I propose in this address to call your attention to some phases of mental disorder which depend on toxæmic states These are now differentiated by the alienist, and it is only in recent times that their true nature has been unfolded. They have been long recognised as clinical features of disease, and the sources of them are as varied as are the separate toxic elements which induce them. Progress in physiological chemistry and bacteriology has now furnished us with the means to explain these conditions. The origin of these toxins is at least threefold. They may be generated in the body (auto-intoxicants), or by the malign working of microbes introduced from without, or they may arise by impregnation with organic poisons, or yet again result from the habits of alcoholism, chloralism, cocainism, and morphinism. In the majority of cases of insanity I suppose it will be conceded that there is a hereditary or inborn predisposition to the disorder, an instability or a tendency to this cerebral degeneration which may remain latent until conditions arise which are potent to elicit the breakdown. In the class of mental disorders we are now to consider there may or may not be this inherited fault of brain tissue. In many instances of toxic insanity we have to deal with persons who are already predisposed to mental instability, but in other cases a previously normal brain may be so damaged by toxic influences as to manifest aberration. We have long recognised the toxic effects on the nervous system of the altered metabolism induced by renal inadequacy in Bright's disease in the varied forms of uræmia, in that strange variety of autotoxy due to inability of the hepatic and muscular tissues to hold carbohydrate in reserve, resulting in diabetic coma, and that variety which depends on acute atrophy of the liver. We can now understand how these auto-intoxications act in disturbing the harmony of intimate brain-cell metabolism. Their effects are as certain as are those of poisons directly introduced by the mouth or under the skin. The chemical functions of the brain cell are disordered in precisely the same manner. In the ordinary practice of medicine we are familiar with states of delirium and mental aberration in the course of the various fevers and in pneumonia. Recognising these as infective disorders we now know that we are dealing with the toxic effects of invading parasites, and that amongst the manifold expressions of their presence are nervous or brain symptoms. These are frequent in pneumonia, and strangely so when the pulmonary apex is involved. The reason for this is to me inscrutable, and I can only conceive that it results from some special local nervous relations which have hitherto escaped the recognition of the physiologists. With respect both to pneumonia(1) and the various fevers, I have to add that a careful inquiry in cases where grave nervous or mental symptoms have supervened, has almost always revealed the existence of personal or family neuropathic taint. Puerperal insanity occupies precisely the same position, and inquiries in these cases show that about one half of them occur in women of neurotic or insane proclivity. Toxic influences naturally affect them more readily and with greater gravity.(2) The insanity of lactation probably owns a different cause, and may be attributed to debility and imperfect nutrition, acting probably in many cases upon an originally unstable brain. What has been termed “post-operative insanity,” due to infective influence, together with shock or exhaustion, and occurring within a few days after operation, may be similarly classified, although Mr. T. C. Dent is of the opinion that heredity of brain weakness plays but a small part in these cases, and that some of them apparently result from the influences of the anæsthetic agents employed or from iodoform impregnation.
Toxic effects of fipronil and its metabolites on PC12 cell metabolism
