The Testes.—Sixty-five pairs of testes, all, save one, from psychotic persons, were studied objectively without previous knowledge of the clinical or necropsy findings. Twenty-four were anatomically senile; 24 middle-aged; 13 young, while 4 were undeveloped. Two types of fibrosis were recognized: (1) extra-tubular (34 cases), generally associated with inflammatory processes, in 16 cases with tuberculosis of the other organs, in 3 with lues, and in the other cases with other chronic diseases; ( 2) intra-tubular fibrosis (32 cases), constant in all testes of the anatomically senile group, or associated with extra-tubular fibrosis. Spermatogenesis as gauged by the abundance of germinal cells and their mitotic activity was diminished in the presence of such factors as age, infectious disease, toxæmia, failure of development. Acute changes in the germinal epithelium were associated with terminal conditions. Interstitial gland cells were fewer, smaller, and more pigmented in the older than in the younger cases. One case (dementia præcox) had a remarkably large number of them; another case (dementia præcox) had none in one atrophied testis. In general paralysis (10 cases), 5 cases showed extra-tubular fibrosis; 2 of these (the most severely affected) were from cases with tuberculosis as well. In 2 cases of cerebral syphilis, a similar fibrous inflammatory change was found. The testes in the senile psychosis group (8 cases), when tuberculosis was not present (in 6 cases) showed the maximum of the changes natural to old age: small tubules, extreme reduction in spermatogenesis, thin acellular, extra-tubular tissue, and anuclear vessels; in the 2 cases with tuberculosis, marked cellular proliferation in the vessels and extra-tubular connective tissue. In the arteriosclerotic group (7 cases), 2 showed patchy, extra-tubular fibrosis in the neighborhood of sclerotic vessels, 1 with tuberculosis showed marked extra-tubular fibrosis, the others only senile changes.In dementia præcox (16 unquestioned, 2 doubtful cases), extra-tubular fibrosis occurred in 9 cases—7 with tuberculosis, 1 with cancer and a history of gonorrhea, one with the cause undetermined. Of the remaining 9, 2 showed real gonadal insufficiency, anatomically and functionally; 5 (59 to 72 years of age at death) in spite of long duration of psychosis, showed remarkably active spermatogenesis; 1 case (age 48, duration of psychosis 25 years) showed no reduction in spermatogenesis; and 1 case (age 36, duration of psychosis 8 years) showed diminution in spermatogenesis, no fibrosis, but an inflammatory exudate (pneumonia?). In dementia præcox, the duration of the psychosis was found to have no relation to the severity of the changes in the testes, which were more dependent on intercurrent factors. It was shown that Mott and his co-workers as well as Lewis were working with material similar to ours except in point of age, and though our findings to a certain extent were similar to theirs, we could not agree to their interpretations: the findings were not regular, not peculiar to dementia præcox; moreover, these workers did not sufficiently appreciate the role of tuberculosis and other chronic disease. The excellent condition of old testes from dementia præcox cases of long standing was a conspicuous fact that could not be accounted for if the theories of the London workers be accepetd. We could not support Mott's observation of minute changes in the spermatozoon head as peculiar to dementia præcox. Lewis' differentiation of the paranoid from the other forms of dementia præcox groups, as regards the testes seems to us untenable. A comparison of our material, with that studied by Morse and others proved corroborative of our conclusions. It seemed that our material, as well as the material of the investigators quoted, did not afford any definite conclusions as to the relation of psychosis and testicular change.Among the remaining diagnostic groups, one case of pituitary tumor had undescended testes. The cases in these groups, 1 of delirium (due to cancer), 7 cases of miscellaneous organic brain disease, 2 of epilepsy, 1 of involution melancholia, 2 of a paranoic condition, 1 of mental deficiency, 1 accident case showed changes attributable to intercurrent tuberculosis or other chronic and sub-chonic diseases comparable in every respect to the changes shown in the preceding groups when these factors were present.Ovaries.—The ovaries from 43 cases were studied in the same way. These fell into three anatomical age groups: 20 into the senile, 14 into the middle-aged, and 9 into the young group. One case, pellagra, with senile ovaries, was only 53 at death, but had had a premature menopause at 32. Relative reduction in the ovum producing function was found in a variety of diagnostic groups and was considered secondary to complicating disease. Chromatin deficiency as described by Mott for dementia præcox was not limited to any group in our material. Atretic follicles were common and not limited to any group. The fibrous tufts and persistent corpora fibrosa of Poetzl and Wagner were found to be non-specific and without relation to any diagnostic group. Follicular cysts were found in a variety of diagnostic groups. A cholesteatoma and a papillary cystadenoma were found in two different cases of paranoid dementia præcox. The most important pathological finding, a patchy fibrosis with thickening of the blood vessels and, sometimes, a lymphoid exudate, occurred in 14 cases of the series: in 6 cases of general paralysis, in 1 of cerebral syphilis, in 4 of dementia præcox with tuberculosis, in 1 of pellagra, in 1 of manic-depressive psychosis with chronic pelvic disease. This fibrosis seemed to be related to syphilis, tuberculosis, or pelvic disease; its incidence in general paralysis was striking. The possibility that it represents a gonorrhœal oöphoritis is not to be ruled out, but in general paralysis at any rate, the presence of a similar process in internal organs such as the adrenal glands strongly suggests a syphilitic basis. Ovaries from cases of senile psychosis, unlike the testes of the same group, did not show an exaggerated senility. In two cases of this group, in one ovary of each case, an island of interstitial gland cells, closely resembling the cells of the same name in the testes was found in the region of the hilum.The Thyroid.—This organ was studied in 109 cases. Five types of alveoli were recognized: (1) a "normal" type, (2) a colloid type, (3) an exophthalmoid type, (4) a senile type, and (5) a fœtal type, this latter occurring only in so-called fcetal adenomata. A marked variation in the type of alveoli from section to section, and even from field to field in the same section, was noted, and a correlation between interalveolar fibrosis and colloid and senile alveoli, irrespective of the source of the fibrosis or the diagnostic grouping of the case. Ninety of the 109 thyroids showed a fibrosis; 70 of these were from cases over 50 years of age; in the 20 young cases, complicating somatic disease (tuberculosis, syphilis, etc.) seemed to be the chief determining factor. Lymphoid exudates were found in i6 cases among the 90 fibrous ones, associated with various somatic diseases in cases with a variety of psychiatric diagnoses. Swelling occurred in 9 cases with different somatic and psychiatric conditions. In 3 cases small areas of exophthalmoid alveoli were discovered: 1 case of senile psychosis, 1 of arteriosclerotic psychoseis, 1 of dementia præcox. One pellagrin with a previous hyperthyroidism showed numerous exophthalmoid alveoli. Two fcrtal adenomata were seen, one in a case of dementia præcox, one in a case of involution melancholia. There was no finding which could be considered specifically characteristic of any of the psychiatric groups: the ubiquity of fibrosis could have obscured any such specific characteristic if it was present.The Hypophysis.—This organ was studied in 105 cases. Large hypophyses were found in 1 case of general paralysis, 1 of dementia præcox, 1 of involution melancholia, 1 of febrile delirium, and 2 cases of brain tumor. One small chromophobe adenoma was found in the case of dementia præcox with large hypophysis; a similar tumor, about which there might be some question of histologic diagnosis was found in a senile case. Both patients were of the hypogenital type. Fluid was found in 4 cases, miliary abscesses in 1 case, thrombosis in 1 case. Unusually marked acidophilia was found in 9 cases, 2 of them paretic cases, and 7 being in advanced years. Unusually marked basophilia was found in 5 cases. There was no correlation between these staining reactions and the psychiatric groupings. Fibrosis occurred in 67 of the 105 glands, in 6 cases being associated with a marked lymphoid exudate. These 6 cases were: 2 cases of general paralysis; 1 of syphilitic meningitis; 1 of tuberculous meningitis; 2 of dementia præcox with tuberculosis. We could, outside of the inflammatory changes in the syphilitic cases, find no correlation between the hypophyseal findings and the psychiatric diagnosis. In our dementia præcox material, we could not corroborate Mott and Robertson's claims of chromatin deficiency in the anterior lobe cells, or Lewis' claims of "localized adenoniatous response."The Adrenals.—The adrenals were studied in 112 cases. In 73 they had been weighed. The weight seemed to bear no relation to the psychiatric diagnosis. In 7 cases where the weight of the right and left glands differed markedly, there was no correlation of anatomic and psychiatric findings. The cortex was thick in 9 cases, thin in 14, again apparently not correlated with the psychiatric grouping. Fibrosis occurred in 63 of the 112 cases—in 49 of these, the age of death was over 50. Of the 14 fibrous cases where the age at death was below 50, 7 were from cases of general paralysis. In 15 of the fibrous cases, tuberculosis was the cause of death, and in the adrenals of 2 of these cases, miliary tubercles were found. Fibrosis was thus correlated chiefly with syphilis, age and tuberculosis. Lymphocytes were found in 53 of the fibrous cases, and in 15 without fibrosis. They were either part of a true inflammatory process, or served as scavenger cells in old cases with local arteriosclerosis. Lipoid was absent from the cortex in only 3 cases. Its quantitative reduction or increase could not with certainty be established in the other cases. Thrombosis occurred in one case. A small adenoma of the medulla was found in one case (dementia præcox doubtful). In the general paralysis group only was there a probability of the anatomic changes being related to the psychosis. Here, 13 of the 17 cases showed a fibrosis, 12 of these and 1 non-fibrous case an exudate of lymphoid and plasma cells, and changes in the endothelium of the vessels. In no other psychiatric group was there any definite correlation possible. In the case of dementia præcox, it was impossible to follow Lewis in considering patches of fibrosis a specific finding, either in our material or in the material of this investigator. We could not substantiate the views of Mott and Hutton as to a reduction in the volume of the medulla, and the nuclear changes found there, though we recognize that our methods were different than those used by the London workers.Functional-Anatomical Correlations.—Among the female cases a prematurely senile ovary was correlated with a premature menopause; hyperthyroidism with exophthalmoid areas in the thyroid. For obesity, infantile uteri, and male hair distribution we found no definite anatomic correlates. Among the male cases, we could correlate undeveloped testes with feminine hair distribution in 4 cases, with inequality in adrenal weights in 2 cases, and with large hypophyses in 2 cases. For hypertrichosis we could find no anatomic correlate.Anatomic-Psychiatric Correlations. These have been stated under the summary of the findings in the various organs. For convenience, they are here briefly repeated: In general paralysis, extra-tubular fibrosis and exudate in the testes dependent on local vascular alterations; patchy fibrosis and exudate in the ovaries; rarely, a lymphoid exudate in the hypophysis; frequently a lymphoid exudate and fibrosis in the adrenals; nothing specific or unique in the thyroid. In the cerebral syphilis group, occasionally changes such as those found in the general paralysis group. In the senile group, an exaggeration of the normal degenerative process of old age in the testes; except for arteriosclerotic changes, no constant finding in the other organs. In the arteriosclerotic psychosis group, the presence of a patchy, extra-tubular fibrosis in the testes seemed dependent on the presence of local arteriosclerosis; no special feature in the other organs; arteriosclerotic changes. In dementia præcox, the lesions described in the endocrine glands were inconstant, and those which were most common (e. g., extra-tubular fibrosis in the testes, patchy fibrosis in the ovaries) were probably due to intercurrent chronic disease. The results of our study have been discussed at length in the summaries of the various organs. In the brain tumor group, large hypophyses seemed to the rule. The other psychiatric groups represented in our material contained too few examples to allow of any anatomic psychiatric correlation. However, certain cases with deliria or other psychoses with organic brain disease served very well to "control" our findings in respect to the effect of chronic disease, especially tuberculosis, on the endocrine organs.In conclusion, we should like to emphasize that we do not mean to assert the absence of any possible relation between endocrine organs and psychosis in those groups, such as dementia præcox, where our findings were essentially negative. We do, however, feel that there is no evidence in our material of such anatomic psychiatric correlation, and for the dementia præcox group in particular we believe that our material was quite comparable to the material on which several, in our opinion, untenable hypotheses have been based.It is a pleasure to express my appreciation of the assistance given me by Dr. Kirby, Director of the Psychiatric Institute and his staff. More particularly am I indebted to Dr. Charles B. Dunlap, Chief Associate in Neuropathology, whose valuable counsel has been untiringly available. The microscopic preparations were made under the direction of Miss Lillian A. Garrett, whose assistance I gratefully acknowledge. To the pathologists of the New York State Hospital System, I am under obligation not only for their assiduity in the collection of materials, but also for the good nature shown by them when not infrequently burdened with a long correspondence concerning the individual cases. The micro-photographs were made by Mr. J. Halupka.