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Biomedical subjects

B Bogerts

Publications and source records attributed to B Bogerts.

At least 55 records · Page 3Linked to original sources

Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients.

Noradrenergic neurons of the locus coeruleus (LC) have been implicated in the neurobiology of depression and suicidal behavior. The current postmortem study determined numbers of noradrenergic neurons by immunostaining the synthesizing enzyme tyrosine hydroxylase in the LC of 12 non-elderly depressed patients with a mood disorder as compared to 12 age- and sex-matched normal controls. Six patients were suicide victims, the other six patients died of natural causes. Non-suicidal patients had fewer neurons immunoreactive for tyrosine hydroxylase (TH-ir) than suicide victims or controls. No difference appeared between the number of TH-ir neurons in suicide patients and controls. Numbers of pigmented LC neurons were equal in patients and controls. The differences of TH-immunoreactivity could neither be attributed to drug influences nor to polarity of depressive disorder (i.e., unipolar/bipolar). Numbers of TH-ir neurons correlated positively with mean doses of tri- or tetracyclic antidepressants. Results of this study suggest a presynaptic noradrenergic deficit of the LC in depressed non-suicidal patients. Indirect evidence is provided that suicide is not related to decreased noradrenergic function and that traditional antidepressants may enhance noradrenergic activity of the LC in depressed patients.

Adult↗

Unipolar-bipolar dichotomy of mood disorders is supported by noradrenergic brainstem system morphology.

BACKGROUND: The biological basis of unipolar-bipolar dichotomy of mood disorders was investigated in this postmortem study by morphological comparison of the locus coeruleus (LC) as the main source of noradrenergic transmission in the brain. METHODS: Numbers and the rostro-caudal as well as ventro-dorsal distribution of neuromelanin-containing neurones in the LC were determined in brainstem of 12 patients with bipolar disorder (n = 6) or major depression (n = 6), and 12 normal comparison subjects. RESULTS: Bipolar patients had significantly more neurones on both sides of the LC as a whole than patients with major depression. Topographical analysis revealed that this difference was restricted to the rostral two thirds and the dorsal part of the LC, in which bipolar patients showed at least a trend to higher neurone numbers as compared to unipolar patients or to controls. LIMITATIONS: Small case numbers. CONCLUSIONS: Results suggest differences of innervation arising from the LC of bipolar patients as compared to patients with major depression. These first data of brainstem transmitter system morphology in unipolar and bipolar disorder are in line with neuroanatomical studies of other brain regions indicating a biological basis of the unipolar-bipolar dichotomy of mood disorders.

Adult↗

Cerebral volume asymmetries in schizophrenia and mood disorders: a quantitative magnetic resonance imaging study.

Multiple abnormalities of brain structure have been identified in schizophrenia using in vivo neuroimaging methods, but little is known about the diagnostic specificity of these abnormalities. In a prior study of first-episode schizophrenia we found that this group lacked the normal pattern of cerebral volume asymmetries. Data from that study were combined with data from groups of patients with more chronic schizophrenia, and with bipolar and unipolar mood disorders, to determine the specificity of this abnormality to diagnostic subgroups defined by syndromal status or chronicity. The total sample comprised 235 patients (67 healthy volunteers, 81 patients with mood disorders or schizoaffective disorders, and 87 with schizophrenia or schizophreniform disorders). Asymmetries of regional cerebral volumes were measured on coronal magnetic resonance images with 3.1-mm contiguous slices and nominal in-plane resolution of 1 mm x 1 mm. Asymmetries differed significantly across groups in the occipitoparietal, prefrontal, and temporal regions. These asymmetries, and a composite index of asymmetry across regions ('torque'), all showed the same diagnostic group effect, with the schizophrenia group showing the least normal asymmetry, the mood disorder group intermediate asymmetry, and the control group the most marked asymmetry. No other diagnostic subgroup or chronicity effects were apparent. The findings support a 'continuum' rather than a 'diagnostic specificity' hypothesis, and suggest that the reduction of normal hemispheric asymmetries may mark a neurodevelopmental risk factor for major mental illnesses, and that some syndromal characteristics may be correlated with the degree of deviation from the normal anatomic pattern.

Adolescent↗

Prefrontal enlargement of CSF spaces in agoraphobia: a qualitative CT-scan study.

1. This CT study was designed to assess brain morphology in 21 patients with agoraphobia and 21 normal control subjects matched for age and sex. 2. Internal and external CSF spaces were evaluated by qualitative assessment on a 3-point scale (normal, questionable, abnormal). 3. Patients showed bilateral enlargement of prefrontal CSF spaces (p < .05). The rating abnormal" was given in the left hemisphere to 6 (28.6%) of the patients, to 4 (19%) of the patients in the right hemisphere, but to none (0%) of the normal controls. 4. These findings suggest that alterations in brain morphology are involved in the etiology of agoraphobia.

Adult↗

Disruption of latent inhibition in rats with postnatal hippocampal lesions.

Disruption of latent inhibition has been proposed as a possible model of cognitive abnormalities that underlie positive symptoms of a schizophrenia. We tested neonatal hippocampal lesioned rats in a latent inhibition paradigm. Lesions of the ventral hippocampus were induced by bilateral injections of ibotenic acid in 7 days old rats. The behavior of lesioned rats was tested postpubertally. We found a hyperresponsiveness to dopaminergic stimulation by apomorphine in locomotion tests. Latent inhibition was tested using the acquisition of a conditioned reaction in a two-way shuttle box. Sham operated control animals showed after preexposure of the to-be-conditioned stimulus (combined tone and light stimulus) a low acquisition. Ibotenic acid lesioned animals learned the conditioned reaction with and without preexposure in the same way, indicating disturbed latent inhibition. These results demonstrate disturbances in early postnatal hippocampal lesioned rats comparable with those seen in schizophrenic patients, thus further validating this procedure as a useful animal model of some aspects of schizophrenia.

Anesthesia↗

Reduced activation and altered laterality in two neuroleptic-naive catatonic patients during a motor task in functional MRI.

BACKGROUND: Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI). METHODS: Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI). RESULTS: Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side. CONCLUSIONS: In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.

Acute Disease↗

Regional and cellular distribution of neural visinin-like protein immunoreactivities (VILIP-1 and VILIP-3) in human brain.

Neural visinin-like proteins (VILIPs) are members of the neuronal subfamily of intracellular EF-hand calcium sensor proteins termed the NCS family, which are thought to play important roles in cellular signal transduction. While numerous studies suggest a wide but uneven distribution of these proteins in rat and chicken brain, their location in, and possible significance for, the human brain, remains to be established. We used specific polyclonal antisera to map the human brain for VILIP-1 and VILIP-3 immunoreactivities. VILIP-1 was detected in cortical pyramidal cells and interneurons, septal, subthalamic and hippocampal neurons (subfields CA1 and CA4 pyramidal cells and especially hilar interneurons) as well as in cerebellar Golgi, basket, granule, stellate and dentate nucleus neurons. Purkinje cells were free of immunoreaction. VILIP-3 was more restricted in its distribution. It was identified in cerebellar Purkinje cells and a subpopulation of granule neurons. Further, neurons belonging to different nuclei of the brain stem and multiple subcortical nerve cells stained for visinin-like protein 3. A weak immunoreaction appeared in cortical and hippocampal neurons. Intracellularly the immunoreactivity appeared in the perikarya, dendrites and some axons. Sometimes, immunostaining was found in the neuropil. Glia did not express visinin-like proteins. Our findings support, from a neuroanatomical viewpoint, the idea that these calcium sensor proteins may be of relevance for neuronal signalling in the human CNS.

Animals↗

No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study.

Schizophrenia is clinically and neuropsychologically characterized by severe cognitive and functional impairment suggesting the presence of a neurodegenerative process in the brains of affected individuals. A variety of neuroanatomical changes have been described such as loss and disorientation of neurons in grey and white matter and cortical atrophy. However, the neuropathological basis for schizophrenia is still unclear. In the present study we monitored the density of GFAP-positive astrocytes in brains of 33 schizophrenic patients and 26 healthy controls. Both grey matter (entorhinal cortex and subiculum) and white matter (premotor cortex, subventricular zone of the third ventricle and next to inferior horn) structures were measured bilaterally. The overall finding was that there is no evidence for increased astrogliosis in brains of schizophrenic patients vs healthy controls. Therefore, degeneration is unlikely to be the main neuropathological mechanism in schizophrenic brains.

Astrocytes↗

Borna disease virus in human brains with a rare form of hippocampal degeneration but not in brains of patients with common neuropsychiatric disorders.

To estimate the frequency of persistent Borna disease virus (BDV) infections of the human central nervous system and to determine which neuropsychiatric disorders might be associated with this viral infection, reverse transcription-nested polymerase chain reaction was used to screen a large collection of autopsy brain samples for the presence of BDV-specific nucleic acids. The presence of BDV RNA was found in 3 brains of persons with psychiatric symptoms and prominent hippocampal degeneration previously reported to be positive by others. However, no BDV RNA was detected in 86 randomly collected brains from persons with various psychiatric disorders, including schizophrenia, affective disorders, and Alzheimer's disease, or from suicide victims or in 52 brains from healthy controls. Furthermore, no BDV-RNA was detected in 16 surgical brain samples from persons with epilepsy-associated hippocampal sclerosis. These results indicate that life-long persistent BDV infections are rare in humans and that such infections may be associated with certain forms of hippocampal degeneration.

Adult↗

Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding.

OBJECTIVES: Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam. The benzodiazepine receptor distribution was therefore investigated in akinetic catatonia with single photon emission tomography (SPECT) using iodine-123-iomazenil ((123) I Iomazenil). METHODS: Ten akinetic catatonic patients, 10 psychiatric controls (similar age, sex, medication, and underlying psychiatric diagnosis but without catatonic syndrome), and 20 healthy controls were investigated with SPECT 2 hours after injection of (123) I Iomazenil. To exclude potential effects of cerebral perfusion (r-CBF) r-CBF was additionally investigated with Tc-99mECD SPECT. RESULTS: Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls. In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia whereas in the left sensorimotor cortex no differences in r-CBF between groups were found. Catatonic motor and affective symptoms showed significant correlations (p<0.05) with benzodiazepine binding in the left sensorimotor cortex as well as with right parietal r-CBF. CONCLUSIONS: Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia. In addition to reduced GABA-A receptor density in the left sensorimotor cortex the parietal cortex seems to be involved in pathophysiology of catatonic symptoms. It is concluded that, considering results from correlation analyses, both emotional and motor symptoms in catatonia seem to be closely related to left sensorimotor and right parietal alterations.

Adult↗

Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study.

Volumes of basal ganglia in postmortem brains of 8 patients with mood disorders and 8 control subjects without neuropsychiatric disorder were determined. Morphometry of serial whole-brain sections under the control of postmortem artifacts revealed reduced volumes of the left nucleus accumbens (-32%, P = 0.01), the right and left external pallidum (-20%, P = 0.04), and the right putamen (-15%, P = 0.04) in the patient group compared with the control group. These results suggest that, in particular, the limbic loop of the basal ganglia involving the nucleus accumbens and the pallidum is affected in mood disorders.

Adult↗

Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls: clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia.

Subtle cytoarchitectural abnormalities of the rostral entorhinal cortex have been reported to be characteristic for schizophrenics. A main finding was the heterotopic displacement of clusters of lamina II neurons (which appeared morphologically immature) into layer III. Recent findings suggesting a considerable cytoarchitectural heterogeneity of the normal entorhinal cortex renewed interest in this problem and prompted the question of the extent to which 'aberrantly' located cell clusters are really disease-related. Being blind to the clinical diagnosis, we analyzed quantitatively the amount of entorhinal heterotopias in schizophrenics (n = 31), controls (n = 45) and depressive patients (n = 7). It was revealed that heterotopic cell clusters occurred in schizophrenics and controls with roughly the same frequency (amount of clusters per section). In depressive, there were significantly more heterotopias than in controls (right hemisphere). Our data show that heterotopias are common to the rostral part of the human entorhinal cortex and are not a suitable neuroanatomical marker of schizophrenia.

Adult↗

Compartmental volumetry of the superior temporal gyrus reveals sex differences in schizophrenia--a post-mortem study.

Brain imaging studies have shown superior temporal gyrus (STG) volume loss and abnormal patterns of asymmetry in schizophrenia; however, these are not consistent findings. Post-mortem volumetry of three different STG regions (defined by external landmarks) was used to compare 17 schizophrenics to 20 age- and sex-matched controls. Total STG volumes did not differ. A significant gray-matter volume reduction in schizophrenics was observed in the middle compartment (reaching from the mamillary body to the lateral geniculate body). This may have been related to reduced length of this region, particularly in schizophrenic females. These results reflect the problematic issue of defining boundaries of macroscopic brain structures.

Analysis of Variance↗

Schizophrenia and anteroventral thalamic nucleus: selective decrease of parvalbumin-immunoreactive thalamocortical projection neurons.

This study was designed to examine possible anatomical changes of thalamocortical circuits in schizophrenics. Previous immunocytochemical studies have shown that parvalbumin, a calcium-binding protein, occurs in thalamocortical projection neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus (AN). Using parvalbumin-immunocytochemistry we investigated the densities of thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and controls (n = 14). The densities of all neurons in the AN were estimated by Nissl-staining. The majority of thalamocortical projection neurons in AN were identified by parvalbumin-immunoreaction. Significantly reduced densities of thalamocortical projection neurons were estimated in the right (P = 0.003) and left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in right and left AN were also diminished in schizophrenics; however, these decreases did not reach statistical significance. The reductions of parvalbumin-positive thalamocortical projection neurons were not correlated with the length of disease, this finding supporting the neurodevelopmental etiology of structural abnormalities in schizophrenia.

Adult↗

[Qualitative evaluation of brain structure in CT in panic disorders].

This CT study was designed to assess brain morphology in panic disorder with and without agoraphobia. Twenty-one patients and 21 normal control subjects matched for age and sex were investigated. Frontal and parieto-occipital cortex, temporal cortex, lateral ventricles and 3rd ventricle were evaluated by qualitative assessment on a 3-point scale (normal, questionable, abnormal). Patients showed significant bilateral enlargement of cortical cerebrospinal fluid (CSF) spaces (p < 0.01). The rating "abnormal" was given to none (0%) of the normal controls, but to 7 (33.3%) of the patients. Explorative analysis showed that these abnormalities were predominantly located in prefrontal regions. No qualitative differences were seen in the temporal cortex, lateral ventricles or third ventricle. These findings support the hypothesis that alterations in brain morphology are involved in the etiology of panic disorder. The lack of a correlation between CSF enlargement and duration of illness suggests that frontal CSF enlargement is a neurobiological vulnerability marker in panic disorder.

Adult↗

Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics.

The neuroanatomical distribution of nitric oxide synthase-immunoreactive neurons was investigated in post mortem hypothalami of 10 patients suffering from schizophrenia, eight patients with depression and 13 matched control cases. Neuronal nitric oxide synthase containing nerve cells were detected in several hypothalamic nuclei including the medial preoptic region, the ventromedial, infundibular and suprachiasmatic nuclei and the lateral hypothalamus. The vast majority of hypothalamic nitric oxide synthase-immunoreactive neurons was found to be located in the paraventricular nucleus. Both magno and parvocellular paraventricular neurons contained the enzyme. A small subset of immunoreactive parvocellular paraventricular neurons co-expresses corticotropin-releasing hormone. The supraoptic nucleus did not contain nitric oxide synthase-immunoreactive neurons. Cell counts of paraventricular nitric oxide synthase-positive neurons in controls, schizophrenics and depressed patients revealed a statistically significant reduction of cell density in the right paraventricular nucleus of depressed patients and schizophrenics as compared to controls. The total amount of nitric oxide synthase-immunoreactive paraventricular neurons was smaller in depressive and schizophrenic patients than in normal cases. The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitric oxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.

Adult↗