we were likely to be able to reveal the heritable behavioral traits.

The first experiment was conducted by TakagW on four male and four female monozygotic twin pairs of the ages of 11 to 14, including five pairs in which a twin was adopted. The experiment was designed to test the level of aspiration, and there were five tests from A to E of different degrees of difficulty. The materials were comic strips! which were cut into two pieces, three pieces and so on. The subjects were asked to place the separated frames of each strip in an order to make a story and to tell the story after the arrangement of a strip had been concluded. Twin members of a pair were examined separately. This diagram The result is shown in Figure I .

a Time of Petormanee

0 Time of Telling Story

A,B. . . Test Number

. ) M F M F F M

TWIN S U B J E C T S

F M

Fig. 1. Unconscious Performance Time of Monozygotic Twins (Takagi, 1956)


indicates the order of their performance on test A, B and so on and the time required for each arrangement and for the telling of the story. As shown in the diagram the order of the performance and time spent for each task vary widely between two members of a pair. The total performance time varied between 8 minutes 30 seconds and 19 minutes, but a striking finding was that the total time showed marked similarity between two members of a pair, and the intra-class correlation coefficient was 0.98. Although dizygotic twins were not available in this experiment, the correlation CO-

efficient of random same-sexed pairs of a twin of a pair and a twin of another pair was 0.59. This figure is relatively high, but it is still markedly lower than that of monozygotic twins.

This experiment was carried out in a summer camp under a situation, which did not restrict the subjects in terms of performance time. The subjects seemingly per- formed as they liked. The author concluded from this finding that the total time represents an undifferentiated basic activity of individuals, which will possibly be modified by voluntary control.

This result stimulated us, in particular another collaborator of mine, TakumaZ4), who conducted the second experiment in a summer camp, in which the subjects were asked to listen to a story. The subjects were six male and two female pairs of monozygotic twins of the ages of 12 and 13. After the story had been told, they were personally asked how long the story took. The actual length of the story was 2 minutes 8 seconds, and its estimation by the subjects was between 1 minutes 20 seconds and 5 minutes. The intra-class correlation coefficient of monozygotic twins was 0.78, slightly lower than that of the first experiment. The correlation coefficient of same-sexed random pairs was 0.12. In this experiment the subjects were previously instructed only to listen to a story, and during listening to the story they were possibly consciously willing to understand and to memorize the story. There was no external standard to measure the elapsed time, and the subjects had to estimate it based up,on some unconscious internal sense, the quantity of which was indicated being possibly heritable.

The third experiment was carried out during an entrance examination of the Highschool (TakumaZ4)). The subjects were all male, and nine pairs of monozygotic twins and the same number of dizygotic twins of the ages of 1 1 to 13 were selected at random. They were individually examined and asked to make a sign at the moment they thought 10 or 30 seconds had passed after a sign was given by the investigator. The 10-seconds’ experiment was made three times, and the 30-seconds’ one, two times. The actual time length given by the subjects was between 6.8 seconds and 15.2 seconds in the first test, and it was between 20.3 and 44.8 seconds in the second test. The intra-class correlation coefficient of monozygotic twins was between 0.68 and 0.92, and that of dizygotic twins was between 0.03 and 0.39. Heritability calculated from these correlation coefficients was between 0.59 and 0.92, the latter figure is nearly complete heritability, 1.0. In this experiment there also was no external standard upon which noetic judgement would be based. The subjects had to judge the elapsed time consciously based upon some internal sense, the quantity of which is seemingly specific to an individual and is possibly highly heritable.

In other experiments of a similar nature but under different situations the identical result was not always obtained. This seems to indicate that the result is

188 E. Inouye

easily influenced by the situation of the experiment. Nevertheless, these findings suggest that the quantity of spontaneous activity and that of internal sense of time lapse are strongly controlled by genotype. It is also wggested that these behavior traits manifest themselves when higher noetic or voluntary functions are not effective, which may modify the inborn individual patterns in order to meet the requirements of external situations.

An evidence supporting this hypothesis was obtained in another experiment conducted by another collaborator, Kamitakels). Among his subjects of the ages of 10 to 13, nineteen monozygotic and the same number of same-sexed dizygotic twin pairs were selected at random. Kamitake, according to my suggestion, simply counted the number of blinkings of each subject under three different situations on various occasions. In the first situation the subjects were asked to gaze at a point in front of them. The variance between two members of monozygotic twins was slightly greater than that of dizygotic twins in this situation. Heritability* calculated from these variances was -0.09, which is nearly zero, and this figure is seen merely repre- senting an experimental error. In the second situation the subjects were asked not to blink, and heritability was 0.04, again nearly zezo. In the third situation the number of blinkings was counted during they were given psychological tests. The number of blinkings of individuals was distributed between 0 and 86 per minute, and heritability was 0.92. In this last state the subjects were under the situation of solving a problem, and they probably were not voluntarily controlling their blinking. In this state the individual patterns of this behavior are highly heritable, which are completely covered by voluntary control as indicated in the second test, or by simple awareness as suggested in the first test.

DIFFERENCE OF HERITABILITY OF EEG BETWEEN LEFT AND RIGHT HEMISPHERES

A finding in our preliminary study on EEG of normal twin subjects (Inouyeg)) was partly in agreement with the above-stated interpretation. In this study EEGs of two members of a pair were recorded simultaneously, and they were afternatively analysed by an automatic frequency analyser of Walter type. This apparatus records the integrated amount of waves in 10 seconds in each of six frequency bands from I to 30 cycle per second. Among seventeen twin pairs examined six monozygotic and six same-sexed dizygotic twin pairs of the ages of 11 and 12 were selected at random for the calculation of heritability.**

The upper half of Figure 2 shows the heritability of analysed EEG of left and right central leads at rest. The lower half shows the heritability of left central EEG under photic stimulations. It is seen in these diagrams that the highest heritability is usually observed in the alpha band under various conditions, but this is not the subject of present discussion. A fact which attracted my attention was the

* Heritability is also calculated by the formula "* ' ma where uE represents variance 2 - 2

U2ds

of same-sexed dizygotic and monozygotic twins, respectively.

band. for each status and for each cerebral hemisphere. * * For this purpose three successive integrated values were selected for each frequency

Genetic Basis of Human Behavior

Fig. 2. Heritability of Analysed and Integrated EEG for 10 Seconds (1) (Central Leads)

Left 1.0

Right

0.4

0.2

0

Under 0 -

189

At Rest

Low Frequency 1.0 r

4 4 8 a 3, i%

High Frequency

Photic Stimulation

0.2 (Left)

0 i Under 0-

difference between left and right sides at rest. It is seen that heritability of delta 2 is higher on the left side than on the right side. The situation is reverse in beta I , and heritability is higher on the right side than left side.

Figure 3 is the result of the same experiment on the same subjects recorded by another analyser of the same type. In two diagrams of the upper half showing the result at rest, beta 1 and beta 2 bands show higher heritrbility on the right side than the left side. There is no marked difference of heritability between the two sides in the delta band. Thus the side-difference in the beta 1 band appears to be significant. This result does no mean that the amount of beta 1 waves shows side-difference. Table 1 shows the result of anslysis of variance, in which a member of each of the total seventeen twin pairs was selected at random. It is shown that there is no significant side-difference in the amount of integrated waves in all frequency bands.

All subjects in this experiment are risht-handed, and the dominant cerebral hemisphere is left. In the dominant hemisphere the heritability of individual patterns of arousal activity as reflected in the faster frequency band is diminished, because the individual patterns may be modified by the impulses coming from inside and outside the central nervous system, as com- pared to the non-dominant hemisphere even at a rest state. In the non-dominant hemisphere the heritability of the individual patterns is high, because the arousal activity might be more autonomically functioning based upon genetically controlled individual patterns than the dominant hemisphere.

An interpretation of this finding might be as follows:

190

Between Left and Right Among 3 Measurements Among 17 Individuals

E. Inouye

Fig. 3. Heritability of Analysed and Integrated EEG for 10 Seconds (2) (Central Leads)

2.71 4.33 8.82 44.6 8.76 44.5

3.25"" 2 . 8 W 2.46" 2.31;: 2.38" 2.47" 22.6* 27.3" 146"" 16&W 89.9: 134%"

0.4

0.2

0

Under 0-

0.4

0.2

0

Under 0-

Between Left and Right 1.64 7.99 Among 3 Measurements 28.3" 1::; ~ 36.9" Among 17 Individuals 1.03 1.66 1.78

Left

1152" 1.26 3.44 276"" 37.0"' 24.9"

1.81*" 3.76"" 4.58""

4 8 2 8 0 P I Pz

Low Frequency

Right

At Rest

4 62 8 a P I 81

High Frequency

Photic Stimulation

(Left)

Table 1. Analysis of Variance (F-values) (Central Leads at Rest) ~~~ ~

Source of Variance i Delta 1 I Delta 2 1 Theta 1 Alpha 1 Beta I Beta 2

Analyser I

Analyser I1

Significantly high variance at O 0 1% level. Significantly low variance at * 5% and at ** 1% level.

In summerizing the foregoing discussions 1 feel we are beginning to form a rnethod- ology with which we can approach the genetic basis of human behavior. It is also felt that we should be able to uncover the genetically controlled behavioral traits


under certain conditions. The behavior should be free from voluntary or noetic workings, which are connected to external stimuli or regulations. If this condition to be realized, heritable individual patterns of behavior could be observed. The heritable behavioral traits are of non-voluntary, unconscious, undifferentiated, or autonomic character. I d o not say we absolutely excluded possible modifying factors affecting the inborn individual patterns of behavior. Also I d o not know the significance of these results and interpretations in the neurological sciences. But I frankly feel that :he individual differences of functions of the central nervous system should be paid proper attention by neurological and behavioral scientists.

REFERENCES

Brown, F. W.: Heredity in the psychoneuroses (Summary). Proc. Roy. SOC. Med. 35:

Cattel, R. B.: Research designs in psychological genetics with special reference to the multiple variance method. Am. J. Human Genet. 5: 76-93. 1953. Cattel, R. B. et al.: The inheritance of personality. A multiple variance analysis determination of approximated nature-nurture ratios for primary factors in Q-data. Am. Am. J. Human Genet. 7: 122-146, 1955. Galton, F.: The history of twins as a crilerium of relative powers of nature and nurture. J. Anthrop. Instit. 5: 391-406, 1875. Gottschaldt, K.: Die Methodik der Personlichkeitsforschung in der Erbpsychologie. Leipzig, 1942. Hayashi, S.: A genetical and clinical research in mental deficiency. Psychiat. Neurol. Jap. 58: 735-750, 1956 (Japanese w. English summary). Hsia, D. Y.: Inborn Errors of Metabolism, Year Book Publishers, Chicago, pp. 358, 1959. lnouye, E.: Eine Charakterstudie mittels Zwillingsmethode. Psychiat. Neurol. Sap. 55: 603-638, 1953 (Japanese w. German abstract). Inouye, E.: Heritability of individual EEG pattern. Recent Advance in Research of the Nervous System 7, Tokyo: 579-589, 1962 (Japanese w. English abstract). Inouye, E.: Recent studies on schizophrenia from the standpoint of clinical genetics. Clinical Psychiatry 5: 3-18, 1963 (Japanese). Inouye, E.: A discussion on neurosis theory from the standpoint of clinical genetics. Clinical Psychiatry 5: 859-870, 1963 (Japanese). Jackson, D. D.: A critique of the literature on the genetics of schizophrenia. The Etiology of Schizophrenia, ed. by Jackson, Basic Books, New York: 37-87, 1960. Jervis, G. A.: Phenylpyruvic oligophrenia. Genetics and the Inheritance of Integrated Neurological and Psychiatric Patterns, ed. by Hooker and Hare, Williams and Wilkins, Baltimore: 259-282, 1954. Kallrnann, F. J.: Heredity i,n Health and Mental Disorders, Norton, New York: 121- 124, 1953. Kamitake, S.: Soseiji no Kenkyu (Studies on Twins) 111, ed. by Fujita, Nihon Gakujutsu Shinkokai: 169-181, 1962 (Japanese). Lennox, W. G., Gibbs, E. L. and Gibbs, F. A.: Inheritance of cerebral dysrhythmia and epilepsy. Luxenburger, H.: Die Schizophrenia und ihre Erbkreis. Handbuch der Erbbiologie des Menschen V, ed. by G. Just, Springer, Berlin: 769-872, 1939.

785-790, 1942.

A study on hereditary control in blinking reflex.

Arch. Neurol. Psychiat. 44: 1155-1 183, 1940.

192 E. Inouye

26)

McInnes, R. G.: Observations on heredity in neurosis. Proc. Roy. Med. 30: 895-904, 1937. Mitsuda, H.: Klinisch-erbbiologische Untersuchung der endogenen Psychosen. Psy- chiat. Neurol. Jap. 55: 195-216, 1953 (Japanese w. German abstract). Okada, K.: Psychiat. Neurol. Jap. 49: 19-22, 42-46, 1946, 1947 (Japanese). Panse, F.: Erbpathologie der Psychopathien. Handbuch der Erbbiologie des Menschen V, ed. by G. Just, Springer, Berlin: 1089-1176, 1939. Suwa, N.: Psychiat. Neurol. Jap. 49: 55-59, 1947 (Japanese). Takagi, M.: Genetic-psychological study on the stratiform structure of personality. Soseiji no Kenkyu (Studies on Twins) 11, ed. by Uchimura, Nihon Gakujutsu Shinkokai, Tokyo: 220-242, 1956 (Japanese). Takuma, T.: Personal Communication. Uchimura, Y. et al.: ed. by Kinoshita, Tokyo: 1-105, 1949 (Japanese). Vandenberg, S. G.: logical test battery.

A study on personality by twin study method.

A study on personality by twin study method.

Charakterologie und Zwillingsforschung. Igaku no Shimpo VI.

The hereditary ability study; Hereditary components in a psycho- Am. J. Human Genets. 14: 220-237, 1962.

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GENETIC BASIS OF HUMAN BEHAVIOR