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explanation as to the manner in which insanity may appear in families previously free from the taint. Very frequently we find in the history of insane patients that although there may be no insanity in the family there are undoubted indications of nervous alongside of physical instability, the parental nervous defects taking the form of extreme nervousness, vagabondage, epilepsy, want of mental balance, inequality in mental development or endowment, extreme mental brilliancy in one direction associated with marked deficiency in others, the physical defects showing themselves in the form of insanity; liability to tubercular and rheumatic infections. The failure of constitutional power which allows of the invasion of the tubercle bacillus and the micrococcus rheumaticus in certain members of a family is apparently closely allied to that which favours the development of mental symptoms in others.

6. Consanguinity.—It has been strongly asserted that consanguineous marriage is a prolific source of nervous instability. There is considerable diversity of opinion on this subject; the general outcome of the investigations of many careful inquirers appears to be that the offspring of healthy cousins of a healthy stock is not more liable to nervous disease than that of unrelated parents, but that evil consequences follow where there is a strong tendency in the family to degeneration, not only in the direction of the original diathesis, but also towards instability of the nervous system. The objection to the marriage of blood relations does not arise from the bare fact of their relationship, but has its ground in the fear of their having a vicious variation of constitution, which, in their children, is prone to become intensified. There is sufficient evidence adducible to prove that close breeding is productive of degeneration; and when the multiform functions of the nervous system are taken into account, it may almost be assumed, not only a that it suffers concomitantly with other organs, but that it may also be the first to suffer independently.

7. Parental Weakness.—Of the other causes affecting the parents which appear to have an influence in engendering a predisposition to insanity in the offspring, the abuse of alcoholic stimulants and opiates, over-exertion of the mental faculties, advanced age and weak health may be cited. Great stress has been laid on the influence exercised by the first of these conditions, and many extreme statements have been made regarding it. Such statements must be accepted with reserve, for, although there is reason for attaching considerable weight to the history of ancestral intemperance as a probable causating influence, it has been generally assumed as the proved cause by those who have treated of the subject, without reference to other agencies which may have acted in common with it, or quite independently of it. However unsatisfactory from a scientific point of view it may appear, the general statement must stand that whatever tends to lower the nervous energy of a parent may modify the development of the progeny. Constitutional tendency to nervous instability once established in a family may make itself felt in various directions—epilepsy, hysteria, hypochondriasis, neuralgia, certain forms of paralysis, insanity, eccentricity. It is asserted that exceptional genius in an individual member is a phenomenal indication. Confined to the question of insanity, the morbid inheritance may manifest itself in two directions—in defective brain organization manifest from birth, or from the age at which its faculties are potential, i.e. congenital insanity; or in the neurotic diathesis, which may be present in a brain to all appearance congenitally perfect, and may present itself merely by a tendency to break down under circumstances which would not affect a person of originally healthy constitution.

8. Periodic Influence.—The evolutional periods of puberty, adolescence, utero-gestation, the climacteric period and old age exercise an effect upon the nervous system. It may be freely admitted that the nexus between physiological processes and mental disturbances is, as regards certain of the periods, obscure, and that the causal relation is dependent more on induction than on demonstration; but it may be pleaded that it is not more obscure in respect of insanity than of many other diseases. The pathological difficulty obtains mostly in the relation of the earlier evolutional periods, puberty and adolescence, to insanity; in the others a physiologico-pathological nexus may be traced; but in regard to the former there is nothing to take hold of except the purely physiological process of development of the sexual function, the expansion of the intellectual powers, and rapid increase of the bulk of the body. Although in thoroughly stable subjects due provision is made for these evolutional processes, it is not difficult to conceive that in the nervously unstable a considerable risk is run by the brain in consequence of the strain laid on it. Between the adolescent and climacteric periods the constitution of the nervous, as of the other systems, becomes established, and disturbance is not likely to occur, except from some accidental circumstances apart from evolution. In the most healthily constituted individuals the "change of life" expresses itself by some loss of vigour. The nourishing (trophesial) function becomes less active, and either various degrees of wasting occur or there is a tendency towards restitution in bulk of tissues by a less highly organized material. The most important instance of the latter tendency is fatty degeneration of muscle, to which the arterial system is very liable. In the mass of mankind those changes assume no pathological importance: the man or woman of middle life passes into advanced age without serious constitutional disturbance; on the other hand, there may be a break down of the system due to involutional changes in special organs, as, for instance, fatty degeneration of the heart. In all probability the insanity of the climacteric period may be referred to two pathological conditions: it may depend on structural changes in the brain due to fatty degeneration of its arteries and cells, or it may be a secondary result of general systemic disturbance, as indicated by cessation of menstruation in the female and possibly by some analogous modification of the sexual function in men. The senile period brings with it further reduction of formative activity; all the tissues waste, and are liable to fatty and calcareous degeneration. Here again, the arteries of the brain are very generally implicated; atheroma in some degree is almost always present, but is by no means necessarily followed by insanity.

The various and profound modifications of the system which attend the periods of utero-gestation, pregnancy and child-bearing do not leave the nervous centres unaffected. Most women are liable to slight changes of disposition and temper, morbid longings, strange likes and dislikes during pregnancy, more especially during the earlier months; but these are universally accepted as accompaniments of the condition not involving any doubts as to sanity. But there are various factors at work in the system during pregnancy which have grave influence on the nervous system, more especially in those hereditarily predisposed, and in those gravid for the first time. There is modification of direction of the blood towards a new focus, and its quality is changed, as is shown by an increase of fibrin and water and a decrease of albumen. To such physical influences are superadded the discomfort and uneasiness of the situation, mental anxiety and anticipation of danger, and in the unmarried the horror of disgrace. In the puerperal (recently delivered) woman there are to be taken into pathological account, in addition to the dangers of sepsis, the various depressing influences of child-bed, its various accidents reducing vitality, the sudden return to ordinary physiological conditions, the rapid call for a new focus of nutrition, the translation as it were of the blood supply from the uterus to the mammae—all physical influences liable to affect the brain. These influences may act independently of moral shock; but, where this is coincident, there is a condition of the nervous system unprepared to resist its action.

(b) Proximate Causes.—The proximate causes of insanity may be divided into (1) toxic agents, (2) mechanical injury to the brain, including apoplexies and tumours, and (3) arterial degeneration.

1. Toxic Agents.—The definite nature of the symptoms in the majority of the forms of acute insanity leave little reason to doubt that they result from an invasion of the system by toxins of various kinds. The symptoms referred to may be briefly indicated as follows: (i.) Pyrexia, or fever generally of an irregular type; (ii.) Hyperleucocytosis, or an increase of the white blood corpuscles, which is the chief method by which the animal organism protects itself against the noxious influence of micro-organisms and their toxins. In such cases as typhoid fever, which is caused by a bacillus, or Malta fever which is caused by a coccus, it is found that if the blood serum of the patient is mixed in vitro with a broth culture of the infecting organism in a dilution of 1 in 50, that the bacilli or the cocci, as the case may be, when examined microscopically, are seen to run into groups or clusters. The organisms are said to be agglutinated, and the substance in the serum which produces this reaction is termed an agglutinine. In many of the forms of insanity which present the symptom of hyperleucocytosis there can also be demonstrated the fact that the blood serum of the patients contains agglutinines to certain members of a group of streptococci (so called on account of their tendency to grow in the form of a chain, στρεπτός; (iii.) the rapid organic affection of the special nerve elements depending upon the virulence of the toxin, and the resistance of the individual to its influence; (iv.) the marked physical deterioration as indicated by emaciation and other changes in nutrition; (v.) the close analogy between the character of many of the mental symptoms, e.g. delirium, hallucinations or depression, and the symptoms produced artificially by the administration of certain poisonous drugs.

The toxic substances which are generally believed to be associated with the causation of mental disorders may be divided into three great classes: (a) those which arise from the morbific products of metabolism within the body itself "auto-intoxicants"; (b) those due to the invasion of the blood or tissues by micro-organisms; (c) organic or inorganic poisons introduced into the system voluntarily or accidentally.

(a) Auto-intoxication may be due to defective metabolism or to physiological instability, or to both combined. The results of defective metabolism are most clearly manifested in the mental symptoms which not infrequently accompany such diseases as gout, diabetes or obesity, all of which depend primarily upon a deficient chemical elaboration of the products of metabolism. The association of gout and rheumatism with nervous and mental diseases is historical, and the gravest forms of spinal and cerebral degeneration have been found in association with diabetes. Until the pathology of these affections is better understood we are not in a position to determine the nature of the toxins which appear to be the cause of these diseases and of their accompanying nervous