Dennis J. Chute

Reduced striatal spine size in schizophrenia: a postmortem ultrastructural study.

NUMEROUS studies using in vivo imaging or light microscopic analysis of autopsy specimens have found abnormalities in the striatum of schizophrenics. Striatal tissue from the Maryland Brain Collection with short postmortem intervals was used in the present study. Electron micrographs of striatal neuropil were digitized to determine the area of dendritic spines. Spines were similar in size in both the caudate and the putamen in normal individuals. The spines in tissue from schizophrenics were also similar in size between these two regions. However, striatal spines in schizophrenics were ≈30% smaller than in controls (p < 0.05). Since the majority of synapses in the striatum are formed with spines, this change in the schizophrenic brain may represent aberrant synaptic conductance and/or efficacy.

Benzodiazepine receptors in the post-mortem brain of suicide victims and schizophrenic subjects

To examine the role of benzodiazepine (BZ) receptors in suicide and schizophrenia, we determined BZ receptors in post-mortem brain (Brodmanns area 10) obtained from suicide victims, schizophrenic patients, and control subjects using [3H]RO15-1788 as the radioligand. The maximum number of binding sites (Bmax) of BZ receptors in the cortex of suicide victims was significantly higher compared with controls, but this increase was mainly due to those suicide victims who died by violent means and whose Bmax was significantly higher than of those who died by non-violent means or control subjects. In schizophrenic patients, Bmax was not significantly different from that of control subjects. When the schizophrenic subjects were separated into two groups, those on neuroleptics and those off neuroleptics for at least 12 months, however, the mean Bmax of BZ receptors in the prefrontal cortex in post-mortem brain obtained from schizophrenic patients on neuroleptics was significantly lower than Bmax in drug-free schizophrenic patients or normal controls. There were no significant differences among groups in values of the apparent dissociation constant (KD) of [3H]RO15-1788 binding. These results suggest that BZ receptors are up-regulated in the cortex of suicide victims, specifically those who used violent means, and that neuroleptic treatment may result in decreased central BZ receptor binding in the cortex of schizophrenic patients. Thus, the method of suicide and previous exposure to neuroleptics should be considered in the interpretation of data on BZ receptors.

SYNAPTIC CHANGES IN THE STRIATUM OF SCHIZOPHRENIC CASES: A CONTROLLED POSTMORTEM ULTRASTRUCTURAL STUDY

Although studies indicate abnormalities in the striatum of schizophrenic people, little information exists on the synaptic changes that may be present at the ultrastructural level. Autopsy specimens of striatal tissue from people with schizophrenia, normal controls, and psychiatric controls were obtained from the Maryland Brain Collection. Several abnormalities were noted in the schizophrenic group that were not present in the normal or psychiatric controls. In schizophrenic tissue, the density and/or proportion of symmetric synaptic profiles, particularly those ending on spines, were lower in the caudate vs. the putamen, implying an imbalance in inhibitory synaptic transmission between these two structures. The density of perforated synaptic profiles, cortical afferents thought to be involved in synaptic turnover and cognition, was lower in the striatum of the schizophrenic group compared to the control groups. The density of axodendritic synaptic profiles, particularly of the asymmetric type, was decreased in the caudate, but not the putamen, of a subset of schizophrenic cases that were nondyskinetic and off drugs (NDODS). The proportion of asymmetric axospinous synaptic profiles was elevated in the caudate of the NDODS cases in comparison to normal controls. The variety of synapses affected in the schizophrenic group implies the involvement of several neuronal circuits. The alterations observed in the schizophrenic striatum were usually due to changes in the caudate, but not the putamen, which argues against drug‐related alterations. Since the striatum, particularly the caudate nucleus, is involved in cognition and emotion, these neuroanatomical changes could underlie, in part, aspects of schizophrenic psychopathology. Synapse 28:125–139, 1998.

Immunocytochemical localization of tyrosine hydroxylase in the human striatum: a postmortem ultrastructural study.

An electron microscopic evaluation of tyrosine hydroxylase (TH) immunocytochemistry was used to describe the synaptic organization of dopamine innervation of the striatum in postmortem human brain tissue. TH immunoreactivity was qualitatively and quantitatively similar in the caudate and putamen. TH immunoreactivity was present mainly in unmyelinated axons and occasionally in myelinated axons. Both TH‐immunoreactive (TH‐i) varicosities (0.75–1.5 μm) and intervaricose segments (0.2–0.3 μm) formed synapses with spines and dendrites. Most synapses formed by TH‐i profiles were symmetric axospinous (57–62%) or symmetric axodendritic (33–35%). An occasional asymmetric axodendritic or asymmetric axospinous synapse was observed. Approximately 35–50% of all symmetric axospinous and axodendritic synapses were formed by TH‐i boutons. Synapses formed by TH‐i profiles were short in length (0.226 μm) and had nonperforated postsynaptic densities. TH‐i profiles formed synapses with both the head (40%) and the neck (60%) of spines. Typically, the TH‐i bouton was apposed to both a spine and a nonlabeled terminal which formed an asymmetric synapse with that spine. Direct, nonsynaptic appositions were often seen between TH‐labeled and nonlabeled boutons forming asymmetric synapses. The general pattern of TH immunoreactivity was similar to that of other species except for the presence of TH‐i myelinated axons and the observation that the majority of TH‐i synapses were formed with spines rather than with dendritic shafts. J. Comp. Neurol. 390:52–62, 1998.

Schizophrenia and sudden death: a medical examiner case study

This study reviews the causes of sudden death of 66 schizophrenic patients who presented to the Office of the Chief Medical Examiner (OCME) for the State of Maryland over a 3-year period from 1994 through 1996. We identified an increased incidence of suicide compared with the general population of OCME cases. This observation is consistent with reports by other investigators. The majority of the deaths were the result of natural diseases, mostly atherosclerotic cardiovascular disease. Accidents, suicides, and 1 homicide were also present in this group.

Synaptic organization of the human striatum: a postmortem ultrastructural study.

The goal of this study was to characterize the synaptic organization of the normal human adult striatum for comparison with other species and with the diseased human striatum. Samples of striatal tissue from the Maryland Brain Collection obtained at autopsy with postmortem intervals of less than 4 hours were prepared for electron microscopic analysis according to standard techniques. The caudate nucleus and the putamen were similar in terms of the proportions of synaptic subtypes, the lengths of synaptic subtypes, and the area of most types of axon terminals. The proportions of major striatal synaptic subdivisions, such as axospinous synapses (83.5%) and asymmetric synapses (77.5%), were similar to that of the monkey (82% and 77%, respectively) but slightly lower than found in the rat (90% and 89%, respectively). Interestingly, the proportion of synapses with perforated postsynaptic densities (23%), a type of synapse thought to represent synaptic plasticity, was much higher in humans than in rats (5–8%). The lengths of asymmetric synapses (0.697 μm) were significantly longer than that of symmetric synapses (0.423 μm), a relationship found in other mammals. Also, the areas of terminals forming asymmetric synapses (0.707 μm2) were larger than those forming symmetric synapses (0.401 μm2), also consistent with data from other species. The length of axospinous synapses (0.656 μm) and the area of the terminals forming them (0.611 μm2) were not significantly different from the length of axodendritic synapses (0.523 μm) or the area of terminals forming them (0.602 μm2). This study is the first quantitative study on synaptic organization in human postmortem striatum. The results indicate that the synaptic organization of the human striatum is similar, but not identical, to that of other mammalian species.

Air bag-associated injury to a child in the front passenger seat.

We report the case of a 3.5-year-old front seat passenger who suffered significant head and neck injuries as a result of air bag deployment in a collision of <30 mph. These lesions included multiple abrasions of the lower half of the face, nose, forehead, and right ear, torn frenula, conjunctival petechiae, comminuted fractures of the left and right lateral frontal regions and right parietal bone, diastatic fracture of the coronal suture, subgaleal and subarachnoid hemorrhages, cortical contusions, subluxation of the atlantooccipital joint, and fracture of the C4 vertebral body. These lesions are consistent with trauma secondary to the deploying air bag and the head striking the interior of the car. The findings in this case further support the Centers for Disease Control and Prevention (CDC) guidelines of keeping children properly restrained, preferably in the back seat, or as far as possible from air bags.

Spontaneous rupture of urinary bladder associated with massive fecal impaction (fecaloma).

We report a case of sudden death due to a catastrophic spontaneous rupture of a urinary bladder associated with megacolon due to a fecal impaction (fecaloma). The massively distended rectum and sigmoid colon filled the pelvic cavity and pressed up against the posterior aspects of the uterus, vagina, and urinary bladder. This produced bladder outlet obstruction, followed by massive dilatation and rupture of the urinary bladder, bilateral hydronephrosis, and a 3.5 liter collection of urinary fluid within the abdominal cavity. Complications of chronic constipation, fecalomas, and rupture of the urinary bladder are reviewed.

Injury patterns in a plastic (AR-1) baton fatality.

Rubber and plastic bullets or batons have been used in countries outside the United States for several years. These devices were designed to inflict nonlethal force in riot control. The authors report a case of fatal injury sustained by an elderly woman struck in the chest by a plastic baton, including the circumstances surrounding this unusual incident, the autopsy findings and a review of the literature.

Angiocentric Systemic Granulomatosis

As part of a review of substance abuse deaths in Dutchess County, New York, the Dutchess County Medical Examiners Office identified 3 cases of angiocentric systemic foreign-body granulomatosis discovered at autopsy. Our investigation disclosed that in all 3 cases patients surreptitiously injected crushed oral prescription medication. Of the patients, 2 obtained intravenous access through central venous lines, the other patient was found to have injected herself intramuscularly. Autopsy demonstrated lung abnormalities due to diffuse deposits of foreign material within and around vessels, associated with foreign-body granulomatous reaction. We also identified a systemic distribution of this foreign material deposited beyond the lungs in the brain, heart, kidneys, and spleen. We present these cases along with a review of the literature of systemic embolization of foreign material in previously documented cases of deaths due to parenteral abuse of oral medications.