John Romano

Embryological origin for autism: Developmental anomalies of the cranial nerve motor nuclei

The underlying brain injury that leads to autism has been difficult to identify. The diagnostic criteria of the disease are not readily associated with any brain region or system, nor are they mimicked by vascular accidents, tumors, or degenerative neurological diseases occurring in adults. Fortuitously, a recent report of autism induced by thalidomide exposure provides evidence that the disease originates by an injury at the time of closure of the neural tube. The human data suggest that the initiating lesion includes the motor cranial nerve nuclei. To test this hypothesis, we first examined motor nuclei in the brainstem of a human autistic case. The autopsy brain exhibited near‐complete absence of the facial nucleus and superior olive along with shortening of the brainstem between the trapezoid body and the inferior olive. A similar deficit has been reported in Hoxa‐1 gene knockout mice in which pattern formation of the hindbrain is disrupted during neurulation. Alternatively, exposure to antimitotic agents just after neural tube closure could produce the observed pattern of deficits. Thus, the lesions observed in the autopsy case appear to match those predicted by the thalidomide cases in both time of origin and central nervous system (CNS) location. To produce similar brain lesions experimentally, we exposed rat embryos to valproic acid, a second teratogen newly linked to autism. Dams received 350 mg/kg of valproic acid (VPA) on day 11.5 (the day of neural tube closure), day 12, or day 12.5 of gestation. Each treatment significantly reduced the number of motor neurons counted in matched sections of the earliest‐forming motor nuclei (V, XII), and progressively later exposures affected the VIth and IIIrd cranial nerve nuclei. All treatments spared the facial nucleus, which forms still later. Counts from the mesencephalic nucleus of trigeminal, the dorsal motor nucleus of the vagus, and the locus ceruleus were not affected by exposure to VPA, even though these nuclei form during the period when exposure occurred. Despite its effects on the motor nuclei, valproic acid exposure did not alter the further development of the brain in any obvious way. Treated animals were robust and had no external malformations. The autopsy data and experimental data from rats confirm that CNS injuries occurring during or just after neural tube closure can lead to a selective loss of neurons derived from the basal plate of the rhombencephalon. The results add two new lines of evidence that place the initiating injury for autism around the time of neural tube closure.

Delirium, a syndrome of cerebral insufficiency☆

Abstract The thesis is presented that a derangement in the general functional metabolism of the brain underlies all instances of delirium and that this is reflected at the clinical level by a characteristic disturbance in cognitive functions and at the physiologic level by a characteristic generalized slowing of the electroencephalogram. As background for this thesis are summarized the studies of a large number of patients exhibiting delirium in the setting of a wide variety of physiologic and biochemical derangements as well as instances of delirium experimentally induced by techniques known to affect cerebral metabolism adversely. The clinical characteristics of delirium are carefully delineated and the basis established for the identification of delirium and its differentiation from other types of psychologic disturbance commonly seen in organically ill patients.

Cell counts in cerebral cortex of an autistic patient

Numbers of neurons and glia were counted in the cerebral cortex of one well-documented case of autism and two age and sexmatched controls. Areas in which cell counts were made were primary auditory cortex, Brocas speech area, and auditory association cortex. No consistent differences in cell density were found between the brains of the autistic patient and the control patients.

Twenty-five years later.

In 1954, the State of New York, during the administration of Governor Thomas E. Dewey, and with the administrative support and guidance of Newton Bigelow, the Commissioner of the Department of Mental Hygiene enacted the nations first Community Mental Health Services Act. This landmark legislation provided for the establishment of County Mental Health Boards to plan and supervise the development and operation of local mental health and mental retardation programs with state funds to match local funds. Hyman Forstenzers contribution to the drafting, enactment, and execution of this legislation is clearly evident. Following is an attempt to understand the climate of opinion which led to this legislation and subsequently, 25 years later, to its effects in the study and care of our patients and their families.

A Cumulative Register of Psychiatric Services in a Community

THIS IS THE first report of a longitudinal study of the interaction between an entire large American community and, for practical purposes, all parts of an extensive, highly developed network of psychiatric services which serve that community. The heart of the study is a register to which are reported contacts between psychiatric patients and the gamut of psychiatric services in the community. A general outline of the operation of the register will be given below under Method.* The project arose from the perception of the principal investigators that this particular community and the unusual network of psychiatric services in it offer an opportunity to collect simultaneously longitudinal data about persons with diagnosed mental disorders and similar data about the operation of a wide range of psychiatric services. In the past, longitudinal data about either psychiatric patients or psychiatric services have been limited to a particular type of patient or a particular type of service. Because of the broad scope of the reporting sources and the longitudinal design of the register, the data from

On The Teaching of Psychiatry to Medical Students: Does It Have To Get Worse Before It Gets Better?

&NA; Attention is drawn to the principal determinants of change since World War II in the teaching of psychiatry to medical students in the United States. From the outset the goals of the educational programs were addressed to all medical students, not only those who had made a career choice in psychiatry. Although there have been minor changes, the goals have stood the test of time. For several practical reasons, current examination of our existing educational programs is timely. Comments and criticisms of generations of medical students have informed us of our successes and our failures. The ambiance of the medical school as a whole as well as that of the Department of Psychiatry have contributed to a state of dysphoria academia. Several factors are cited as possible determinants of the decline in the number of medical students who choose psychiatric careers, as well as influencing the careers of physicians other than psychiatrists. The principal recommendation is to correct the deficiencies in our teaching programs.

An experiment in the teaching of obstetrics and gynecology at the graduate level: The application of clinical psychiatry in the teaching of obstetrics and gynecology

Abstract Since 1948 each Senior Assistant Resident ∗ in this Department of Obstetrics and Gynecology has voluntarily requested and participated in clinical training in psychiatry prior to assuming the duties of Chief Resident in Obstetrics-Gynecology. This has resulted in a five-year teaching experience shared by the Departments of Psychiatry and Obstetrics-Gynecology. Other teachers have expressed interest in this experience which, we believe, may be looked upon as an experiment in graduate medical education. The purpose of this communication is to record our observations so that something may be learned of their positive and negative aspects. Like most experiments, it has both answered and created questions that deal with purpose, methods, and results.