Search PubMed⌕ Search

Biomedical subjects

R C Roberts

Publications and source records attributed to R C Roberts.

At least 19 recordsLinked to original sources
PubMed2003

Ultrastructural correlates of haloperidol-induced oral dyskinesias in rats: a study of unlabeled and enkephalin-labeled striatal terminals.

Chronic neuroleptic treatment in rats induces vacuous chewing movements (VCMs) that mimic tardive dyskinesia. Such treatment decreases overall striatal synaptic density, but rats with VCMs also have decreased density of symmetric synapses, indicating less inhibitory synaptic transmission. This study examined the striatum to determine if enkephalinergic terminals, which form symmetric synapses, are affected. All synapses combined, asymmetric and symmetric axospinous, and enkephalinergic synapses were significantly reduced in density in the haloperidol treated group as compared to controls. A loss of asymmetric axodendritic synapses, typical of excitatory thalamic inputs, was observed preferentially in the low VCM group. A loss of symmetric axodendritic synapses was observed preferentially in the high VCM group. This study indicates that a population of synapses, other than enkephalinergic ones, is preferentially lost in the high VCM group. Moreover, lack of VCMs may be due to changes in synaptic organization that are protective as well as the absence of pathologic connections.

Animals↗
PubMed2001

Increased cortical kynurenate content in schizophrenia.

BACKGROUND: Metabolites of the kynurenine pathway of tryptophan degradation may play a role in the pathogenesis of several human brain diseases. One of the key metabolites in this pathway, kynurenine, is either transaminated to form the glutamate receptor antagonist, kynurenate, or hydroxylated to 3-hydroxykynurenine, which in turn is further degraded to the excitotoxic N-methyl-D-aspartate receptor agonist quinolinate. Because a hypoglutamatergic tone may be involved in the pathophysiology of schizophrenia, it is conceivable that alterations in kynurenine pathway metabolism may play a role in the disease. METHODS: The tissue levels of kynurenine, kynurenate, and 3-hydroxykynurenine were measured in brain tissue specimens obtained from the Maryland Brain Collection. All three metabolites were determined in the same samples from three cortical brain regions (Brodmann areas 9, 10, and 19), obtained from 30 schizophrenic and 31 matched control subjects. RESULTS: Kynurenate levels were significantly increased in schizophrenic cases in Brodmann area 9 (2.9 +/- 2.2 vs. 1.9 +/- 1.3 pmol/mg protein, p <.05), but not in Brodmann areas 10 and 19. Kynurenine levels were elevated in schizophrenic cases in Brodmann areas 9 (35.2 +/- 28.0 vs. 22.4 +/- 14.3 pmol/mg protein; p <.05) and 19 (40.3 +/- 23.4 vs. 30.9 +/- 10.8; p <.05). No significant differences in 3-hydroxykynurenine content were observed between the two groups. In both groups, significant (p <.05) correlations were found in all three brain areas between kynurenine and kynurenate, but not between kynurenine and 3-hydroxykynurenine (p >.05). In rats, chronic (6-months) treatment with haloperidol did not cause an increase in kynurenate levels in the frontal cortex, indicating that the elevation observed in schizophrenia is not due to antipsychotic medication. CONCLUSIONS: The data demonstrate an impairment of brain kynurenine pathway metabolism in schizophrenia, resulting in elevated kynurenate levels and suggesting a possible concomitant reduction in glutamate receptor function.

Adult↗
PubMed2001

Gonadal steroids reduce the density of axospinous synapses in the developing rat arcuate nucleus: an electron microscopy analysis.

The developing brain is exquisitely sensitive to gonadal steroid hormones, which permanently differentiate the neural substrate during a critical developmental period. One of the more striking sexual dimorphisms in the adult rat brain is synaptic patterning in the arcuate nucleus (ARC); females have twice the number of axospinous synapses as males (Matsumoto and Arai [1980] Brain Res. 190:238-242). Previously, we have demonstrated that a similar dimorphism in spine densities on ARC dendrites is present as early as early as postnatal day 2 (PN2) in Golgi-impregnated rat brains (Mong et al. [1999] J. Neurosci. 19:1464-1472). Males have 37% fewer dendritic spines than females. Moreover, these spine densities are sensitive to changes in the hormonal milieu such that males castrated on the day of birth have a significant increase in spine density, whereas females masculinized at birth by gonadal steroid exposure have a decreased dendritic spine density. One of the limitations of the Golgi technique is the inability to confirm the presence of synapses. The current study used quantitative electron microscopy and demonstrated that testosterone exposure dramatically reduced axospinous synapses in the ARC by PN 2. Males had 54% fewer and masculinized females had 77% fewer axospinous synapses than females (P < 0.05 and P < 0.01, respectively). We previously reported that gonadal steroids induce coincident changes in neuronal and astrocyte morphology in the neonatal ARC (Mong et al., 1999), and here confirm that these changes include an altered synaptic pattern that is strikingly similar to that observed in the adult (Matsumoto and Arai, 1980).

Animals↗
PubMed2001

Effect of chronic olanzapine treatment on striatal synaptic organization.

Our previous work has shown that chronic haloperidol treatment decreases striatal symmetric synapses preferentially in rats which develop oral dyskinesias (vacuous chewing movements (VCMs)). The present experiment tests the hypothesis that olanzapine, which does not cause dyskinesia in humans or rats, would not cause the ultrastructural changes produced by haloperidol. After 6 months of treatment, VCM scores for the olanzapine group (5.1 +/- 4.5) were similar to those of controls (5.2 +/- 3.9), whereas rats in the haloperidol group were either nondyskinetic (4.3 +/- 2.2) or dyskinetic (16.9 +/- 6.7). The volume of the striatum (mm(3)), did not differ among the groups: control, 37.5 +/- 4.7; olanzapine, 36.4 +/- 4.3; haloperidol, nondyskinetic, 40.5 +/- 6.3; haloperidol, dyskinetic, 36.6 +/- 5.9. Synaptic density (per 1 microm(3)), obtained from the central region of the striatum, did not differ between the olanzapine (0.699 +/- 0.146) and control groups (0.652 +/- 0.108). The number of asymmetric synapses in the olanzapine group (0.624 +/- 0.136) was also similar to that of controls (0.550 +/- 0.090). The number of symmetric synapses in the olanzapine group (0.074 +/- 0.032) was not significantly different from that of controls (0.096 +/- 0.043). Thus, olanzapine, in contrast to haloperidol, did not produce dyskinesias or synapse loss. These results strengthen the correlation between the expression of VCMs and striatal synaptic changes and indicate that olanzapine has fewer behavioral and anatomical side effects than does haloperidol.

Animals↗
PubMed2001

Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects.

The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen-activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved in depression, we examined the activation of p44/42 MAP kinase and expression of ERK1 and ERK2 in the post-mortem brain tissue obtained from non-psychiatric control subjects (n = 11) and age- and the post-mortem interval-matched depressed suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9 and 10) and the hippocampus of depressed suicide subjects without any change in the cerebellum. This decrease was associated with a decrease in mRNA and protein levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase (MKP)2, a 'dual function' ERK1/2 phosphatase, was increased in the prefrontal cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less activated in the post-mortem brain of depressed suicide subjects and this may be because of reduced expression of ERK1/2 and increased expression of MKP2. Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.

Adult↗
PubMed2000

Scopolamine impairs memory performance and reduces frontal but not parietal visual P3 amplitude.

It has been suggested that the P3 event-related potential (ERP) may mark the operation of certain working or long-term memory processes. It has also been reported that cholinergic blockade by scopolamine induces significant memory impairment and is associated with an increased latency, as well as amplitude reduction or abolition of the auditory P3, thus supporting hypothesised links between P3 and long-term memory function. An intriguing anomaly is that, while visual P3 latency is also increased by scopolamine, amplitude is not changed. The aim of this study was to make a more detailed assessment of the effects of scopolamine on the visual P3 at a drug dose known to induce memory impairment. After drug administration, memory performance was significantly impaired and visual P3 latency was significantly increased. There was little evidence of parietal P3 amplitude reduction, but frontal P3 amplitude was significantly reduced in both target and non-target conditions. These findings, when considered in the light of a more recent study of the effects of scopolamine on auditory P3, suggest that cholinergic blockade produces a common effect in both visual and auditory modalities of significant frontal P3 amplitude reduction, but no significant parietal P3 amplitude reduction. These results are consistent with the view that there are modality-independent generators of the parietal and frontal P3. The finding of drug-induced memory impairment and modulations of frontal ERP deflections is also consistent with recent evidence of a significant role for regions of the frontal lobe in encoding and retrieval of long-term memories.

Adult↗
PubMed2000

Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia.

OBJECTIVE: Multiple quantifiable biologic abnormalities have been localized to the hippocampus in schizophrenia. Alterations in glutamate-mediated transmission at N-methyl-D-aspartic acid (NMDA)-sensitive receptors in hippocampus have been implicated in the pathophysiology of the illness. The authors tested the hypothesis that glutamatergic transmission within and efferent from hippocampus is altered in schizophrenia. METHOD: The authors analyzed postmortem hippocampal tissue from individuals with schizophrenia and from healthy individuals. The tissue samples had been collected by two brain tissue banks, one in Maryland and the other in Melbourne, Australia. lonotropic receptor binding for the NMDA, kainate, and (3)H-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA) receptors was quantified by using usual radioligand techniques. In situ hybridization autoradiography was used to quantify mRNA for the NMDA receptor subunits NR1, NR2A, and NR2B. RESULTS: Ligand binding to the ionotropic glutamate receptors (NMDA, kainate, and AMPA) did not differ significantly overall or in any subregion between the schizophrenia tissue and the healthy comparison tissue. The only exception was AMPA receptor binding in hippocampal subregion CA2, which was slightly but significantly less in schizophrenia. However, the level of mRNA for the NMDA receptor subunits NR1 and NR2B was significantly different between groups; in several hippocampal subregions, the level of NR1 mRNA was lower and the level of NR2B mRNA higher in schizophrenia. CONCLUSIONS: Because the NR1 subunit of the NMDA receptor is critical to full receptor activity, a reduction of NR1 in hippocampus in schizophrenia suggests a functional impairment in glutamatergic transmission at the NMDA receptor, resulting in reduced glutamatergic transmission within and possibly efferent from the hippocampus in schizophrenia. This defect could underlie a hypoglutamatergic state in regions of limbic cortex, consistent with published results from other lines of research in schizophrenia.

Adult↗
PubMed1999

An ultrastructural analysis of tissue surrounding a microdialysis probe.

Microdialysis is a widely used in vivo sampling technique commonly used to monitor extracellular levels of a variety of molecules including neurotransmitters and metabolites. To facilitate interpretation of microdialysis results, this study critically examines changes in synaptic morphology induced by microdialysis. Tissue surrounding microdialysis probes was examined using light and electron microscopy at three distances from the probe tract. Microdialysis probes were implanted into rat striatum, and after 40 h of post-operative recovery were perfused with a modified Ringer's solution. Light microscope analysis revealed tissue disruption up to 1.4 mm from the probe site. Axonal damage indicative of non-excitotoxic insult was also seen as far away from the probe as was examined. The presence of dark-degenerating neurons was also noted and estimates of neuronal densities revealed loss up to 400 microm from the probe tract. This study, the first qualitative ultrastructural investigation of neuropil surrounding the probe site, indicated swollen processes up to 1.4 mm from the probe tract. Swollen mitochondria and bloated endoplasmic reticulum suggest intracellular chemical disruption. Tissue damage resulting in synaptic and neuronal disruption may affect neurotransmitter efflux or extracellular concentrations of metabolites.

Animals↗
PubMed1999

Mitochondrial pathology in human schizophrenic striatum: a postmortem ultrastructural study.

Studies using in vivo imaging or microscopic analysis of autopsy specimens indicate abnormalities in the striatum of schizophrenics including lower striatal metabolism, a change which can be normalized by antipsychotic medication. To investigate the possibility that abnormalities in schizophrenia brain may be due, in part, to pathology in mitochondria, organelles which generate energy, postmortem brain tissue from schizophrenic and control cases was obtained from the Maryland Brain Collection. Mitochondria in electron micrographs of striatal neuropil were counted and digitized. The caudate and the putamen of the schizophrenic subjects contained significantly (P < 0.05) fewer (a decrease of approximately 20%) mitochondrial profiles throughout the neuropil than did normal controls. The numbers of mitochondrial profiles per axon terminal appeared lower in the subset of schizophrenics off-drug as compared to either the subset of schizophrenics on-drug or to controls, suggesting that neuroleptic treatment may normalize this measure. The structural integrity of mitochondrial profiles in the schizophrenic striata was not obviously different from that of controls. Fewer mitochondrial profiles suggest decreased energy demands or diminished capacity to respond to energy requirements in the structures that contain them. These data are consistent with other studies showing decreased metabolism in the striatum of schizophrenics and may identify, in part, the anatomical basis of this deficit.

Analysis of Variance↗
PubMed1999

Interstitial cells of the white matter in the inferior parietal cortex in schizophrenia: An unbiased cell-counting study.

Previous studies have found an increased density of the interstitial cells of the white matter (ICWMs) in the frontal and temporal cortex in schizophrenia. Some data suggested this abnormality was restricted to a subgroup of patients, whose clinical features were consistent with the presence of the deficit syndrome. Clinical studies suggest deficit features are due to an abnormality in a cortical-subcortical circuit that includes dorsolateral prefrontal and inferior parietal cortex. We compared the density of ICWMs labeled for MAP2 immunoreactivity in Brodmann area 39 (inferior parietal cortex) from nine schizophrenia subjects (three deficit and six nondeficit) and nine matched controls using an unbiased cell-counting technique. The density of ICWMs was significantly greater in the deficit syndrome subjects compared to the nondeficit schizophrenia group (respective means +/- SEM, 0.22 +/- 0.04, and 0. 13 +/- 0.02; P < 0.05). The density of ICWMs in the deficit group was also significantly greater (P < 0.05) than that of the control group (0.09 +/- 0.02), but the nondeficit and control groups were not significantly different. These findings 1) confirm that an abnormal placement of neurons in the white matter is found in schizophrenia, 2) provide evidence for a microscopic anatomical abnormality in the inferior parietal cortex, and 3) suggest the ICWM abnormality may be confined to deficit patients.

Adult↗
PubMed1999

Mechanisms underlying attentional set-shifting in Parkinson's disease.

Patients with Parkinson's disease (PD) show impairments on tasks that require them to switch attention between two perceptual dimensions (extradimensional (ED) shifting). It has been suggested that ED shifting deficits can be caused by two separate mechanisms, 'learned irrelevance' and 'perseveration'. This study set out to test the hypothesis that enhanced learned irrelevance is present in medicated patients with PD. An enhancement of learned irrelevance in PD patients should result in increased errors on a 'deficit' shift relative to controls and decreased errors on an 'improvement' shift. A similar pair of deficit and improvement shifts were used to detect possible enhanced perseveration in patients. Instead of showing the predicted patterns of deficit and improvement, patients displayed a consistent deficit on those shifts that required that they switch their attention to a different dimension (ED shifts). In contrast, patients were not impaired on shifts that required no such shift of attention (intradimensional shifts). Although there was an increase in errors at the learned irrelevance deficit shift, a similar increase at the learned irrelevance improvement shift shows that enhanced learned irrelevance is not responsible for either of these results. Patients were no more distractible than controls, but displayed increased 'loss of set' as measured by errors generated after a rule was learned. These results point to the existence of exaggerated, rigid selective attention in patients with PD rather than a breakdown in the ability to selectively attend. There was no evidence for the existence of enhanced learned irrelevance in the patients.

Aged↗
PubMed1999

Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects.

OBJECTIVE: The enzyme phosphoinositide-specific phospholipase C (PI-PLC) is a component of the phosphoinositide signal transduction system. Other components of this system have been found to be abnormal in adults and adolescents who have committed suicide, and so the authors examined whether PI-PLC activity and protein expression of PLC isozymes are abnormal in postmortem brains of teenage suicide subjects. METHOD: PI-PLC activity and protein expression of the PLC beta1, delta1, and gamma1 isozymes were examined in Brodmann's areas 8 and 9 of postmortem brains obtained from 18 teenage suicide subjects and 18 matched comparison subjects. PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique. RESULTS: Compared with the normal subjects, the teenage suicide subjects had significantly lower PI-PLC activity and immunolabeling of the specific PLC beta1 isozyme in both membrane and cytosol fractions of Brodmann's areas 8 and 9 combined (prefrontal cortex). There was also a significant correlation between PI-PLC activity and protein levels of the PLC beta1 isozyme in the brains of the teenage suicide subjects. There was no significant difference in PI-PLC activity or level of PLC beta1 protein between the suicide subjects with a history of mental disorders and those with no history of mental disorders; however, both groups had significantly lower PI-PLC activity and expression of PLC beta1 protein than the normal subjects. CONCLUSIONS: Low PI-PLC activity and expressed levels of the PLC beta1 isozyme in postmortem brains of suicide subjects may have clinical relevance in the pathophysiology of suicidal behavior.

Adolescent↗
PubMed1998

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 microm) and intervaricose segments (0.2-0.3 microm) 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 microm) 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 ofTH 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.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

[3H]Neurotensin receptor densities in human postmortem brain tissue obtained from normal and schizophrenic persons. An autoradiographic study.

[3H]Neurotensin binding and autoradiographic techniques were used to determine the distribution and density of neurotensin receptors in normal and schizophrenic postmortem brain tissue. Coronal hemi-brain blocks of tissue were cut at the level of the caudate and hippocampus from frozen brain tissue obtained from normal individuals with no known psychiatric or neurologic illnesses and from schizophrenic subjects off- or on-antipsychotic drugs at the time of death. Each hemi-block was further divided, sectioned, thaw mounted on to slides, incubated with [3H]neurotensin and apposed to film. Digitized images were analyzed for binding densities. Areas of intense binding include the substantia nigra, the entorhinal cortex, superficial layers of the cingulate, middle frontal, and insular cortices; and with moderate binding in nucleus accumbens, and caudate. Schizophrenic patients off- (3 months or more) or on-antipsychotic drugs at the time of death were tested; all patients showed a reduced level of neurotensin receptors in the caudate (68% of normals), cingulate (34%) and prefrontal cortices (25%).

Adult↗
PubMed1998

Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: a [3H]NGD-94-1 study.

Using an indirect subtraction binding technique and human postmortem tissue, several laboratories reported finding increases in dopamine D4 receptors in caudate nuclei of schizophrenic patients, although others have not replicated these findings. NGD-94-1 is a selective D4 antagonist with low affinity for the D2 and D3 receptors. [3H]NGD-94-1 has been used in this study to directly determine the density of D4 receptors in normals (n = 13) and schizophrenic subjects (n = 7) off antipsychotic drugs for at least 3 months prior to death, or on antipsychotic (n = 7) drugs at the time of death. Human postmortem coronal brain sections were incubated with [3H]NGD-94-1 and autoradiograms developed; and binding in pertinent regions was quantified. In normals, the highest density of [3H]NGD-94-1 binding was in the hippocampus (68 fmol mg(-1), temporal (33), insular (30), and entorhinal cortices (24.9). Significant increases in [3H]NGD-94-1 density in schizophrenics (n = 14) vs normals (n = 13) were observed in the entorhinal cortex (46%) at both low and high magnifications. The increases observed in the schizophrenics were found in both schizophrenics off antipsychotic drugs for at least 3 months prior to death and those on antipsychotic drugs at the time of death. Thus, the changes may be disease-related and not a consequence of pharmacological treatment. No significant differences were found between the two schizophrenic groups in any brain area studied.

Adult↗
PubMed1997

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 (Brodmann's 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.

Adult↗