- Email: [email protected]
Aetiological factors in alcoholism: Some areas of research
Journal of Psychosomatic Research, Vol. 14, pp. 285 to 294. Pergamon Press, 1970. Printed in Northern Ireland
AETIOLOGICAL FACTORS IN ALCOHOLISM: SOME AREAS OF RESEARCH C. MCCANCE INTRODUCTION means different things to different people. Often the concept is a social one depending more upon disruptive behaviour of the person in question than upon the quantity he drinks or how he drinks it in terms of frequency and form. In other circles the term denotes a state of addiction or physical dependence in the current jargon, implying increased tolerance, withdrawal symptoms, and uncontrolled intake. Whether alcoholism is a disease or not, is often a question of rather heated debate because many have an emotional investment in looking upon it as such. Prominent amongst the disease protagonists are the alcoholics themselves and many of those who specialise in their treatment. For the investigator of aetiology it is not a question of primary importance. What he needs is an operational definition of the behaviour to be studied and this is most simply thought of in terms of the pattern of drinking and the quantity of alcohol ingested. Causation of any animal behaviour or biological variable is a perfectly valid concept whether disease, in the ‘process’ sense (implying a tangible pathology) plays a part or not. For example stature can be regarded as a product of genetic potential and nutritional fulfilment. Alcoholism is a form of ‘abnormal’ drinking, in the statistical sense, which has gradually developed from a more moderate intake with no clear cut off point. The causation and its concomitants can only be understood as a complicated interaction of many factors operating at different levels. This interaction can be represented simply by the following scheme.
ALCOHOLISM
Genetic Constitution
Pattern and Quantity of Alcohol Intake
Childhood Environment and Experiences
t __*
cultural, Social and Occupational Circumstances
+I Drug Effect
FIG. 1 The fainter arrows indicate that for example, a developed heavy drinking pattern may lead a person to become a barman (not his original trade), to steal drink (an action foreign to his previous personality) and to increase his intake further when drug tolerance has diminished the pleasant drug effect or when the drug effect becomes necessary to combat withdrawal symptoms. A very large literature on the aetiology of alcoholism has grown up, dealing with many ramifications of the problem. It is not my intention to review it comprehensively : attempts to do this, or to review certain areas in detail, have been made already. Amongst the best are Lester [l] and Edwards [2]. Lester covered much of the animal work discussing very critically the many technical pitfalls and the dangers of 285 6
286
C. MCCANCE
too glib an extrapolation of animal findings to man. This area of work hopes to elucidate the genetic contribution to the complex and further, to gain understanding of the biochemical and enzymatic mechanisms through which such contributions would be effected. The basic finding is that certain genetic strains of animals, especially mice and rats, drink more alcohol in a free choice situation than other strains of the same species, so that genetic differences may determine why some humans become alcoholics and others do not. Lester also devoted a section to studies upon humans which argue for a genetic predisposition to alcoholism but he was rightly critical of the work he reviewed. Edwards looked carefully at the evidence for genetic and environmental causation. He was mainly concerned with the formative environment and culture rather than the immediate situational environment. He also reviewed experimental work which demonstrated the alcohol withdrawal syndrome and the presence of physiological adaption to alcohol during the experimental drinking phase. He called these two aspects “the syndrome of chemical dependence” but he wondered if this was not the state of affairs which would develop in any human being who drank large amounts of alcohol and he threw the problem back as being basically-what makes a person chose to drink large quantities in the first place ? Edwards accepted the probability that genetic factors play some part in determining the appetite for alcohol but regarded environmental factors as probably the more important in determining the development of alcoholism. My contribution will be to daub a few blobs of paint on to my broad canvas, mainly at places where my own enquiries and those of my close colleagues have seemed to offer some original findings but I shall mention some other contributions. GENETIC
CONSTITUTION
The breeding experiments in mice and rats already mentioned at least point the possibility that there might be a genetic factor in the aetiology of drinking behaviour in man. Theoretically any genetic factor in alcoholism would not be likely to be a chromosomal anomaly. Autosomal trisomies cause fairly gross maldevelopment in many systems and trisomies of the sex chromosomes are usually associated with sub fertility and mental subnormality. We are nonetheless examining the chromosomes of a series of alcoholics. Single gene mutations of large effect are rare and show simple family patterns characteristic of their dominant, recessive or X-linked inheritance. If a genetic mechanism does exist in predisposing to alcoholism it is most likely to be through a polygenic inheritance determined by multiple allelism at determines blood groups, blood pressure, several gene loci. Such a mechanism stature and many other biological variables. If alcoholism were consistently associated with a variable which could be precisely identified and proved incontrovertibly to be genetically determined, this would strongly support a constitutional predisposition to alcoholism. Two areas of research along these lines are worthy of comment. [3] using the Hardy Rand Rittler plates, found Colour blindness. Cruz-Coke 25177 cirrhotics with colour blindness, 213 with a red-green type, l/3 with an he found 26/823 other hospital patients “undetermined” type. By comparison, with colour blindness. Again 213 were of a red-green type and l/3 “undetermined”. Cruz-Coke and Varela [4] followed this work up with a study of 100 male
Aetiological factors in alcoholism
287
alcoholics, 18 of whom were found to be colour blind and 633 male students, 30 of whom were colour blind. They used the same test as before but they did not mention what type of colour defect they found. Furthermore the age and intelligence of the control group almost certainly differed from the alcoholics and could have influenced the findings, since colour vision deteriorates with age. The same authors [5] tested 20 alcoholics and 10 university personnel with the Hardy Rand Rittler, the Ishihara and the Farnsworth-Munsell loo-Hue tests. They found that the mean number of errors amongst the alcoholics was 152 and amongst the ‘control’ subjects, was 58. To express the results in terms of means gives no indication as to what sort of colour vision defect is occurring. Furthermore, to do the Farnsworth test, requires application, good motivation and persistence: It is not performed reliably by children below ‘teen age because they have difficulty in grasping the concept of arranging a series of colour hues in order, for example, from blue through purple to pink. It seems quite likely that university personnel would make fewer global errors. The authors also tested the sons and daughters of the alcoholics and found “the mean cap errors of daughters was highly correlated to the mean errors of fathers and sons differed significantly”. They gave no values to support their statement but went on to say that “in our experience some daughters and all mothers of alcoholics show not only very low colour discrimination but also a classical pattern of dichromasy . . . . . . .“. They did not mention in which axis the dichromasy lay. It seems probable that the alcoholics’ mothers were wearing on in years : This might account in part for the findings. In discussion they suggested that “alcoholism is predetermined by a mutant X linked gene with a relatively high gene frequency”. They proposed that heterozygote carriers (the mothers) might have a biological advantage in terms of an increased fertility, and they quoted, in support of this, a finding from Canada [18] that alcoholics tended to come from large families. They also stated that the ratio of male:female alcoholics in a Santiago suburb was consistent with an X linked recessive trait. The Canadian study will be criticised in another part of this paper. Sex ratio in alcoholism, varying widely as it does in different parts of the world, may agree with an X linked hypothesis in Santiago, but in that case, it cannot support it elsewhere. The latest study from the Santiago group [6] using the Farnsworth 100 Hue test, examined 65 male alcoholics between 25 and 60 yr, some of their first degree relatives excluding excessive drinkers (parents, sibs or children, 18 males and 23 females in all), and a control group of 53 males and 44 females between 6 and 70 yr. They may, however, have excluded control subjects under 15 and over 60 later-this is not made clear. They found that male alcoholics made significantly more errors in the yellow-blue axis (Tritan and Tetartan) than the male controls and so did female relatives compared with female controls. With respect to the latter finding, it should be noted that the authors themselves were doubtful if their female controls were well matched. Gorrel [7] from Birmingham found only 3 red-green blind patients from a group of 55 alcoholics, against an expectation of 4.2, and 2 red-green blind patients amongst 26 cirrhotics, against an expectation of 2.0. It must be remembered, however, that using as he did, the Isihara test, he would not have picked up yellow-blue defects. In another communication, however, [8] he criticises the biochemical argument upon which the Santiago hypothesis was based.
288
C. MCCANCE
Thuline [9] using the Hardy Rand Rittler and Isihara tested 172 alcoholics and 647 non-alcoholics and found no significant difference in the incidence of colour blindness of protan or deutan type (red-green). The Santiago workers or their editors have left so much unsaid about their material, method and raw data that their findings cannot be refuted or accepted. Nothing has been said about the visual acuity, the fields or the fundal appearances of any of their subjects, nor about their state of arousal, intoxication or nutrition. Furthermore no mention was made of their use of tobacco. It would have been reassuring to see some individual protocols rather than having results expressed in means. Some of the papers contain disconcerting errors, such as claiming a significant difference which the figures did not confirm [6] and claiming that the results of Saraux et al. [lo] confirmed their finding of a “poor performance in the Tritan and Tetartan axis” [6], which they did not. Saraux found a red-green defect, not a blue yellow. Traditionally [II] and in recent French literature [lo] the toxic effects of ethyl alcohol and tobacco in excess, singly or in combination, have been accepted as causing amblyopia, though associated vitamin deficiency has been invoked [12]. These amblyopias are accompanied by defective colour vision in the red-green axis, sometimes detectable even before any loss of visual acuity. Failure to discriminate colours in the red-green axis is associated with lesions in the cones, optic nerve, chiasma or tract [13]. The common type of inherited colour blindness is also of the protan or deutan (red-green) type, but the experienced clinician can usually distinguish it from the acquired type. Lesions of the retina (involving the bipolar cells or ganglion cells) are usually associated with a blue-yellow (Tritan) axis of confusion. Such a form of colour blindness is found for example in diabetic retinopathy. A genetic blue-yellow defect is very rare indeed -0~0001 per cent in Caucasian males [ 111. It seems to behove the protagonists of the X linked recessive gene hypothesis, to show beyond reasonable doubt that a defect in colour vision in alcoholics if found, could not be a toxic manifestation or the result of a nutritional deficiency. Too much energy has been expended in trying to prove the hypothesis to be right. It could be simply disproved by showing recovery of colour vision in alcoholics originally found to be defective. Kinnear and the present author are planning a study along these lines. Blood groups. Camps and Dodd [14] reported that the proportion of ABH non-secretors amongst 318 alcoholic patients tested was significantly in excess of the proportion in a group of controls (p > 0.001). A further study [15] with which I have been closely associated has again shown an unexpectedly high proportion OF non-secretors amongst a series of 1000 alcoholics. But, the difference is almost entirely accounted for by an increase in Group A non-secretors at the expense of Group A secretors. This experimental finding could best be explained by postulating a direct effect of heavy alcohol consumption upon an individual’s secretor status. The overall frequency of blood Group A amongst these alcoholics was not greater than the controls, a finding which fails to confirm an earlier, cautious report from Colarado [16] on 939 alcoholics. The hypothesis that the increased number of nonsecretors amongst alcoholics is a genetically determined phenomenon would not be supported by finding children who secrete ABH substance from marriages of
Aetiological factors in alcoholism
289
non-secretor alcoholics and non-secretor wives. We are at present investigating this question. such as have been considered, Twin study. If there are no genetic “markers” the unravelling of polygenic mechanisms of inheritance depends upon large scale family studies and the more that environmental factors contribute to the final condition, the more blurred the picture becomes. Twin studies offer special opportunities in this difficult field and the immensely painstaking and long drawn out study from Finland by Partanen et al. is outstanding [ 171. These workers aimed to obtain extensive structured data at personal interview with each member of all male twin pairs born between 1920 and 1929 where both Obtaining their possible twin pairs from members of each pair were living in Finland. the birth register and deleting those where one or both of the twins had died, they were left with a target of 1044 pairs and they finally ran to earth 902 pairs. They subjected some of the appropriate data regarding drinking behaviour to factor analysis and identified three quantitative variables which they considered to be the most important. The first, which they called density, was largely a measure of the frequency of the drinking occasions. The second, called amount, was a product of the amount consumed on a single occasion, the duration of the occasion and the degree of intoxication. The last factor, lack of control, was related to the actual consumption level, the perceived drinking norms, and the dependence on alcohol. Qualitative These were abstainers against nondichotomous variables were also studied. abstainers, heavy users against other users, those arrested versus those not arrested for drunkenness and finally those showing addictive symptoms as opposed to those not showing these symptoms. It will be seen that their work is essentially a study of drinking behaviour rather than a study of alcoholism only. In dealing with the quantitative variables a heritability factor was calculated. The maximum value of one is obtained when both partners of all monoxygotic (MZ) pairs have the same score for the variable. Values will usually lie between zero and one, but theoretically a negative value is possible if dizygotic (DZ) pairs are more similar than MZ pairs. With the qualitative classification it is possible simply to compare the concordance rate of MZ and DZ pairs. The authors are extremely cautious and discuss very fully the various pitfalls, but they felt that of the drinking variables, density and amount show significant heritability (0.38 and 0.34 respectively). Lack of control showed little heritability in the whole sample but if those born between 1920 and 1925 were compared with those born between 1926 and 1929 there was a significant heritability factor in the younger group (0.54) whereas in the older there was none (-0*07). A further analysis indicated that there might be a common hereditary basis for amount and lack of control but that density appeared to be independently heritable. Of the dichotomies studied, abstaining and heavy use showed hereditary variation to a significant degree but arrests for drunkenness and addictive symptoms did not. The authors went on to study which environmental factors were associated with the most within pair variance amongst the MZ pairs. Discordance for urban residence was associated with significant Differences in density were greater where differences in density and lack of control. both members of the pair were married as opposed to one member married and one single and there was less difference still when both were single. There was also a larger difference in lack of control between the twins if both were married than if
290
C. MCCANCE
they were both single or only one married. For both density and lack of control there was a larger difference between the older pairs than between the younger pairs. The amount factor however was not significantly affected by discordant urbanization or marital status. The authors adduce that “Social Structure affects drinking behaviour even when genetic sources of variation are absent”. In a nutshell, what seems to be inherited to some extent is how much and how often a person likes to drink, but addiction and the social consequences of drinking too much, i.e. the bare bones of what most people would call alcoholism, are not. The drinking behaviour to which Partanen and his colleagues have ascribed a significant heritability factor seems to bear much more relationship to what has been shown to be heritable in mice and rats than the usual concepts of alcoholism. CHILDHOOD
ENVIRONMENT
AND
EXPERIENCES
FamiZy size. Smart [18] studying 242 alcoholics from alcoholism clinics in Ontario found more alcoholics coming from sibship sizes of five or over than would have been expected by comparison to the distribution of sibship sizes in 1931. Birtchnell [19] working on Aberdeen Case Register material and a general population sample does not confirm this finding. Indeed, he finds that only children comprise 7.1 per cent of his total patient group (all psychiatric diagnoses) but 9.5 per cent of the alcoholics, this difference being significant at the 5 per cent level. For other sibship sizes there are no differences. Birth order. Bakan [20] studying a sample of 1493 males convicted of public intoxication in Indiana concluded that the likelihood of contributing to an alcoholic population increases as the number of older sibs increases and that persons who were oldest children contribute significantly less than persons who were youngest children. Smart [18] in his discussion quoted three further authors as having found an overrepresentation of later borns in alcoholic groups but Erlenmeyer-Kimling et al. [21] showed that this pattern also obtained for schizophrenics and samples of other subjects (male homosexuals, juvenile delinquent boys, adult tuberculosis patients, American men of science and others). Price and Hare [22,23] have now re-emphasised the biases which may influence studies of this sort. Particularly important is that families were falling in size from the beginning of this century until 1940. In these circumstances, any population born in this period could be expected to have an excess of last borns in large families, first borns in small sibships and a slight overall excess of last borns. Another important source of bias which they point out and which seems particularly applicable to samples of alcoholics isthe effect of differential migration to the source of ascertainment of the patients in the sample studied. Confirming the importance of falling family size, Birtchnell has now shown that the distribution of birth order in a sample of the general population again shows a significant excess of later borns in large sibships and early borns in small sibships. Thus for sibships of two there were more first than second borns in the general The trend was slightly more marked in the group of all population sample: psychiatric patients and more marked still in the alcoholics but he feels that much importance should not be placed on this finding. Childhood bereavement. Hilgard and Newman [24, 251 studied 678 male and 251 female patients entering hospital diagnosed as alcoholic and 631 males and 930 females diagnosed as schizophrenic and compared these with a group of 1096
Aetiological factors in alcoholism
291
controls from the general population served by the hospital. All subjects were white, native born and between 20 and 49 yr. Their findings were rather fragmentary and seemed to have no clear message; for instance female alcoholics and schizophrenics who lost mothers lost them excessively before the age of 3, but males did not differ from controls for mean age at loss: and for male and female alcoholics between the ages of 20 and 39, parent loss prior to the age of 19 was greater than in the controls. Again Dennehy [26] reported a collection of associations between various sub-groups of depressive, schizophrenic, alcoholic and drug-addicted patients, and childhood bereavement, which was bewildering and seemed to have no clear meaning. Certainly nothing specific on alcoholism emerged. Birtchnell has recently found in the North East of Scotland not only that there is no difference between the various diagnostic groups and parental death in childhood, but that his patient group did not differ from a general population sample. These attempts to obtain epidemiological support for hypotheses postulating aetiological factors from early environment are disappointing but underline the complexity of the problem and the ease with which the unwary researcher may tumble to wrong conclusions. PERSONAL QUALITIES To what extent certain personal qualities (such as the ways of answering a personality inventory) are enduring, established before the onset of alcoholism and not profoundly changed by it, is uncertain but a study of the personality profiles of alcoholics compared with normals might provide some aetiological inferences. If alcohol appetite; inherited as an independent variable, was the main aetiological force in the production of alcoholism, the personality profiles of alcoholics might be expected to resemble those of the general population [27]. An analysis of personality factors in 123 male alcoholics from North-East Scotland did not show this [27]. The Cattell 16 Personality Factor Questionnaire [28] was administered to consecutive admissions as part of an investigation into the treatment of alcoholics in this region [29]. The standard scores of these alcoholics were compared with those of 100 normal subjects from the Aberdeen area described by McAllister [30]. The alcoholics differed from them at the 0.1 per cent level in being emotionally unstable as opposed to mature or calm (low score on factor C); more casual or undependable as opposed to conscientious (low score on factor G), more shy (a low H score), more unrealistic or eccentric as opposed to practical (high M score), more insecure or guilt prone (high 0 score), and more tense (high 44 score). Despite the cultural differences which one would expect to influence the normal scores from North-East Scotland as opposed to the American norms, the Scottish alcoholic group also differed significantly from Cattell’s norms in all the factors mentioned above except factor M. Walton [31] described his findings using the 16 PF on a group of Although differing from our group for some of the factors 38 Edinburgh alcoholics. they did not differ for any of the factors already mentioned. It would be mistaken to jump to the conclusion that a profile typical of alcoholism had been demonstrated. McAllister [30] has shown that a group of neurotics from North-East Scotland also differed significantly from his normal group in exactly the same direction as our alcoholics for factors C, G, 0 and Q4 and his group of patients with manic depressive illness and paranoid states differed in the same way for factor M. The only factor on which none of his patient groups differed from his
292
C. MCCANCE
norms and on which our alcoholics did differ, was for factor H, the factor which suggested that the alcoholics were unusually shy. It might be concluded that the personality profiles of developed alcoholics differ significantly in a number of respects from normals but not from many other psychiatric patients, particularly neurotics and that a specific genetic factor certainly does not exert a sufficient effect to make personality irrelevant. It might, however, dispose some neurotics to solve their problems through drink. THE
ENVIRONMENT
IN
LATER
LIFE
Social and demographic data about a cohort of 194 alcoholics from North-East Scotland were gathered in connection with the treatment study already mentioned [26]. The Aberdeen case register was searched by computer to find a patient with any psychiatric diagnosis other than alcoholism, to match each individual in the cohort of alcoholics for sex, age and place of residence. This control group of patients was compared with the alcoholic patients for various social data which are collected routinely from all patients who enter the psychiatric services [32]. It was found that there were 34 seafarers amongst the alcoholics but only 9 amongst the other patients, a difference significant at the 0.1 per cent level. This high incidence of a sea-faring occupation (especially commercial fishing) amongst our alcoholic patients might seem to show that the heavy drinking customs amongst some sections of the North-East fishing fraternity, lead some men to alcoholism. What could be more understandable than being seduced into heavy drinking with a small group of shipmates when the dangers braved together are over for a spell, with a good catch to celebrate perhaps, and a pocketful of money to spend. But assumptions of cause and effect are treacherous. Brun-Gulbrandsen [33] has shown amongst Norwegian seamen, who also drink very heavily but who differ from our group in being almost entirely mercantile mariners as opposed to fishermen, that within the group of seamen the incidence of alcohol abuse was substantially higher amongst those with a low educational level, amongst those from orphanages, foster homes or homes where the parents have died or divorced although the longer the and in those with high neuroticism scores. Furthermore, service at sea, the more frequent the abuse of alcohol for the group as a whole, those with good educational level, good home background and no neuroticisms did not contribute to this trend. Thus the background and personality factors of the individual seem to be more important than the job environment and, indeed, the finding of a correlation between alcoholism and sea-faring could be explicable on the hypothesis that potential drinkers choose such a way of life. EPILOGUE
The aetiology of alcoholism can only be seen as a complicated interaction of factors and a model which represents the main elements in this interaction has been proposed. This model may clarify the relevance of individual research contributions to the overall picture and may help to formulate hypotheses for testing by further experiment. Dalen [34] has urged for psychiatric research in general that hypotheses should be simple and easily refuted. When the overall situation is clearly not simple then it has to be broken down into simpler components. Research work on different aspects of the problem from different countries
293
Aetiological factors in alcoholism
would contribute more to a composite pool of knowledge if an operational definition of alcoholism as precise as possible were adopted internationally. The W.H.O. definition of alcoholism [35] is not suitable for scientists. A simpler description in terms of the quantity of ethanol consumed per day with an attempt also to recognise the fluctuations which occur in some styles of drinking, might be less ambiguous. SUMMARY
Alcoholism, disease or otherwise, is manifest by a behavioural complex. It is proposed that causation must be regarded as an interaction of many factors operating at different levels. The pattern and quantity of alcohol intake will be influenced by three major factors; personal factors, social factors and drug factors. The personal factors, in their turn, will have been largely determined by an interaction between the genetic deal and the childhood environment. But heavy drinking, if it has developed will itself have an effect on the personal qualities, the social circumstances and the drug effects. Three aspects of research upon possible genetic factors are reviewed; the association between alcoholism and colour blindness reported from Santiago, the association between alcoholism and the non-secretion of blood group substances found in Great Britain, and the contribution from a Finnish twin study. No final conclusions can yet be drawn from the colour vision and blood group work but it seems more likely that alcohol has caused the observed anomalies than that they mark a genotypic entity associated with a predisposition to alcoholism. The twin study suggests that genes may determine to some extent, the appetite for alcohol. Research into family size, birth order and childhood bereavement is looked at and dismissed as contributing little or nothing to clarifying the effect of early environment upon the development of alcoholism. Discussion of personal qualities is confined to a brief report on some 16 P. F. results on 123 Aberdeen alcoholics. They differed from Aberdeen controls for their scores on factors C, G, H, M, 0 and 44 but these differences were largely shared by a group of neurotics. The interplay between alcoholism and occupation is exemplified by the prevalence of alcoholism amongst seamen from the North East of Scotland. In conclusion, a plea is made for a more simple operational definition of drinking behaviour in order that individual research efforts on different aspects of the problem in different countries, might each contribute more to a composite picture. Acknowledgements-I am greatly indebted to Mr. Paul Kinnear and Mr. P. K. Ray for giving me insight into some of the technical aspects of colour vision and to Dr. John Birtchnell for allowing me to communicate some of his unpublished data*. REFERENCES 1. LESTERD. Self-selection of alcohol by animals, human variation, and the etiology of alcohohsm: a critical review. Q. J. Stud. Alcohol 27, 395 (1966). 2. EDWARDSG. The status of alcoholism as a disease. In Modern Trends in Drug Dependence and Alcoholism, (Edited by PHILLIPWNR. V.), Chap. 8. pp. 140-162. Butterworths, London (1970). 3. CRUZ-COKER. Colour-blindness and cirrhosis of the liver. Lancet 1, 1131 (1965). 4. CRUZ-COKER. and VARELAA. Colour-blindness and alcohol addiction. Lancet 2, 1348 (1965). 5. CRUZ-COKER. and VARELAA. Inheritance of alcoholism: its association with colour-blindness. Lancet 2, 1282 (1966). * Some of Dr. Birchnell’s data have now been published in Br. J. Psychiat.
116,281
(1970).
C. MCCANCE
294
6. VARELA A., RIVERA L., MARDONESJ. and CRUZ-COKE R. Color vision defects in non-alcoholic relatives of alcoholic patients. Br. J. Addict. 64, 67 (1969). I. GORRELLG. J. A study of defective vision with the Ishihara test plates. Ann. Hum. Genet. 31,
39 (1967). 8. GORRELLG. J. Inheritance of alcoholism. Lancet 1, 274 (1967). 9. THULINEH. C. Inheritance of alcoholism. Lancet 1, 274 (1967). 10. SARAUX H., LABET R. and BIAIS B. Aspects actuels de la n&rite optique de l’ethylique. Annls Oculist. 199, 943 (1966). Vol. 4. 11. DUKE-ELDER S. The physiology of the eye and of vision. System of Ophthalmology. uu. 635-642. Henrv Kimuton. London (1968). of ihe eye. pp. 221-222. Charles C. Thomas, Springfield, Ill. (1962). 12. GRANT W. M. To&ologi of diabetics. Master of Science thesis, Edinburgh 13. KINNEAR P. R. The colour discrimination
University (1965). 14. CAMPS F. E. and DODD B. E. Increase in the incidence of non-secretors of ABH blood group substances among alcoholic patients Br. Med. J. 1, 30 (1967). 1.5. CAMPS F. E.. DODD B. E. and LINCOLNP. J. The frequencies of secretors and non-secretors of ABH blood group substances among 1000 alcoholic patients. Br. Med. J. 4, 457 (1969). 16. NORDMO S. H. Blood groups in schizophrenia, alcoholism, and mental deficiency. Am. J. Psychiat. 116,460 (1959). study on 17. PARTANENJ., BRUUN K. and MARKKANENT. Inheritance of drinking behaviour-a intellipence. oersonalitv, and use of alcohol of adult twins. The Finnish Foundation for Alcohol
Stud&, Publication No. 14. Helsmki (1966j. 18. SMARTR. G. Alcoholism, birth order, and family size. J. Abnorm. Sot. Psycho/. 66, 17 (1963). 19. BIRTCHNELLJ. Personal communication. 20. BAKAN D. The relationship between alcoholism and birth rank. Q. Jl Stud. Alcohol 10, 434 (1949). L., VAN DEN BOSCHE. and DENHAMB. The problem of birth order and 21. ERLENMEYER-KIMLING schizophrenia: a negative conclusion. Br. J. Psychiat. 115,659 (1969). 22. PRICEJ. S. and HARE E. H. Birth order studies: some sources of bias. Br. J. Psychiat. 115,633
(1969). 23. HARE E. H. and PRICEJ. S. Birth order and family size: bias caused by changes in birth rate. Br. J. Psvchiat. 115.647 (1969). 24. HILGA& J. R. and NEWMAN M. F. Early parental deprivation in schizophrenia and alcoholism. Am. J. Orthopsychiat. 33,409 (1963). 25. HILGARD J. R. and NEWMAN M. F. Parental loss by death in childhood as an etiological factor among schizophrenic and alcoholic patients compared with a non-patient community sample. J. Nerv. Ment. Dis. 137, 14 (1963). 26. DENNEHYC. M. Childhood bereavement and psychiatric illness. Br. J. Psychiat. 112, 1049 (1966). 27. SIM S. J. Some social and personality correlates of male alcoholics in North-East Scotland. Thesis for degree of M.A. (Hons.) Psychology. Univ. of Aberdeen (1969). 28. CATTELL R. B. and STICE G. G. Handbook of the Sixteen Personality Factor Questionnaire.
Champaigne, Illinois, I.P.A.T. (1957). 29. MCCANCE C. and MCCANCE P. F. Alcoholism 30. 31. 32. 33.
34. 35.
in North-East Scotland: its treatment and outcome. Br. J. Psychiat. 115, 189 (1969). MCALLISTERJ. Foulds “Continuum of personal illness” and the 16 P.F. Br. J. Psychiat. 114, 53 (1968). WALTON H. J. Personality as a determinant of the form of alcoholism. Br. J. Psychiat. 114, 761 (1968). BALDWINJ. A., INNESG., MILLAR W. M., SHARP G. A. and DORRICOTI.N. A psychiatric case register in North-East Scotland. Br. J. Prev. Sot. Med. 19, 38 (1965). BRUN-GULBRANDSEN S. and IRGENS-JENSEN 0. Abuse of alcohol among seamen. Br. J. Addict. 62, 19 (1967). DAL~N P. Causal explanations in psychiatry: a critique of some current concepts. Br. J. Psychiat. 115, 129 (1969). WORLD HEALTH ORGANISATION.Expert Committee on Mental Health. Alcohol Sub-committee Second Report. W.H.O. Technical Report Series No. 48. (1952).
AETIOLOGICAL FACTORS IN ALCOHOLISM: SOME AREAS OF RESEARCH C. MCCANCE INTRODUCTION means different things to different people. Often the concept is a social one depending more upon disruptive behaviour of the person in question than upon the quantity he drinks or how he drinks it in terms of frequency and form. In other circles the term denotes a state of addiction or physical dependence in the current jargon, implying increased tolerance, withdrawal symptoms, and uncontrolled intake. Whether alcoholism is a disease or not, is often a question of rather heated debate because many have an emotional investment in looking upon it as such. Prominent amongst the disease protagonists are the alcoholics themselves and many of those who specialise in their treatment. For the investigator of aetiology it is not a question of primary importance. What he needs is an operational definition of the behaviour to be studied and this is most simply thought of in terms of the pattern of drinking and the quantity of alcohol ingested. Causation of any animal behaviour or biological variable is a perfectly valid concept whether disease, in the ‘process’ sense (implying a tangible pathology) plays a part or not. For example stature can be regarded as a product of genetic potential and nutritional fulfilment. Alcoholism is a form of ‘abnormal’ drinking, in the statistical sense, which has gradually developed from a more moderate intake with no clear cut off point. The causation and its concomitants can only be understood as a complicated interaction of many factors operating at different levels. This interaction can be represented simply by the following scheme.
ALCOHOLISM
Genetic Constitution
Pattern and Quantity of Alcohol Intake
Childhood Environment and Experiences
t __*
cultural, Social and Occupational Circumstances
+I Drug Effect
FIG. 1 The fainter arrows indicate that for example, a developed heavy drinking pattern may lead a person to become a barman (not his original trade), to steal drink (an action foreign to his previous personality) and to increase his intake further when drug tolerance has diminished the pleasant drug effect or when the drug effect becomes necessary to combat withdrawal symptoms. A very large literature on the aetiology of alcoholism has grown up, dealing with many ramifications of the problem. It is not my intention to review it comprehensively : attempts to do this, or to review certain areas in detail, have been made already. Amongst the best are Lester [l] and Edwards [2]. Lester covered much of the animal work discussing very critically the many technical pitfalls and the dangers of 285 6
286
C. MCCANCE
too glib an extrapolation of animal findings to man. This area of work hopes to elucidate the genetic contribution to the complex and further, to gain understanding of the biochemical and enzymatic mechanisms through which such contributions would be effected. The basic finding is that certain genetic strains of animals, especially mice and rats, drink more alcohol in a free choice situation than other strains of the same species, so that genetic differences may determine why some humans become alcoholics and others do not. Lester also devoted a section to studies upon humans which argue for a genetic predisposition to alcoholism but he was rightly critical of the work he reviewed. Edwards looked carefully at the evidence for genetic and environmental causation. He was mainly concerned with the formative environment and culture rather than the immediate situational environment. He also reviewed experimental work which demonstrated the alcohol withdrawal syndrome and the presence of physiological adaption to alcohol during the experimental drinking phase. He called these two aspects “the syndrome of chemical dependence” but he wondered if this was not the state of affairs which would develop in any human being who drank large amounts of alcohol and he threw the problem back as being basically-what makes a person chose to drink large quantities in the first place ? Edwards accepted the probability that genetic factors play some part in determining the appetite for alcohol but regarded environmental factors as probably the more important in determining the development of alcoholism. My contribution will be to daub a few blobs of paint on to my broad canvas, mainly at places where my own enquiries and those of my close colleagues have seemed to offer some original findings but I shall mention some other contributions. GENETIC
CONSTITUTION
The breeding experiments in mice and rats already mentioned at least point the possibility that there might be a genetic factor in the aetiology of drinking behaviour in man. Theoretically any genetic factor in alcoholism would not be likely to be a chromosomal anomaly. Autosomal trisomies cause fairly gross maldevelopment in many systems and trisomies of the sex chromosomes are usually associated with sub fertility and mental subnormality. We are nonetheless examining the chromosomes of a series of alcoholics. Single gene mutations of large effect are rare and show simple family patterns characteristic of their dominant, recessive or X-linked inheritance. If a genetic mechanism does exist in predisposing to alcoholism it is most likely to be through a polygenic inheritance determined by multiple allelism at determines blood groups, blood pressure, several gene loci. Such a mechanism stature and many other biological variables. If alcoholism were consistently associated with a variable which could be precisely identified and proved incontrovertibly to be genetically determined, this would strongly support a constitutional predisposition to alcoholism. Two areas of research along these lines are worthy of comment. [3] using the Hardy Rand Rittler plates, found Colour blindness. Cruz-Coke 25177 cirrhotics with colour blindness, 213 with a red-green type, l/3 with an he found 26/823 other hospital patients “undetermined” type. By comparison, with colour blindness. Again 213 were of a red-green type and l/3 “undetermined”. Cruz-Coke and Varela [4] followed this work up with a study of 100 male
Aetiological factors in alcoholism
287
alcoholics, 18 of whom were found to be colour blind and 633 male students, 30 of whom were colour blind. They used the same test as before but they did not mention what type of colour defect they found. Furthermore the age and intelligence of the control group almost certainly differed from the alcoholics and could have influenced the findings, since colour vision deteriorates with age. The same authors [5] tested 20 alcoholics and 10 university personnel with the Hardy Rand Rittler, the Ishihara and the Farnsworth-Munsell loo-Hue tests. They found that the mean number of errors amongst the alcoholics was 152 and amongst the ‘control’ subjects, was 58. To express the results in terms of means gives no indication as to what sort of colour vision defect is occurring. Furthermore, to do the Farnsworth test, requires application, good motivation and persistence: It is not performed reliably by children below ‘teen age because they have difficulty in grasping the concept of arranging a series of colour hues in order, for example, from blue through purple to pink. It seems quite likely that university personnel would make fewer global errors. The authors also tested the sons and daughters of the alcoholics and found “the mean cap errors of daughters was highly correlated to the mean errors of fathers and sons differed significantly”. They gave no values to support their statement but went on to say that “in our experience some daughters and all mothers of alcoholics show not only very low colour discrimination but also a classical pattern of dichromasy . . . . . . .“. They did not mention in which axis the dichromasy lay. It seems probable that the alcoholics’ mothers were wearing on in years : This might account in part for the findings. In discussion they suggested that “alcoholism is predetermined by a mutant X linked gene with a relatively high gene frequency”. They proposed that heterozygote carriers (the mothers) might have a biological advantage in terms of an increased fertility, and they quoted, in support of this, a finding from Canada [18] that alcoholics tended to come from large families. They also stated that the ratio of male:female alcoholics in a Santiago suburb was consistent with an X linked recessive trait. The Canadian study will be criticised in another part of this paper. Sex ratio in alcoholism, varying widely as it does in different parts of the world, may agree with an X linked hypothesis in Santiago, but in that case, it cannot support it elsewhere. The latest study from the Santiago group [6] using the Farnsworth 100 Hue test, examined 65 male alcoholics between 25 and 60 yr, some of their first degree relatives excluding excessive drinkers (parents, sibs or children, 18 males and 23 females in all), and a control group of 53 males and 44 females between 6 and 70 yr. They may, however, have excluded control subjects under 15 and over 60 later-this is not made clear. They found that male alcoholics made significantly more errors in the yellow-blue axis (Tritan and Tetartan) than the male controls and so did female relatives compared with female controls. With respect to the latter finding, it should be noted that the authors themselves were doubtful if their female controls were well matched. Gorrel [7] from Birmingham found only 3 red-green blind patients from a group of 55 alcoholics, against an expectation of 4.2, and 2 red-green blind patients amongst 26 cirrhotics, against an expectation of 2.0. It must be remembered, however, that using as he did, the Isihara test, he would not have picked up yellow-blue defects. In another communication, however, [8] he criticises the biochemical argument upon which the Santiago hypothesis was based.
288
C. MCCANCE
Thuline [9] using the Hardy Rand Rittler and Isihara tested 172 alcoholics and 647 non-alcoholics and found no significant difference in the incidence of colour blindness of protan or deutan type (red-green). The Santiago workers or their editors have left so much unsaid about their material, method and raw data that their findings cannot be refuted or accepted. Nothing has been said about the visual acuity, the fields or the fundal appearances of any of their subjects, nor about their state of arousal, intoxication or nutrition. Furthermore no mention was made of their use of tobacco. It would have been reassuring to see some individual protocols rather than having results expressed in means. Some of the papers contain disconcerting errors, such as claiming a significant difference which the figures did not confirm [6] and claiming that the results of Saraux et al. [lo] confirmed their finding of a “poor performance in the Tritan and Tetartan axis” [6], which they did not. Saraux found a red-green defect, not a blue yellow. Traditionally [II] and in recent French literature [lo] the toxic effects of ethyl alcohol and tobacco in excess, singly or in combination, have been accepted as causing amblyopia, though associated vitamin deficiency has been invoked [12]. These amblyopias are accompanied by defective colour vision in the red-green axis, sometimes detectable even before any loss of visual acuity. Failure to discriminate colours in the red-green axis is associated with lesions in the cones, optic nerve, chiasma or tract [13]. The common type of inherited colour blindness is also of the protan or deutan (red-green) type, but the experienced clinician can usually distinguish it from the acquired type. Lesions of the retina (involving the bipolar cells or ganglion cells) are usually associated with a blue-yellow (Tritan) axis of confusion. Such a form of colour blindness is found for example in diabetic retinopathy. A genetic blue-yellow defect is very rare indeed -0~0001 per cent in Caucasian males [ 111. It seems to behove the protagonists of the X linked recessive gene hypothesis, to show beyond reasonable doubt that a defect in colour vision in alcoholics if found, could not be a toxic manifestation or the result of a nutritional deficiency. Too much energy has been expended in trying to prove the hypothesis to be right. It could be simply disproved by showing recovery of colour vision in alcoholics originally found to be defective. Kinnear and the present author are planning a study along these lines. Blood groups. Camps and Dodd [14] reported that the proportion of ABH non-secretors amongst 318 alcoholic patients tested was significantly in excess of the proportion in a group of controls (p > 0.001). A further study [15] with which I have been closely associated has again shown an unexpectedly high proportion OF non-secretors amongst a series of 1000 alcoholics. But, the difference is almost entirely accounted for by an increase in Group A non-secretors at the expense of Group A secretors. This experimental finding could best be explained by postulating a direct effect of heavy alcohol consumption upon an individual’s secretor status. The overall frequency of blood Group A amongst these alcoholics was not greater than the controls, a finding which fails to confirm an earlier, cautious report from Colarado [16] on 939 alcoholics. The hypothesis that the increased number of nonsecretors amongst alcoholics is a genetically determined phenomenon would not be supported by finding children who secrete ABH substance from marriages of
Aetiological factors in alcoholism
289
non-secretor alcoholics and non-secretor wives. We are at present investigating this question. such as have been considered, Twin study. If there are no genetic “markers” the unravelling of polygenic mechanisms of inheritance depends upon large scale family studies and the more that environmental factors contribute to the final condition, the more blurred the picture becomes. Twin studies offer special opportunities in this difficult field and the immensely painstaking and long drawn out study from Finland by Partanen et al. is outstanding [ 171. These workers aimed to obtain extensive structured data at personal interview with each member of all male twin pairs born between 1920 and 1929 where both Obtaining their possible twin pairs from members of each pair were living in Finland. the birth register and deleting those where one or both of the twins had died, they were left with a target of 1044 pairs and they finally ran to earth 902 pairs. They subjected some of the appropriate data regarding drinking behaviour to factor analysis and identified three quantitative variables which they considered to be the most important. The first, which they called density, was largely a measure of the frequency of the drinking occasions. The second, called amount, was a product of the amount consumed on a single occasion, the duration of the occasion and the degree of intoxication. The last factor, lack of control, was related to the actual consumption level, the perceived drinking norms, and the dependence on alcohol. Qualitative These were abstainers against nondichotomous variables were also studied. abstainers, heavy users against other users, those arrested versus those not arrested for drunkenness and finally those showing addictive symptoms as opposed to those not showing these symptoms. It will be seen that their work is essentially a study of drinking behaviour rather than a study of alcoholism only. In dealing with the quantitative variables a heritability factor was calculated. The maximum value of one is obtained when both partners of all monoxygotic (MZ) pairs have the same score for the variable. Values will usually lie between zero and one, but theoretically a negative value is possible if dizygotic (DZ) pairs are more similar than MZ pairs. With the qualitative classification it is possible simply to compare the concordance rate of MZ and DZ pairs. The authors are extremely cautious and discuss very fully the various pitfalls, but they felt that of the drinking variables, density and amount show significant heritability (0.38 and 0.34 respectively). Lack of control showed little heritability in the whole sample but if those born between 1920 and 1925 were compared with those born between 1926 and 1929 there was a significant heritability factor in the younger group (0.54) whereas in the older there was none (-0*07). A further analysis indicated that there might be a common hereditary basis for amount and lack of control but that density appeared to be independently heritable. Of the dichotomies studied, abstaining and heavy use showed hereditary variation to a significant degree but arrests for drunkenness and addictive symptoms did not. The authors went on to study which environmental factors were associated with the most within pair variance amongst the MZ pairs. Discordance for urban residence was associated with significant Differences in density were greater where differences in density and lack of control. both members of the pair were married as opposed to one member married and one single and there was less difference still when both were single. There was also a larger difference in lack of control between the twins if both were married than if
290
C. MCCANCE
they were both single or only one married. For both density and lack of control there was a larger difference between the older pairs than between the younger pairs. The amount factor however was not significantly affected by discordant urbanization or marital status. The authors adduce that “Social Structure affects drinking behaviour even when genetic sources of variation are absent”. In a nutshell, what seems to be inherited to some extent is how much and how often a person likes to drink, but addiction and the social consequences of drinking too much, i.e. the bare bones of what most people would call alcoholism, are not. The drinking behaviour to which Partanen and his colleagues have ascribed a significant heritability factor seems to bear much more relationship to what has been shown to be heritable in mice and rats than the usual concepts of alcoholism. CHILDHOOD
ENVIRONMENT
AND
EXPERIENCES
FamiZy size. Smart [18] studying 242 alcoholics from alcoholism clinics in Ontario found more alcoholics coming from sibship sizes of five or over than would have been expected by comparison to the distribution of sibship sizes in 1931. Birtchnell [19] working on Aberdeen Case Register material and a general population sample does not confirm this finding. Indeed, he finds that only children comprise 7.1 per cent of his total patient group (all psychiatric diagnoses) but 9.5 per cent of the alcoholics, this difference being significant at the 5 per cent level. For other sibship sizes there are no differences. Birth order. Bakan [20] studying a sample of 1493 males convicted of public intoxication in Indiana concluded that the likelihood of contributing to an alcoholic population increases as the number of older sibs increases and that persons who were oldest children contribute significantly less than persons who were youngest children. Smart [18] in his discussion quoted three further authors as having found an overrepresentation of later borns in alcoholic groups but Erlenmeyer-Kimling et al. [21] showed that this pattern also obtained for schizophrenics and samples of other subjects (male homosexuals, juvenile delinquent boys, adult tuberculosis patients, American men of science and others). Price and Hare [22,23] have now re-emphasised the biases which may influence studies of this sort. Particularly important is that families were falling in size from the beginning of this century until 1940. In these circumstances, any population born in this period could be expected to have an excess of last borns in large families, first borns in small sibships and a slight overall excess of last borns. Another important source of bias which they point out and which seems particularly applicable to samples of alcoholics isthe effect of differential migration to the source of ascertainment of the patients in the sample studied. Confirming the importance of falling family size, Birtchnell has now shown that the distribution of birth order in a sample of the general population again shows a significant excess of later borns in large sibships and early borns in small sibships. Thus for sibships of two there were more first than second borns in the general The trend was slightly more marked in the group of all population sample: psychiatric patients and more marked still in the alcoholics but he feels that much importance should not be placed on this finding. Childhood bereavement. Hilgard and Newman [24, 251 studied 678 male and 251 female patients entering hospital diagnosed as alcoholic and 631 males and 930 females diagnosed as schizophrenic and compared these with a group of 1096
Aetiological factors in alcoholism
291
controls from the general population served by the hospital. All subjects were white, native born and between 20 and 49 yr. Their findings were rather fragmentary and seemed to have no clear message; for instance female alcoholics and schizophrenics who lost mothers lost them excessively before the age of 3, but males did not differ from controls for mean age at loss: and for male and female alcoholics between the ages of 20 and 39, parent loss prior to the age of 19 was greater than in the controls. Again Dennehy [26] reported a collection of associations between various sub-groups of depressive, schizophrenic, alcoholic and drug-addicted patients, and childhood bereavement, which was bewildering and seemed to have no clear meaning. Certainly nothing specific on alcoholism emerged. Birtchnell has recently found in the North East of Scotland not only that there is no difference between the various diagnostic groups and parental death in childhood, but that his patient group did not differ from a general population sample. These attempts to obtain epidemiological support for hypotheses postulating aetiological factors from early environment are disappointing but underline the complexity of the problem and the ease with which the unwary researcher may tumble to wrong conclusions. PERSONAL QUALITIES To what extent certain personal qualities (such as the ways of answering a personality inventory) are enduring, established before the onset of alcoholism and not profoundly changed by it, is uncertain but a study of the personality profiles of alcoholics compared with normals might provide some aetiological inferences. If alcohol appetite; inherited as an independent variable, was the main aetiological force in the production of alcoholism, the personality profiles of alcoholics might be expected to resemble those of the general population [27]. An analysis of personality factors in 123 male alcoholics from North-East Scotland did not show this [27]. The Cattell 16 Personality Factor Questionnaire [28] was administered to consecutive admissions as part of an investigation into the treatment of alcoholics in this region [29]. The standard scores of these alcoholics were compared with those of 100 normal subjects from the Aberdeen area described by McAllister [30]. The alcoholics differed from them at the 0.1 per cent level in being emotionally unstable as opposed to mature or calm (low score on factor C); more casual or undependable as opposed to conscientious (low score on factor G), more shy (a low H score), more unrealistic or eccentric as opposed to practical (high M score), more insecure or guilt prone (high 0 score), and more tense (high 44 score). Despite the cultural differences which one would expect to influence the normal scores from North-East Scotland as opposed to the American norms, the Scottish alcoholic group also differed significantly from Cattell’s norms in all the factors mentioned above except factor M. Walton [31] described his findings using the 16 PF on a group of Although differing from our group for some of the factors 38 Edinburgh alcoholics. they did not differ for any of the factors already mentioned. It would be mistaken to jump to the conclusion that a profile typical of alcoholism had been demonstrated. McAllister [30] has shown that a group of neurotics from North-East Scotland also differed significantly from his normal group in exactly the same direction as our alcoholics for factors C, G, 0 and Q4 and his group of patients with manic depressive illness and paranoid states differed in the same way for factor M. The only factor on which none of his patient groups differed from his
292
C. MCCANCE
norms and on which our alcoholics did differ, was for factor H, the factor which suggested that the alcoholics were unusually shy. It might be concluded that the personality profiles of developed alcoholics differ significantly in a number of respects from normals but not from many other psychiatric patients, particularly neurotics and that a specific genetic factor certainly does not exert a sufficient effect to make personality irrelevant. It might, however, dispose some neurotics to solve their problems through drink. THE
ENVIRONMENT
IN
LATER
LIFE
Social and demographic data about a cohort of 194 alcoholics from North-East Scotland were gathered in connection with the treatment study already mentioned [26]. The Aberdeen case register was searched by computer to find a patient with any psychiatric diagnosis other than alcoholism, to match each individual in the cohort of alcoholics for sex, age and place of residence. This control group of patients was compared with the alcoholic patients for various social data which are collected routinely from all patients who enter the psychiatric services [32]. It was found that there were 34 seafarers amongst the alcoholics but only 9 amongst the other patients, a difference significant at the 0.1 per cent level. This high incidence of a sea-faring occupation (especially commercial fishing) amongst our alcoholic patients might seem to show that the heavy drinking customs amongst some sections of the North-East fishing fraternity, lead some men to alcoholism. What could be more understandable than being seduced into heavy drinking with a small group of shipmates when the dangers braved together are over for a spell, with a good catch to celebrate perhaps, and a pocketful of money to spend. But assumptions of cause and effect are treacherous. Brun-Gulbrandsen [33] has shown amongst Norwegian seamen, who also drink very heavily but who differ from our group in being almost entirely mercantile mariners as opposed to fishermen, that within the group of seamen the incidence of alcohol abuse was substantially higher amongst those with a low educational level, amongst those from orphanages, foster homes or homes where the parents have died or divorced although the longer the and in those with high neuroticism scores. Furthermore, service at sea, the more frequent the abuse of alcohol for the group as a whole, those with good educational level, good home background and no neuroticisms did not contribute to this trend. Thus the background and personality factors of the individual seem to be more important than the job environment and, indeed, the finding of a correlation between alcoholism and sea-faring could be explicable on the hypothesis that potential drinkers choose such a way of life. EPILOGUE
The aetiology of alcoholism can only be seen as a complicated interaction of factors and a model which represents the main elements in this interaction has been proposed. This model may clarify the relevance of individual research contributions to the overall picture and may help to formulate hypotheses for testing by further experiment. Dalen [34] has urged for psychiatric research in general that hypotheses should be simple and easily refuted. When the overall situation is clearly not simple then it has to be broken down into simpler components. Research work on different aspects of the problem from different countries
293
Aetiological factors in alcoholism
would contribute more to a composite pool of knowledge if an operational definition of alcoholism as precise as possible were adopted internationally. The W.H.O. definition of alcoholism [35] is not suitable for scientists. A simpler description in terms of the quantity of ethanol consumed per day with an attempt also to recognise the fluctuations which occur in some styles of drinking, might be less ambiguous. SUMMARY
Alcoholism, disease or otherwise, is manifest by a behavioural complex. It is proposed that causation must be regarded as an interaction of many factors operating at different levels. The pattern and quantity of alcohol intake will be influenced by three major factors; personal factors, social factors and drug factors. The personal factors, in their turn, will have been largely determined by an interaction between the genetic deal and the childhood environment. But heavy drinking, if it has developed will itself have an effect on the personal qualities, the social circumstances and the drug effects. Three aspects of research upon possible genetic factors are reviewed; the association between alcoholism and colour blindness reported from Santiago, the association between alcoholism and the non-secretion of blood group substances found in Great Britain, and the contribution from a Finnish twin study. No final conclusions can yet be drawn from the colour vision and blood group work but it seems more likely that alcohol has caused the observed anomalies than that they mark a genotypic entity associated with a predisposition to alcoholism. The twin study suggests that genes may determine to some extent, the appetite for alcohol. Research into family size, birth order and childhood bereavement is looked at and dismissed as contributing little or nothing to clarifying the effect of early environment upon the development of alcoholism. Discussion of personal qualities is confined to a brief report on some 16 P. F. results on 123 Aberdeen alcoholics. They differed from Aberdeen controls for their scores on factors C, G, H, M, 0 and 44 but these differences were largely shared by a group of neurotics. The interplay between alcoholism and occupation is exemplified by the prevalence of alcoholism amongst seamen from the North East of Scotland. In conclusion, a plea is made for a more simple operational definition of drinking behaviour in order that individual research efforts on different aspects of the problem in different countries, might each contribute more to a composite picture. Acknowledgements-I am greatly indebted to Mr. Paul Kinnear and Mr. P. K. Ray for giving me insight into some of the technical aspects of colour vision and to Dr. John Birtchnell for allowing me to communicate some of his unpublished data*. REFERENCES 1. LESTERD. Self-selection of alcohol by animals, human variation, and the etiology of alcohohsm: a critical review. Q. J. Stud. Alcohol 27, 395 (1966). 2. EDWARDSG. The status of alcoholism as a disease. In Modern Trends in Drug Dependence and Alcoholism, (Edited by PHILLIPWNR. V.), Chap. 8. pp. 140-162. Butterworths, London (1970). 3. CRUZ-COKER. Colour-blindness and cirrhosis of the liver. Lancet 1, 1131 (1965). 4. CRUZ-COKER. and VARELAA. Colour-blindness and alcohol addiction. Lancet 2, 1348 (1965). 5. CRUZ-COKER. and VARELAA. Inheritance of alcoholism: its association with colour-blindness. Lancet 2, 1282 (1966). * Some of Dr. Birchnell’s data have now been published in Br. J. Psychiat.
116,281
(1970).
C. MCCANCE
294
6. VARELA A., RIVERA L., MARDONESJ. and CRUZ-COKE R. Color vision defects in non-alcoholic relatives of alcoholic patients. Br. J. Addict. 64, 67 (1969). I. GORRELLG. J. A study of defective vision with the Ishihara test plates. Ann. Hum. Genet. 31,
39 (1967). 8. GORRELLG. J. Inheritance of alcoholism. Lancet 1, 274 (1967). 9. THULINEH. C. Inheritance of alcoholism. Lancet 1, 274 (1967). 10. SARAUX H., LABET R. and BIAIS B. Aspects actuels de la n&rite optique de l’ethylique. Annls Oculist. 199, 943 (1966). Vol. 4. 11. DUKE-ELDER S. The physiology of the eye and of vision. System of Ophthalmology. uu. 635-642. Henrv Kimuton. London (1968). of ihe eye. pp. 221-222. Charles C. Thomas, Springfield, Ill. (1962). 12. GRANT W. M. To&ologi of diabetics. Master of Science thesis, Edinburgh 13. KINNEAR P. R. The colour discrimination
University (1965). 14. CAMPS F. E. and DODD B. E. Increase in the incidence of non-secretors of ABH blood group substances among alcoholic patients Br. Med. J. 1, 30 (1967). 1.5. CAMPS F. E.. DODD B. E. and LINCOLNP. J. The frequencies of secretors and non-secretors of ABH blood group substances among 1000 alcoholic patients. Br. Med. J. 4, 457 (1969). 16. NORDMO S. H. Blood groups in schizophrenia, alcoholism, and mental deficiency. Am. J. Psychiat. 116,460 (1959). study on 17. PARTANENJ., BRUUN K. and MARKKANENT. Inheritance of drinking behaviour-a intellipence. oersonalitv, and use of alcohol of adult twins. The Finnish Foundation for Alcohol
Stud&, Publication No. 14. Helsmki (1966j. 18. SMARTR. G. Alcoholism, birth order, and family size. J. Abnorm. Sot. Psycho/. 66, 17 (1963). 19. BIRTCHNELLJ. Personal communication. 20. BAKAN D. The relationship between alcoholism and birth rank. Q. Jl Stud. Alcohol 10, 434 (1949). L., VAN DEN BOSCHE. and DENHAMB. The problem of birth order and 21. ERLENMEYER-KIMLING schizophrenia: a negative conclusion. Br. J. Psychiat. 115,659 (1969). 22. PRICEJ. S. and HARE E. H. Birth order studies: some sources of bias. Br. J. Psychiat. 115,633
(1969). 23. HARE E. H. and PRICEJ. S. Birth order and family size: bias caused by changes in birth rate. Br. J. Psvchiat. 115.647 (1969). 24. HILGA& J. R. and NEWMAN M. F. Early parental deprivation in schizophrenia and alcoholism. Am. J. Orthopsychiat. 33,409 (1963). 25. HILGARD J. R. and NEWMAN M. F. Parental loss by death in childhood as an etiological factor among schizophrenic and alcoholic patients compared with a non-patient community sample. J. Nerv. Ment. Dis. 137, 14 (1963). 26. DENNEHYC. M. Childhood bereavement and psychiatric illness. Br. J. Psychiat. 112, 1049 (1966). 27. SIM S. J. Some social and personality correlates of male alcoholics in North-East Scotland. Thesis for degree of M.A. (Hons.) Psychology. Univ. of Aberdeen (1969). 28. CATTELL R. B. and STICE G. G. Handbook of the Sixteen Personality Factor Questionnaire.
Champaigne, Illinois, I.P.A.T. (1957). 29. MCCANCE C. and MCCANCE P. F. Alcoholism 30. 31. 32. 33.
34. 35.
in North-East Scotland: its treatment and outcome. Br. J. Psychiat. 115, 189 (1969). MCALLISTERJ. Foulds “Continuum of personal illness” and the 16 P.F. Br. J. Psychiat. 114, 53 (1968). WALTON H. J. Personality as a determinant of the form of alcoholism. Br. J. Psychiat. 114, 761 (1968). BALDWINJ. A., INNESG., MILLAR W. M., SHARP G. A. and DORRICOTI.N. A psychiatric case register in North-East Scotland. Br. J. Prev. Sot. Med. 19, 38 (1965). BRUN-GULBRANDSEN S. and IRGENS-JENSEN 0. Abuse of alcohol among seamen. Br. J. Addict. 62, 19 (1967). DAL~N P. Causal explanations in psychiatry: a critique of some current concepts. Br. J. Psychiat. 115, 129 (1969). WORLD HEALTH ORGANISATION.Expert Committee on Mental Health. Alcohol Sub-committee Second Report. W.H.O. Technical Report Series No. 48. (1952).