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Biomedical subjects

B Bogerts

Publications and source records attributed to B Bogerts.

At least 91 records · Page 5Linked to original sources
PubMed1994

The distribution of nitric oxide synthase immunoreactivity in the human brain.

Nitric oxide is a free radical which is produced in the brain and is thought to be the first of a new class of neural messenger molecules. It is postulated to act by inducing an increase in cyclic guanosine monophosphate levels in target cells. The neuronal isoform of nitric oxide synthase, the enzyme responsible for the calcium-dependent synthesis of nitric oxide from L-arginine, has been purified from brain homogenate. Using a specific polyclonal antibody, we have localized brain nitric oxide synthase to the cytosol of discrete neuronal subpopulations and glial elements. These include non-pyramidal cells in the cerebral cortex, pyramidal and non-pyramidal cells of the hippocampus, aspiny neurons of the corpus striatum, basket, Purkinje and granule cells in the cerebellum and neurons of various brain stem nuclei. The localization of nitric oxide-producing neurons in morphologically different and neurochemically diverse cell types suggests a widespread neuromodulatory role for nitric oxide in the central nervous system of man.

Adult↗
PubMed1994

Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.

OBJECTIVE: This study examined the pathomorphology of the caudate nuclei in first-episode schizophrenic patients with minimal previous neuroleptic exposure. METHOD: Magnetic resonance imaging (MRI) of the brain was used to examine longitudinally the caudate pathomorphology in 29 first-episode schizophrenic patients and 10 healthy comparison subjects. MRI scans were obtained after the subjects entered the study and at 18-month follow-up. The patients were treated with standardized neuroleptic regimens during the 18-month period. Volumetric assessments of the cerebral cortex, lateral ventricles, and caudate nuclei were performed on T1-weighted coronal brain sections. In addition, the patients were systematically evaluated for psychopathology at baseline and during treatment. RESULTS: Caudate volumes increased 5.7% in the patients during the 18-month treatment interval, whereas they decreased 1.6% in the comparison subjects over the same time period. Greater amounts of antipsychotic medication received by patients before the first scan and younger age at the time of the first scan were associated with larger increases in caudate volume. CONCLUSIONS: Caudate enlargement occurs early in the course of treatment in young first-episode schizophrenic patients. This may be a result of an interaction between neuroleptic treatment and the plasticity of dopaminergic neuronal systems in young patients.

Adult↗
PubMed1994

Absence of regional hemispheric volume asymmetries in first-episode schizophrenia.

OBJECTIVE: The goal of this study was to determine whether patients experiencing their first episode of schizophrenia differ from healthy subjects in regional cerebral hemispheric volumes or asymmetries. METHOD: Regional volumes corresponding to prefrontal, premotor, sensorimotor, occipitoparietal, and temporal lobes in each hemisphere were measured on contiguous coronal magnetic resonance images in 70 patients experiencing their first episode of schizophrenia and in 51 healthy comparison subjects. RESULTS: Patients did not differ from the comparison subjects in regional or total hemispheric volumes, but they had abnormal hemispheric asymmetries. Subjects in the comparison group had significant lateral asymmetries in each region: their occipitoparietal and sensorimotor regions were larger on the left, and their premotor, prefrontal, and temporal regions were larger on the right. Patients lacked lateral asymmetries and showed significantly less asymmetry than healthy subjects in occipitoparietal, premotor, and prefrontal regions. Absence of the normal asymmetry was more common among patients initially diagnosed with the undifferentiated than with the paranoid subtype of schizophrenia and was associated with more severe negative symptoms among men. Asymmetries were related to sex and handedness regardless of diagnosis; specifically, dextral men showed more asymmetry than nondextral men or dextral women. CONCLUSIONS: The absence of normal hemispheric asymmetries suggests an anomaly in the development of laterally specialized cerebral systems in schizophrenia, and this may be associated with an initial presentation of nonparanoid psychosis.

Adult↗
PubMed1994

Cerebral morphometry and clozapine treatment in schizophrenia.

Studies of brain morphology in schizophrenia may be informative about basic pathophysiologic processes, provide clinically useful indicators of treatment response, and lead to the identification of markers for selective treatment effects. This paper reviews findings from magnetic resonance imaging studies of patients with schizophrenia conducted at Hillside Hospital, with special attention to (1) findings that have helped distinguish patients who respond well to typical neuroleptics from those who have gone on to trials of clozapine, (2) the capacity of morphological measures to predict clozapine treatment response, and (3) the possibility that selective hypertrophy of striatal structure may be caused by chronic treatment with typical neuroleptics, but not by clozapine.

Atrophy↗
PubMed1993

Hippocampus-amygdala volumes and psychopathology in chronic schizophrenia.

Volumes of the mesiotemporal structures (hippocampus-amygdala complex) were measured in 19 men who were chronic multiepisode schizophrenics and 18 age-matched healthy controls using T1-weighted contiguous coronal magnetic resonance images of 3.1-mm width. Using the level of the mammillary bodies as an anatomical landmark, the whole hippocampus-amygdala complex was divided into an anterior section (mainly containing amygdaloid tissue) and a posterior section (mainly containing the hippocampal formation). Total mesiotemporal tissue volume was reduced significantly in the patient group compared to controls (-11%), with significant reductions in both left (-20%) and right (-15%) hippocampal sections. Reduced limbic tissue volume was associated with increased severity of psychopathology. Severity of positive psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] psychosis factor) was correlated significantly with right and left total mesiotemporal volumes (Spearman rho's = -0.61 p < 0.01). Negative symptom scores (BPRS anergia factor, Scale for Assessment of Negative Symptoms [SANS] global items) were not significantly correlated with any mesiotemporal tissue volumes. The data corroborate and extend previous findings of temporolimbic structure volume reduction in schizophrenia, and suggest that the positive psychotic symptoms of schizophrenia are associated with anatomic anomalies in mesiotemporal structure.

Adult↗
PubMed1993

Brain morphology, dopamine, and eye-tracking abnormalities in first-episode schizophrenia. Prevalence and clinical correlates.

OBJECTIVE: To characterize the pathophysiology of schizophrenia and to identify biologic markers in first-episode patients with no or little prior treatment exposure. DESIGN: Prospective study of an inception cohort. SETTING: Psychiatric division of an academic medical center with a suburban metropolitan catchment area. PATIENTS: 70 patients in their first episode of schizophrenia (77%) or schizoaffective disorder (23%) with no (70%) or limited prior neuroleptic exposure (30%), and 50 healthy volunteer control subjects. ASSESSMENT MEASURES: Demographic and clinical evaluations of natural history and psychopathology; methylphenidate hydrochloride and apomorphine hydrochloride stimulation tests as measures of central nervous system dopamine activity; brain magnetic resonance imaging; eye-tracking examinations. RESULTS: Preliminary analyses demonstrate that pathobiologic features previously identified in heterogeneous and primarily chronically ill patients are also present in subgroups during their first episode. These include psychotogenic response to methylphenidate (59%), abnormal growth hormone (GH) secretion (50%), abnormal brain morphology (31%), and eye-tracking dysfunction (51%). An association of pathobiologic variables with increased symptom severity and earlier age of onset was observed but not statistically significant. The strongest associations among biologic variables were for the following: GH secretion and psychotogenic response to methylphenidate, which may reflect increased dopamine agonist neural activity; decreased GH response to apomorphine and third-ventricle enlargement, which may represent a neuropathologic correlate of anterior pituitary abnormalities; and morphologic abnormalities of the medial temporal lobe and third ventricle were associated with normal eye tracking, suggesting that these pathobiologic features are mediated by distinct processes. CONCLUSIONS: These phenomena appear to be a consequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. It remains to be determined if these biologic phenomena will remain stable over time or change with disease progression. A companion article examines the clinical significance of these findings.

Adolescent↗
PubMed1993

Recent advances in the neuropathology of schizophrenia.

This article reviews some 50 neuroanatomical postmortem studies published in the last 20 years. The majority of these studies demonstrated various types of subtle anomalies in limbic structures, that is, the hippocampus, parahippocampal gyrus, entorhinal cortex, amygdala, cingulate gyrus, and septum of schizophrenia patients. A number of schizophrenic symptoms might be related to structural and functional disturbances of these brain regions. But these studies also reported subtle changes in parts of the basal ganglia, thalamus, cortex, corpus callosum, and brainstem neurotransmitter systems. Many of the studies, however, are based on small sample sizes and, therefore, must be regarded as preliminary. Cytoarchitectonic abnormalities and lack of gliosis in limbic structures as well as the absence of normal structural cerebral asymmetry in a substantial proportion of patients indicate that these structural anomalies may reflect a disorder of prenatal brain development and argue against the notion that schizophrenia is a progressive degenerative brain disorder.

Brain↗
PubMed1993

The neuropathology of schizophrenia: past and present.

Historical aspects of neuroanatomical schizophrenia research and recent findings in limbic and basal ganglia structures of schizophrenia are briefly reviewed. Then, results of volume measurements of these brain regions from 26 schizophrenics and 28 controls belonging to our new brain collection are presented. Volumes of the hippocampus, amygdala, stria terminalis and caudate were bilaterally significantly reduced, the internal pallidum showed a trend towards smaller volumes, while brain weight, putamen, nucleus accumbens and external pallidum were unchanged. The results give further evidence of subtle focal brain tissue reductions in schizophrenics. Finally, gaps in our present knowledge in the neuropathology of schizophrenia and some basic problems in this research field are discussed.

Adult↗
PubMed1992

[Morphological brain changes in senile depressions. A morphometric computed tomographic study].

The inner and outer cerebrovascular spaces visualized by CT were measured planimetrically in 34 patients (6 men, 28 women; mean age 70.7 years) with senile depression. The purpose was to ascertain whether computed tomography (CT) can detect morphological changes in the brain of patients with senile depression. Compared with a control group without evidence of neurological and psychiatric abnormalities (10 men; 33 women; mean age 70.8 years), there was an enlargement in the group with senile depression of the lateral ventricles (P less than 0.05), occipital sulci (P less than 0.05) and lateral sulci (P less than 0.01). There was no correlation with the duration of illness or the stage of depression. These findings point to the cerebral structural changes having already been present previously and argue against a progressive process of atrophy. In the case of senile psychiatric changes, cerebral morphological changes should be paid more attention, in addition to any results from research into psychosocial causes.

Aged↗
PubMed1992

Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients.

In vivo brain imaging and postmortem investigations have demonstrated structural anomalies in the brains of schizophrenic patients. However, previous studies have not established clear relationships between the characteristic symptoms of the disorder and neuropathologic changes in specific brain regions. We have obtained high-resolution magnetic resonance brain images of first-episode schizophrenic and normal control subjects and, with a computerized mensuration system, determined the volumes of the different components of the entire ventricular system. Volumes of ventricular segments were significantly larger in patients than controls (differences ranged from 17% to 40%). Temporal horn enlargement consistently demonstrated significant correlations with a broad range of schizophrenic symptoms. Our data indicate that anomalies of limbic structures in the medial temporal lobe surrounding the temporal horn play a crucial pathophysiologic role in schizophrenia.

Adolescent↗
PubMed1992

Normal eye tracking is associated with abnormal morphology of medial temporal lobe structures in schizophrenia.

Eye tracking and brain morphology assessed by magnetic resonance imaging were examined in 48 patients in their first episode of schizophrenia and in 15 normal controls. Schizophrenic patients showed higher rates of eye tracking dysfunction and more abnormal brain morphology involving the lateral ventricles, medial temporal lobe (MTL) structures and the frontal-parietal cortex than controls. Enlargement of the lateral ventricles and global rating of abnormal brain morphology were significantly more prevalent in male schizophrenics than female schizophrenics. These findings indicate that abnormalities in a variety of brain regions are present in some schizophrenics during the period shortly after the first hospitalization and could not be a function of treatment or chronic illness. We found no relation between abnormal eye tracking and any single feature of abnormal brain morphology. However, normal eye tracking was significantly associated with MTL abnormalities in schizophrenics, reflecting an inverse association between quality of eye tracking and degree of abnormality in MTL structures. These results suggest that abnormal eye tracking is not mediated by the same processes that lead to structural brain anomalies in schizophrenia.

Adolescent↗
PubMed1992

Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study.

The sylvian fissure is known to be one of the most asymmetric structures of the human brain. Sylvian fissure length was measured in post-mortem brains of 35 schizophrenic patients and 33 matched non psychiatric control subjects. The schizophrenics showed a significantly reduced length of the left sylvian fissure (-16%, p less than 0.0001) compared to the control subjects, while the right sylvian fissure length was unchanged. Sylvian fissure asymmetry (left/right ratio) was more reduced in male schizophrenics (-24%, p less than 0.001) than in female patients (-16%, p less than 0.03). This finding is consistent with several post-mortem and MRI studies showing left temporal lobe pathology in a significant proportion of patients and may indicate that schizophrenia is a disorder of early neurodevelopment causing impaired cerebral lateralization.

Adult↗
PubMed1992

Increased prevalence of the cavum septum pellucidum in magnetic resonance scans and post-mortem brains of schizophrenic patients.

A cavum septum pellucidum (CSP) has been regarded as an incidental finding of little clinical importance. However, an association between this developmental anomaly and a diagnosis of psychosis has previously been reported. We determined the prevalence of the CSP in parallel studies of brain scans obtained with magnetic resonance (MR) imaging and in the post-mortem brains of schizophrenic patients compared with normal controls. We found a significantly increased prevalence of the CSP in both the MR scans and post-mortem brains of schizophrenic patients compared with controls. In the MR study, 17 of 81 (21%) schizophrenic patients but only 1 of 46 (2%) control subjects had a CSP. In the post-mortem study, 17 of 28 (61%) schizophrenic patients and 12 of 39 (31%) normal controls had a CSP. The increased prevalence of a CSP in schizophrenic patients further indicates that anomalous development of the limbic system is an important aspect of this disorder.

Adult↗
PubMed1992

Prospective study of psychobiology in first-episode schizophrenia at Hillside Hospital.

Heterogeneity has been a consistent problem in the research and treatment of schizophrenia. Despite marked variation in the onset, phenomenology, treatment response and outcome of schizophrenic patients, our ability to identify subtypes is remarkably limited. A major problem in schizophrenia research has been the use of cross-sectional study designs and heterogeneous patient samples at different stages of the illness and who have been previously exposed to neuroleptics which have potentially confounding effects on the disease. This study intends to identify biologic correlates of the phenomenology and course of schizophrenia by using a prospective, longitudinal, repeated measures design assessing biologic and clinical parameters including measures of psychopathology, side effects, and social adjustment to examine clinical variables of treatment response, illness course, and outcome; measures of central nervous system dopamine activity and brain morphology in patients, from the onset of their illness. Patients were ascertained at hospital admission and assessed with a battery of clinical, neuropsychologic, and biologic measures before undergoing standardized treatment for the acute and maintenance phases of the illness. Upon completion, approximately 120 first-episode patients will have entered the study and will have been followed prospectively for up to 5 years and assessed at specific time intervals. Preliminary results reveal significant abnormalities in brain morphology, growth hormone secretion, eye movement function, and psychotogenic response to dopamine agonists in first-episode, treatment-naive patients which are associated with treatment response and outcome. This article describes the study's rationale, design, and methods, and a summary of the published results to date. These are discussed in terms of their significance for putative clinical subtypes and pathophysiological models of schizophrenia.

Adolescent↗
PubMed1992

Qualitative assessment of brain morphology in acute and chronic schizophrenia.

OBJECTIVE: Neuroimaging studies of brain morphology in schizophrenia have used predominantly morphometric techniques to assess brain scans. However, as currently implemented, such methods are not particularly helpful in the routine assessment of individual patients. The purpose of this study was to evaluate brain morphology seen with magnetic resonance imaging (MRI) by qualitative assessment, the most frequently used method in clinical practice for evaluating brain scans. METHOD: First-episode (N = 62) and chronic, multi-episode (N = 24) schizophrenic patients and healthy comparison subjects (N = 42) underwent MRI of the whole head in a sequence that provided 63 contiguous brain slice images. Each subject received a rating of normal, questionably abnormal, or definitely abnormal for four brain regions (lateral ventricles, third ventricle, medial temporal lobe structures, and frontal/parietal cortex) and a global rating. RESULTS: The schizophrenic patients had significantly higher global rates of abnormal morphology (first-episode group, 31%; chronic group, 42%) than the normal subjects (5%). The highest regional rates of abnormalities were seen in the lateral ventricles and the lowest in the frontal/parietal cortex. Although the chronic patients had generally higher abnormal rates than the first-episode patients, these differences were not statistically significant. The qualitative ratings of brain morphology were significantly correlated with quantitative assessments performed in separate studies. CONCLUSIONS: Despite its limits in sensitivity (and until quantitative morphometric techniques are made practical and more widely available), qualitative evaluation of MRI scans can be a useful technique in research and clinical evaluation of patients with schizophrenia.

Adolescent↗