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B Bogerts

Publications and source records attributed to B Bogerts.

At least 19 recordsLinked to original sources
PubMed2007

Quantification of total mitochondrial DNA and mitochondrial common deletion in the frontal cortex of patients with schizophrenia and bipolar disorder.

Data published during the last decade are suggestive of a role for mitochondrial dysfunction in the pathogenesis of schizophrenia, bipolar disorder and other psychiatric diseases. In order to determine if the mitochondrial deficits reported in the literature are caused by abnormalities in the mitochondrial DNA of psychiatric patients, we quantified mitochondrial DNA (mtDNA) levels and the 5 kb common mitochondrial deletion (CD) in postmortem frontal cortex tissue. The mitochondrial CD and mtDNA levels were measured in tissue obtained from the frontal cortex (Brodmann Area 46) of 144 individuals (45 patients with schizophrenia, 40 patients with bipolar disorder, 44 controls, and 15 patients with major depression). These variables were measured using newly developed SYBR green and TaqMan real time PCR assays. Both the TaqMan and the SYBR green assays gave similar results. There was no statistically significant difference for the quantity of the common mitochondrial deletion between controls and patients. We also did not detect a difference in the mtDNA levels amongst the diagnosis groups. There were statistically significant differences for the evaluated parameters for smokers, schizophrenic patients on antipsychotic drugs at time of death, and bipolar patients with antidepressant use and alcohol abuse. Based on this study and other reports, we conclude that neither the common mitochondrial deletion nor changes in mitochondrial DNA levels are likely to account for the mitochondrial changes associated with bipolar disorder or schizophrenia. The effect of premortem agonal factors and medication on mitochondrial dysfunction still needs further elucidation.

Adult↗
PubMed2007

[Cenesthesia as a rare differential diagnosis of persistent idiopathic facial pain].

Cenesthesia is portrayed as a rare differential diagnosis to persistent idiopathic facial pain, including the resulting therapy with antipsychotics. In this case report a female patient developed persistent facial pain 2 years after manifestation of a depressive disorder. The symptoms appeared as a bizarre pain phenomenon closely resembling the psychotic phenomenon of cenesthesia (body hallucinations). Treatment with imipramine and doxepin or a combination of venlafaxin, carbamazepine, and tilidine N had not been successful. Based on diagnostic classification of the complaint as cenesthesia in the context of a depressive disorder, add-on therapy of the atypical antipsychotic ziprasidone was administered. This led to clear improvements in mood and pain symptoms after 4 weeks of treatment.

Chronic Disease↗
PubMed2006

Early neonatal and postweaning social emotional deprivation interferes with the maturation of serotonergic and tyrosine hydroxylase-immunoreactive afferent fiber systems in the rodent nucleus accumbens, hippocampus and amygdala.

The impact of early emotional experience on the development of serotonergic and dopaminergic fiber innervation of the nucleus accumbens, hippocampal formation and the amygdala was quantitatively investigated in the precocious rodent Octodon degus. Two animal groups were compared: 1) degus which were repeatedly separated from their parents during the first three postnatal weeks, after weaning they were individually reared in chronic social isolation and 2) controls which were reared undisturbed with their families. In the deprived animals 5-hydroxytryptamine-immunoreactive fiber densities were increased in the core region of the nucleus accumbens (up to 126%), in the central nucleus of the amygdala (up to 112%) and in the outer subregion of the dentate gyrus stratum moleculare (up to 149%), whereas decreased fiber densities were detected in the dentate subgranular layer (down to 86%) and in the stratum lacunosum of the hippocampal cornu ammonis region 1 (down to 86%). Tyrosine hydroxylase-immunoreactive fiber densities were increased in the core (up to 115%) and shell region (up to 113%) of the nucleus accumbens of deprived animals, whereas decreased fiber densities (down to 84%) were observed in the hilus of the dentate gyrus. In the stratum granulosum and subgranular layer the fiber densities increased up to 168% and 127% respectively. In summary, these results indicate that the postnatal establishment of the monoaminergic innervation of limbic areas is modulated in response to early emotional experience, and that this environmental morphological adaptation is highly region specific.

Adaptation, Physiological↗
PubMed2006

[Neuroethics--a future discipline?].

Progress in neuroscience leads not only to novel therapeutic opportunities but also raises several ethical problems. These problems are often subsumed under the term "neuroethics," of which the definition and purpose often remain unclear. We discuss the problems of informed consent, free will, sense of self, and personality in light of recent neuroscientific progress. Due to distinct categories and frames of reference, these philosophical-ethical terms cannot be limited only to the brain; the development of systematic relations is suggested. This accounts for the "special ethical position of the brain." It is concluded that only this sense can neuroethics account for the ethical complexity in neuropsychiatric disorders.

Ethics, Medical↗
PubMed2006

[Differential diagnosis of anorexia nervosa and depression. A case report of Addison's disease in a female patient].

Similar symptoms make the differential diagnosis of anorexia nervosa and Addison's disease difficult at times: vomiting, weight loss, hypotension, depressed mood, reduced drive, and increased irritability can occur in both disorders. Psychological factors are then frequently presumed to be causative, so that the diagnosis of Addison's disease is made only years after the onset of the disease. Against this background, our case report presents important differential features, particularly with regard to consultative psychiatry.

Addison Disease↗
PubMed2006

[Subjective experience and neuronal integration in the brain: do we need a first-person neuroscience?].

Unlike other medical disciplines psychiatry can be characterized by the special importance of subjective experience. Since subjective experience is tied to First-Person-Perspective and investigation of the brain is possible only in Third-Person-Perspective, the question how subjective experience can be linked to neuronal processes is raised in psychiatry. We suggest a novel methodological approach, First-Person-Neuroscience where subjective experience can be linked directly and systematically to neuronal processes. Due to complexity of the structures and contents of subjective experience, localization in specific brain regions seems inappropriate. Instead, the interplay and coordination of neuronal activity across several brain regions, so-called neuronal integration, should be considered in First-Person-Neuroscience. This is illustrated by two principles of neuronal integration, top-down modulation and reciprocal modulation, whose abnormal function can be related to subjective experience of patients with catatonia and depression. It is concluded that First-Person-Neuroscience can contribute to reveal abnormal brain function in psychiatric disorders and ultimately to development of diagnostic and therapeutic markers.

Brain↗
PubMed2006

[Neurobiological basis of depressive disorders].

Depressive disorders belong to the most frequent diseases worldwide showing a lifetime prevalence of up to 20%. Moreover they are one of the leading causes for the amount of years lived with disability. Increasing knowledge about the pathological mechanisms underlying depressive syndromes is obtained by using modern neurobiological research-techniques. Thereby some older theories that have been the basis of emotion-research for decades--like the monoamine hypothesis--have been strengthened. In addition new aspects of the pathological processes underlying depressive disturbances have been unraveled. In this review established models and recent findings will be discussed, to bridge various research-fields, ranging from genetics, epigenetics and morphological changes to the functional consequences of depression. Finally therapeutic implications that could be derived from these results will be presented, showing up putative possibilities for diagnosis and treatment of depressive syndromes.

Brain↗
PubMed2006

Increased cerebrospinal fluid and serum levels of S100B in first-onset schizophrenia are not related to a degenerative release of glial fibrillar acidic protein, myelin basic protein and neurone-specific enolase from glia or neurones.

OBJECTIVE: To assess levels of glial fibrillar acidic protein (GFAP), myelin basic protein (MBP), neurone-specific enolase (NSE) and S100B in patients with first-onset schizophrenia. METHOD: We investigated CSF and serum samples from 12 patients with first-onset schizophrenia and from 17 control subjects by ELISA (GFAP, MBP) or immunoluminometric sandwich assays (NSE, S100B). RESULTS: Patients with schizophrenia had significantly higher levels of S100B in CSF (p = 0.004; 2.73 (SD 0.80) v 1.92 (0.58) microg/l) and serum (p = 0.032; 0.09 (0.03) v 0.08 (0.02) microg/l) in comparison with those in the matched control group. No diagnosis-dependent differences of protein concentration were seen for GFAP, MBP and NSE. DISCUSSION: Our finding of increased levels of S100B in patients with schizophrenia without an indication for significant glial (GFAP, MBP) or neuronal (NSE) damage may be interpreted as indirect evidence for increased active secretion of S100B during acute psychosis.

Adolescent↗
PubMed2005

Hypothalamic nitric oxide synthase in affective disorder: focus on the suprachiasmatic nucleus.

Depression is frequently associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to repeated episodes of hypercortisolemia. Hypothalamic paraventricular neurons are believed to trigger these processes by aberrant generation and/or release of corticotropin releasing hormone, oxytocin, vasopressin, and nitric oxide (NO). Recent findings from two independent laboratories have demonstrated that the suprachiasmatic nucleus, which in part controls the cellular activity of paraventricular neurons (PVN), is also involved in affective disorder. The aim of the present study was to elucidate by stereological analysis, whether suprachiasmatic nucleus (SCN) nitric oxide synthase and neurophysin generating neurons are affected in neuropsychiatric disorders. We show that compared to controls the number of nitric oxide synthase immunoreactive neurons is greatly reduced both in depression and in schizophrenia. In subjects with affective disorder there was a correlation between the number of NOS-expressing cells and duration of treatment with antidepressants. The number of neurophysin-expressing SCN neurons was also fewer in cases with mood disorder. It is concluded that SCN-derived NO may be a relevant pathophysiological factor in neuropsychiatric disorders.

Adult↗
PubMed2005

The Alzheimer disease-related calcium-binding protein Calmyrin is present in human forebrain with an altered distribution in Alzheimer's as compared to normal ageing brains.

The EF-hand calcium binding protein Calmyrin (also called CIB-1) was shown to interact with presenilin-2 (PS-2), suggesting that this interaction might play a role in the pathogenesis of Alzheimer's disease (AD). Here we have investigated the distribution of Calmyrin in normal human and AD brain. In normal brain Calmyrin immunoreactivity was unevenly distributed with immunostaining in pyramidal neurones and interneurones of the palaeo-cortex and neocortex, cerebellar granule cells and hypothalamic neurones of the paraventricular, ventromedial and arcuate nuclei. Moderate immunoreactivity was present in hippocampal pyramidal cells and stronger in dentate gyrus neurones. Thalamic and septal neurones were devoid of immunoreactivity. No apparent differences were visible between stainings of brain sections from younger and older nondemented patients. In AD brain a substantial loss of Calmyrin-immunopositive neurones was observed in all regions, especially in cortical areas. Still immunoreactive neurones, however, displayed stronger staining that was especially concentrated in perinuclear regions. Calmyrin immunosignals were in part associated with diffuse and senile plaques. Thus, although protein levels of Calmyrin are low in human forebrain, its cellular localization as well as its altered distribution in AD brain suggest that it may be involved in the pathogenesis of AD.

Adult↗
PubMed2003

Regio entorhinalis in schizophrenia: more evidence for migrational disturbances and suggestions for a new biological hypothesis.

Recently we were able to replicate the original finding of migrational disturbances in the entorhinal cortex (ERC) of schizophrenic patients by measuring the distance of pre-alpha cell clusters to the pial surface. In order to replicate this finding, we performed a detailed analysis of the pre-alpha cell clusters in the ERC in post mortem brains of 22 schizophrenic patients and 15 control subjects. Cluster position relative to gray/white matter boundary were measured and normalized by the widths of the gray matter. In the ERC the pre-alpha cell clusters were situated significantly closer to the gray/white matter junction compared to normal controls (around 30 %, F = 9.52, p = 0.004). No specific effects of sex, age or region of investigation were found. In summary, this is another quantitative replication of pre-alpha cell cluster migrational disturbances in schizophrenia, which are possibly linked to neurobiological abnormalities, e.g. myeloarchitectonic changes. This supports the notion that developmental abnormalities are a core feature of schizophrenia and that the search for candidate genes has to include this aspect, too. However, it is very probable that vulnerability-associated changes - as outlined here - have to be distinguished from disease-related changes.

Age Factors↗
PubMed2003

Therapeutic drug monitoring of clozapine and relapse--a retrospective study of routine clinical data.

OBJECTIVE: Therapeutic drug monitoring (TDM) of the atypical antipsychotic drug clozapine is recommended. Clinical studies have indicated a therapeutic window for clozapine serum levels in schizophrenic and schizo-affective patients during acute treatment, i.e. for patients who do not respond to treatment with typical antipsychotics. However, despite the frequent use of clozapine also in maintenance treatment, very few data are available showing the relationship between serum levels of clozapine and the prevention of relapse. Thus, the primary objective of the study was to investigate the relationship between serum levels ofclozapine and relapse during maintenance treatment. METHODS: A retrospective study of routine TDM-data was conducted. Samples obtained on an acute treatment ward from patients with < 4 days hospitalization (recent admissions) were regarded as samples associated with relapse. Samples which can be attributed to an intoxication were identified as described in the TDM-form. The serum level of clozapine, as well as age, gender, smoking habits, concurrent drugs, psychiatric diagnosis and dose of clozapine were evaluated. Data analysis was performed on individual samples and, alternatively, on multiple samples from a single patient which are summarized according to a typical clinical situation. RESULTS: 404 serum levels were measured in 86 patients. After exclusion of patients receiving acute treatment, 65 relevant clinical situations were identified in 50 patients: 12 relapses, 8 intoxications (a total of 20 situations with poor outcome) and 45 situations involving patients with good maintenance outcome. Samples involving relapse had serum levels of 198 +/- 211 ng/ml (10-624), intoxications had serum levels of 1,969 +/- 705 ng/ml (900-2,900) and those with good outcome had serum levels of 384 +/- 255 ng/ml (56-1,028) (mean +/- SD (range)). By means of sensitivity of receiver operating characteristic curves (ROC) a lower limit of the therapeutic window can be estimated at about 50-250 ng/ml and an upper limit at about 745-1,050 ng/ml. The frequencies of good and poor outcome were significantly different within and outside these ranges, e.g. chi2 = 11.8 and p < 0.001 for 250 to 745 ng/ml. Comparison of only good outcome and relapse provided a significant difference in the serum level of clozapine (Student's t-test p = 0.024). However, 67% of relapses were predicted in a model of logistic regression only if the variables serum level and concurrent treatment with other psychotropic drugs were included simultaneously as independent variables. Neither variable was able to predict relapse if used as a single variable in separate models. Finally, it was found that serum levels of clozapine were increased in women, in aged patients and in nonsmokers. CONCLUSIONS: It is tentatively concluded that serum levels of clozapine < 50 ng/ml are related to relapse irrespective of concurrent psychotropic drugs. In cases where there are no concurrent psychotropic drugs, serum levels of clozapine < 250 ng/ml are associated with relapse. The risk of relapse is low for serum levels of clozapine > 250 ng/ml irrespective of concurrent psychotropic drugs. The risk of intoxication is increased with serum levels > 750 ng/ml. The TDM of clozapine is recommended during maintenance treatment.

Adult↗
PubMed2002

Circumscribed numerical deficit of dorsal raphe neurons in mood disorders.

BACKGROUND: Neurocircuits comprising limbic, striato-pallidal and thalamo cortical brain areas are assumed to be involved in the pathophysiology of mood disorders. All these brain regions receive serotonergic afferents arising from the rostral raphe, mainly the dorsal raphe. Although serotonergic systems appear to be involved in the pathology of mood disorders, there is uncertainty as to whether structural alterations in raphe nuclei exist alongside a functional dysregulation of the serotonergic system. METHODS: In the brains of 12 patients with mood disorders (major depressive disorder N= 6, bipolar disorder N = 6) and 12 normal subjects we performed a morphometric post-mortem study on neuronal morphology in all subnuclei of the dorsal raphe nucleus using Nissl stained 20 microm axial serial sections of the brainstem. RESULTS: The number of neurones of the ventrolateral subnucleus of the dorsal raphe was reduced by 31 % in patients with mood disorders compared with non-psychiatric control subjects. Ventrally located subnuclei of the rostral dorsal raphe (ventrolateral, ventral, interfascicular) taken together also showed a smaller number of neurones. Neurone numbers of the dorsal and the caudal subnucleus and volumes of all single subnuclei appeared to be unchanged. Analysis of morphological neuronal types revealed a smaller number of triangular neurones in the ventrolateral subnucleus. Numbers of ovoid and round neurones in the ventrolateral subnucleus also showed a trend to reduction. No correlation was found between neurone numbers in any subnucleus of the dorsal raphe and duration of illness. Neurone numbers did not differ in any subnucleus between patients with unipolar and those with bipolar affective disorder. CONCLUSIONS: Results indicate that patients with primary mood disorders have a circumscribed numerical neuronal deficiency in the dorsal raphe. This structural deviation may contribute to impaired serotonergic innervation of brain regions which are involved in the pathology of mood disorders.

Adult↗
PubMed2002

Fewer beta-endorphin expressing arcuate nucleus neurons and reduced beta-endorphinergic innervation of paraventricular neurons in schizophrenics and patients with depression.

In order to elucidate whether the hypothalamic expression of beta-endorphin is altered in patients with mental disorders we studied the cellular localization of the peptide in arcuate nucleus neurons as well as the beta-endorphinergic innervation of paraventricular neurons in nine schizophrenics, six subjects with depression, and nine controls. A polyclonal antiserum against beta-endorphin was employed for the immunohistochemical detection of the peptide in sections of postmortem human brains. Quantitative analysis revealed that the number of beta-endorphin-containing arcuate neurons was statistically reduced in schizophrenics and depressives in comparison to controls. Moreover, the number of endorphinoceptive (i.e. beta-endorphin-innervated) paraventricular nerve cells was also lower in psychiatric patients than in control cases. Our results showing an altered endorphinergic system in human hypothalami of schizophrenics and depressives might contribute to a renewal of interest in this peptide as a possible factor of importance in psychiatric disorders.

Adult↗
PubMed2001

[Experience guided neuronal plasticity. Significance for pathogenesis and therapy of psychiatric diseases].

Whereas the basic wiring of the mammalian central nervous system is genetically predefined, its fine tuning throughout different phases of infancy, childhood, and adulthood are highly experience-dependent. There is growing evidence from a variety of experimental data that juvenile experience and learning events modulate the functional maturation of the brain, thereby shaping the neuronal substrate for the development of intellectual and socioemotional capacities. Since early experiences occur during phases of elevated neuronal and synaptic plasticity, they induce an "imprinting" of synaptic connectivity and neural circuitry in the infant brain. Results from experimental research support the hypothesis that impoverished intellectual stimulation and traumatic socioemotional experience during early childhood may impair the formation of functional brain pathways, in particular of the limbic circuits, which play a major role in emotional behavior and learning. Such defective systems, representing functional "scars" in the brain, may be the neuronal basis of a variety of mental disorders and clinical symptoms caused by early stressful psychosocial environments. A basic thesis of this paper is that mechanisms involved in neuronal learning and memory are not only used and reused in structuring the CNS during the initial establishment of connections in the immature brain but also can be employed in molding personality and behavior during psychotherapy in adulthood.

Adult↗
PubMed2001

Increased number of nitric oxide synthase immunoreactive Purkinje cells and dentate nucleus neurons in schizophrenia.

There is growing interest in the cerebellum as a site of neuropathological changes in schizophrenia. Reports showing that schizophrenics have higher nitric oxide synthase (NOS) activity and MAPKinase levels in the vermis, point to possible aberrations in the cerebellar signal transduction of schizophrenics. It has been speculated that Ca(2+)-dependent extracellular to intracellular signal transduction may be disrupted in the cerebellum of schizophrenics. We decided to test this hypothesis by studying the nitrergic system and markers of the Ca(2+)-triggered signal cascade in the cerebellum of schizophrenics, depressives and controls. The cellular distribution of two calcium sensor proteins (VILIP-1 and VILIP-3) and of neuronal NOS immunoreactivity was studied morphometrically in the flocculonodulus, the inferior vermis and the dentate nucleus of 9 schizophrenics, 7 depressive patients and 9 matched controls. In comparison to controls and depressed patients there were fewer Nissl-stained neurons in the dentate nucleus of schizophrenics. The number of NOS-expressing Purkinje neurons was however strongly increased. In the flocculonodulus and the vermis no differences between the groups were found with regard to the density of Nissl-stained Purkinje cells. The number of NOS-expressing Purkinje neurons was increased in schizophrenics, however. No differences between schizophrenics, depressives and controls were found in the number of VILIP-1 immunoreactive dentate nucleus neurons and VILIP-3 immunoreactive vermal and flocculonodular Purkinje cells. Our data provide further histochemical evidence in favor of structural abnormalities in discrete cerebellar regions of schizophrenics. They confirm and extend earlier reports of increased cerebellar NOS immunoreactivity in schizophrenia and point to possible neurodevelopmental disturbances. Our failure to show an altered expression of two calcium sensor proteins possibly points to a less important role of calcium signaling in cerebellar pathology of the disease.

Adult↗
PubMed2001

Lack of neuronal NOS has consequences for the expression of POMC and POMC-derived peptides in the mouse pituitary.

The relevance of NO in neuroendocrine signalling has been investigated by analysis of cellular expression of pro-opiomelanocortin (POMC) and the POMC-derived peptides beta-endorphin, alpha-melanocyte stimulating hormone and adrenocorticotropin. Expression patterns were studied in the pituitary gland of 150-day old wild-type and neuronal-NOS (nNOS) knock-out mice by using immunohistochemistry, in situ hybridization and Northern blot analysis. Remaining NO-generating capacities in the knock-out mice were demonstrated by immunohistochemical localization of inducible, endothelial and neuronal NOS isoforms. Quantitative analysis revealed that cellular expression of POMC mRNA was drastically reduced in the pituitary of knock-out mice in comparison to controls. In situ hybridization studies demonstrated that this reduction was most pronounced in the intermediate lobe, while the anterior lobe was much less affected. Immunostaining for the proteolytic fragments of POMC was significantly reduced in the intermediate lobe cells of knock-out mice. A moderate reduction of immunostaining for these peptides was also observed in adenopituitary cells of nNOS knock-out mice. Our data demonstrate that the lack of nNOS substantially affects cellular levels of pituitary opioid peptides, which may have consequences for the response of these animals to stress and pain.

Adrenocorticotropic Hormone↗