GENETIC PROBLEMS IN PSYCHIATRY .sx And their Solution by the Study of Twins By AUBREY J. LEWIS , M.R.C.P. .sx GENETICS and psychiatry have this in common , that they are old in so far as speculations and empirical practice go , but very young as sciences , and still under suspicion by their elders of being apt to romp and run wild on occasion .sx These are clearly grounds for friendship between them .sx But the respects in which they differ are significant :sx genetics would be precise , standing by " actual measurement and the Rule of Three " ; in psychiatry , on the other hand , the material of observation is fluid , not clear cut , and measurement is seldom attainable .sx I propose to consider briefly the peculiar difficulties which arise when these two are mated , or perhaps , in franker expression of my own attitude , I should say when genetics becomes the handmaid of psychiatry .sx For it is the problems of psychiatry with which I am concerned , and they are for present purposes twofold to determine what are the individual mental disorders , and how these are transmitted .sx For the latter end , genetic study is indispensable ; for the former it is of almost unexpected value .sx It might be said that the psychiatrist ought to know his own business well enough by now to have found out what the mental disorders are .sx This is a matter presently to be discussed , but I would say here that geneticists and others often assume that the diagnosis ` manic-depressive insanity,' or ` dementia praecox,' or ` hysteria,' or ` melancholia ' is as definite and trustworthy as one of ` diabetes mellitus ' or ` typhoid fever .sx ' It is not so .sx These psychiatric terms represent different sorts of diagnosis and a considerable diversity of opinion as to names and categories .sx In general medicine diagnosis and the delimitation of diseases depend on the recognition of more or less characteristic structural changes , predominant causal agents , or definite quantitative or qualitative variation of function ; normal function , which is usually average range of function , and normal structure are known , and deviations can be recognized for the most part beyond dispute ; causal agents likewise are known and detectable .sx But in psychiatry the range of the so-called normal is uncertain ; and sharp differences in kind between the actual morbid phenomena are often hard to establish ; whether a given feature is to be called a delusion , a hallucination or an obsession , may at times be a matter of terminology , to be settled only by some arbitrary standard or definition of very limited validity .sx To the much greater difficulties in the matter of actual disease-groupings , syndromes , and symptom-complexes , I shall come in a moment .sx Before starting any genetic studies , one assumes that the general principles obtained through the work of Mendel and later investigators dealing with physical structures and functions , will be valid in the particular field one is concerned with , that is , of mental " structures , " or " concepts , " and functions .sx One would need then first of all to consider how far the inheritance of mental characters has a somatic basis , such as may be found or assumed in other subjects of genetic study .sx But this is a problem which in a sense may be said not to exist , for the separation of ` mental ' from ` physical ' is generally repudiated in psychiatric epistemology , as is , for example , the false contrast between ` organic ' and ` functional ' disorders .sx For the psychiatrist or as he may properly be called , the psychobiologist it is the whole man , the organism , integrated at a conscious level , that is the living unit , reacting to situations , if you like , by means of ` physical ' and ` mental ' functions which are ` abstractions in themselves .sx and in their components ' or morphological representations ; the heart and lungs being no more actual entities permitting of independent consideration than the affects or the memory .sx In psychiatry , therefore , one is considering functions of the total person , which is more than the sum of the functions of individual parts , detached or isolated for purposes of study .sx So when the inheritance of mental disorder is spoken of , one is concerned primarily with the type or mode of reaction of the whole organism , not with the abstracted ` physical ' or ` mental ' changes .sx As a matter of convenience and to establish constant relationships , rather than by way of looking into a crux , one makes the artificial distinction between physical and mental and considers systems and functions separately .sx RELATION OF BRAIN AND MIND .sx What then are the physical correlates of mental activity ?sx The relation of the brain to mental disorders was recognized by Galen ; it was made into a famous sentence by Griesinger :sx " Geisteskrankheiten sind Gehirnkrankheiten " ; and it has been greatly furthered by recent researches , as those of the Vogts , von Economo , Elliot Smith , Monakow , and many more .sx Less clear relations exist between the working of the great systems , the metabolism , the vegetative-endocrine apparatus , and the mental state the relations are much less precise and certain than some loud talkers assert .sx But there is , it is clear , a co-ordination of psychic part-functions with definite somatic i.e. physical changes , although one can by no means explain the former by the latter .sx The co-ordination speaks for the applicability to psychic characters of genetic principles ascertained by the investigation of physical characters .sx It might be supposed , then , that the best plan would be to establish the regular relationships between somatic and psychic , and thereafter to use the somatic features as the more suitable material for genetic study , since psychic characters are so difficult todefine , measure , or describe :sx slippery customers , in short .sx Gall's Phrenology was an essay in this direction ; the work of Lava-ter and Carus likewise ; Mott concluded that a general abiotrophy , manifest in the gonads and the brain , was the central feature in dementia praecox ; and in our own times Kretschmer has given a fillip to all such studies , through his well-known attempts to find mathematical correlations between psychic and somatic structure .sx Against his conclusions and his methods very weighty objections have been urged , but even though his findings were just and sound , they would tell us only in what bodily types mental disorder of a given kind may be expected , should mental disorder occur in them at all :sx these bodily types are found also widely spread in the average population .sx It is fairly widely held that temperament is dependent on the humours , as Hippocrates supposed , and that the endocrine secretions , and even more the mid-brain and the brain-stem , are the chief material substrate for affective and conative changes .sx But any close correlation has so far proved impossible of demonstration , and although the totality of the psycho-physical constitution , integrated , with consciousness , may be taken for granted , we do not know enough of its working to use its exclusively somatic manifestations as material for gene-tic studies .sx So it becomes a question of examining the ` psychic ' phenomena of ` mental ' disorders .sx But the difficulties here , as we have already partly seen , are of a kind seldom met in somatic disorders .sx TYPES OF MENTAL DISORDER .sx In the early years of this century the great , one might say paramount , influence of Kraepelin had resulted in a systematized descriptive psychiatry , in which diseases i.e. nosological entities were separated off on grounds of etiology , course , outcome , and occasionally also of structural pathology .sx Nowadays it is very different .sx Not only have the great groups , such as Dementia Praecox and Manic-depressive Insanity , altered their boundaries and inci- .sx dentally their names , but their real existence as clinical entities is disputed .sx The prevailing point of view has become biological , with a strong teleological bias .sx Mental disorders are considered as types of reaction , complexes of attempts at adaptation along special lines .sx Certain commonly occurring types are grouped together in such broad categories as ` schizophrenia,' affective psychosis,' and the like ; but fluid transitions to the normal and intermixtures between the types comprehended in these categories are the rule .sx This conception of mental disorder has pragmatic value , since it permits of more adequate study of the individual illness , and conclusions as to its outcome , than did the earlier rigid system .sx But for genetic purposes it presents singular problems .sx There is no common morphological basis or concomitant for these reaction-types ; the chief effective causes of them are in doubt :sx it is indeed a commonplace of psychopathology that for almost any group of clinical features , a number of indispensable preceding happenings or ` causes ' may be assumed .sx No doubt this is true of general medicine also :sx not all those exposed to tubercle bacilli respond with tubercle formation in their tissues , nor if it occurs do the formation and development of the tubercles go on in the same way in different people .sx But in most ` mental ' disorders one has nothing so constant as the tubercle bacillus to deter-mine the essence , and incidentally the limits , of the particular reaction :sx there is no indispensable morbific agent , no main factor .sx Into the very pertinent disputes about the disease-concept in general , and especially in psychiatry , this is not the place to enter .sx Briefly we may say that the re-action types are by no means unitary diseases but are very useful provisional fictions , ` as if ' constructions , with which one must work .sx So far three difficulties have become apparent :sx ( 1 ) there is no constant recognizable relation between mental change and bodily structure ; ( 2 ) there are no unitary diseases ; and ( 3 ) there is not yet unanimity as to what shall be comprehended within the pro-visional ` symptom-complexes ' or ` types of reaction .sx ' Of what , then , is one to deter-mine the inheritance ?sx Some answer to this problem is to be found in that method of analyzing a mental disorder which seeks to distinguish ` pathogenic ' from ` pathoplastic ' influences .sx The latter i.e. pathoplastic may be held accountable for all sorts of individual variations from the fundamental picture , variations which are the product of special conditions of personality and environment .sx It is not to be sup-posed that a sharp distinction in this sense is always possible , but the more thorough one's inquiry , the better does one succeed in separating the superstructure from the fundamental disorder , or , to vary the metaphor for the better , in stripping the skin and other tissues from the skeleton .sx Very often it is a matter of distinguishing between the content of the psychosis and its form .sx By this means a better conception has been reached of what constitute the great endogenous types of reaction , which chiefly occupy the attention of the psychiatrist :sx the problems of the exogenous types are of a somewhat different order .sx One will therefore first seek to determine the inheritance of the fundamental disorder , stripped of pathoplastic features ; later one will consider the personality , or , more broadly , the inheritance of the ` normal ' psychic characters a very difficult task in which studies have not so far been particularly happy .sx THE STUDY OF TWINS .sx These are by no means all the problems , nor is it my intention here to describe the extraordinary successes that have been obtained , in spite of the difficulties .sx I pro-pose to go on to consider one limited branch of genetic study in which I am particularly interested .sx I mean the study of twins .sx Twins who are the outcome of two fertilized ova are in their predispositions and similarity to one another like ordinary brothers and sisters , but when questions of the development of some illness arise , they are of value since they usually grow up in .sx much the same external conditions .sx Differences between them may therefore be ascribed in the main to different inherited tendencies .sx If uni-ovular twins , on the other hand , are different , one accounts for it by dissimilar environmental influences that is , if uni-ovular twins are really identical in their inherited tendencies .sx As to this there is dispute , but I think that one may say that most of the evidence is in favour of it .sx It is not to be supposed , of course , that even if this be accepted , uni-ovular twins will be the same at birth :sx intra-uterine influences have been operative , there is often a sort of life and death struggle between them , and at birth it is quite common for the difference in weight and length between uni-ovular twins to be greater than between binovular ones .sx Such differences usually disappear as the children grow , and in many cases the twins become almost indistinguishable .sx