Biomedical subjects

P Falkai

Publications and source records attributed to P Falkai.

At least 73 records · Page 4Linked to original sources

PubMed1999

Essential functions of the human self model are implemented in the prefrontal cortex.

The human self model comprises essential features such as the experiences of ownership, of body-centered spatial perspectivity, and of a long-term unity of beliefs and attitudes. In the pathophysiology of schizophrenia, it is suggested that clinical subsyndromes like cognitive disorganization and derealization syndromes reflect disorders of this self model. These features are neurobiologically instantiated as an episodically active complex neural activation pattern and can be mapped to the brain, given adequate operationalizations of self model features. In its unique capability of integrating external and internal data, the prefrontal cortex (PFC) appears to be an essential component of the neuronal implementation of the self model. With close connections to other unimodal association cortices and to the limbic system, the PFC provides an internally represented world model and internal milieu data of the organism, both serving world orientation. In the pathophysiology of schizophrenia, it is the dysfunction of the PFC that is suggested to be the neural correlate for the different clinical schizophrenic subsyndromes. The pathophysiological study of psychiatric disorders may contribute to the theoretical debate on the neuronal basis of the self model.

Body Image↗

PubMed1999

[Genetics of schizophrenic disorders. New concepts and findings].

Schizophrenia is a genetic complex disease as it does not follow monogenic transmission while non-familial environmental factors have a strong additional impact. A heterogeneous, continuous phenotype is transmitted in families which can now be more precisely characterized. Genes coding for proteins with presumed pathophysiological relevance are apparently not playing a major causal role. However, in the last three years several (currently seven) candidate regions have been identified in a replicable manner by linkage studies. These regions are likely to host susceptibility genes for schizophrenia, but none of them has been identified up to now. Given these findings, polygenic transmission has now become very likely. The candidate regions are currently being narrowed down by various promising techniques.

Biomarkers↗

PubMed1999

Stability of RNA transcripts in post-mortem psychiatric brains.

RNA isolated from frozen human post-mortem brain tissue was used for analysis of five gene products with a recently developed sensitive and competitive RT-PCR technique. Samples varying in post-mortem intervals up to four days from controls, schizophrenics and alcoholics were analyzed. Evaluation of three housekeeping genes, as well as Trk B and Trk C demonstrated that the levels of mRNA transcripts were stable in brain samples at all time periods (one to four days) examined. This observation demonstrates that this RT-PCR protocol is a sensitive and reliable method to study relative amounts of mRNAs. The overall stability of housekeeping transcripts implicates the value of post-mortem brain samples for differential gene expression studies.

Actins↗

PubMed1999

Differential memory span--abnormal lateralization pattern in schizophrenic patients and their siblings?

The recurring digit span test is hypothesized to assess consolidation memory and hypothetically addresses neuropsychological left-temporohippocampal functioning, an area of the brain which is presumed to play a crucial role in schizophrenia. The present study applied the recurring digit span memory test and the recurring block span memory test (assumed to be an indicator of right-temporohippocampal functioning) to 106 acute schizophrenic patients (DSM-III-R), 49 siblings of these patients without DSM-III-R lifetime diagnoses as well as 53 non-related control subjects without DSM-III-R lifetime diagnoses. Results of our investigation indicate that schizophrenic patients differ from control subjects regarding recurring digit span in a reduced number of correct reproductions of recurring trials. Since performance of schizophrenic patients was only non-significantly different from control subjects regarding recurring block span memory, our findings point to a task-specific memory impairment in schizophrenia and argue against a generalized deficit in this disease. Furthermore, individuals at risk for schizophrenia also differed from control subjects concerning the recurring digit span memory test but not with regard to the recurring block span test. Therefore we conclude that the reduced cumulative learning curve of verbal material (reduced number of correct reproduction of recurring digit trials) in schizophrenic patients and their healthy siblings might represent a marker for the liability to schizophrenia and parallels neuroimaging findings concerning left-sided temporohippocampal abnormalities in this disease, which presumably play a key role in the etiology of schizophrenia.

Adult↗

PubMed1999

Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness.

Abnormalities of proteins involved in neurotransmission and neural plasticity at synapses are reported in schizophrenia, and may be markers of dysregulated neural connectivity in this illness. Studies of brain development and neural regeneration indicate a dynamic interplay between neural and oligodendroglial mechanisms in regulating synaptic plasticity and axonal sprouting. In the present study, markers of synapses (synaptophysin), plasticity (growth-associated protein-43) and oligodendrocytes (myelin basic protein) were investigated in anterior frontal cortex homogenates from individuals with schizophrenia and depression. Synaptophysin immunoreactivity was reduced in schizophrenics who died of natural causes relative to controls. Myelin basic protein immunoreactivity was decreased in both schizophrenics and depressed individuals who died by suicide. Overall, no changes were observed in growth-associated protein-43 immunoreactivity. However, a slight increase in immunoreactivity in depressed suicides relative to control was observed. These findings support the hypothesis that synaptic abnormalities are a substrate for disordered connectivity in severe mental illness, and suggest that synaptic-oligodendroglial interactions may contribute to the mechanism of dysregulation in certain cases.

Adult↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

Mirtazapine: other indications.

During the last decade, it became evident that antidepressants may represent a useful treatment option for a variety of primary psychiatric disorders other than depression. Improved understanding of both underlying etiology of these disorders and pharmacologic modes of action of available treatments has led to an improvement in conditions such as panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and premenstrual dysphoric disorder. In addition, evidence is accumulating that some new antidepressants may be of therapeutic value in treatment of some subtypes of depressive disorder previously unresponsive to treatment or difficult to treat, such as seasonal affective disorder, depression with atypical features, and recurrent brief depression. Mirtazapine is an antidepressant with mode of action different from other currently available antidepressants. A review of currently available data of mirtazapine's use in indications other than depression and in some types of depressive disorder is presented.

Adult↗

PubMed1999

The epidemiology of comorbidity between depression, anxiety disorders and somatic diseases.

Depression, generalized anxiety disorder and somatoform disorder are the most common psychiatric disorders in primary care and in the general population. These disorders also show an excess comorbidity which is substantially more common than expected on the basis of their prevalence rates both in primary care as well as in general population. There is no unique mechanism accounting for each of these excess comorbidity constellations. Multiple consequences underline the clinical relevance of comorbidity between these disorders: more psychosocial disability, substantially elevated risk for completed suicides and suicide attempts, worse clinical outcome and treatment response. Recognition of comorbidity is essential for improvement of treatment.

Anxiety Disorders↗

PubMed1998

Reduced tyrosine kinase receptor C mRNA levels in the frontal cortex of patients with schizophrenia.

Using a quantitative RNA-PCR approach tyrosine kinase receptor (trk) C mRNA levels were determined in brain material from the frontal cortex (BA10), temporal cortex (BA20) and cerebellum of control specimen and patients with schizophrenia, bipolar disorder or non-psychotic depression (15 subjects each). In the frontal cortex of schizophrenics there was a 5.8-fold reduction of trk C mRNA levels, which reached statistical significance (P < 0.05). Trk C levels in the cerebellum were positively correlated with lifetime fluphenazine equivalents (r = 0.54), suggesting that neuroleptics influence TRK C gene activity in the cerebellum. Moreover, the distinct medication-independent reduction of trk C mRNA may point to a disturbed neurotrophic gene activity in the frontal cortex of schizophrenic patients.

Adult↗

PubMed1998

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↗

PubMed1998

Projecting the sulcal pattern of human brains onto a 2D plane--a new approach using potential theory and MRI.

A new method is introduced to project the sulcal pattern of the brain surface onto a 2D plane. Twin brains are compared against each other using the planar representation. We obtained T1-weighted Flash-3D MRI volumes from 14 male twins (seven monozygotic, seven dizygotic) with 3 mm-thick coronal slices. The projection is based on potential theory: A virtual electrostatic field is calculated between the area of the segmented brain and a surrounding spherical electrode. Field lines starting from each border point of the segmented brain follow the gradient towards the sphere, leading to field line concentrations due to the underlying sulci. The unwrapped sphere surface with the number of field lines per area unit is used as the 2D representation of the sulcal pattern. The resulting brain projections show a distinctive pattern, and a visual assignment of the twin pairs from the unsorted set is possible because of a high similarity of the patterns between twin pairs. Global correlation coefficients for each pair of maps yield significantly higher values for matching monozygotic twin pairs (mean = 20.2, range 12.3-25.6) than for unmatched pairs (mean = 13.0, range 1.1-28.5). As a conclusion, our method allows us to map the location and depth of the sulci on a 2D plane. The resulting maps allow quantitative inter-individual comparisons on the entire brain or parts of the brain surface.

Adult↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Analysis of a polymorphism in the tuberous sclerosis (TSC2) gene does not predispose to schizophrenia.

The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of malformations in various organs including the brain. A polymorphism in the TSC2 gene has been found to be increased in gangliogliomas, a lesion which is associated with disturbed neuro-glial cell migration pattern. Since these pathomorphological changes are compatible with disturbed neuronal migration in schizophrenic brains, we investigated this polymorphism in 130 families with a schizophrenic index patient. A 222-bp fragment of genomic DNA containing the TSC2 variant was analyzed by SSCP. The analysis revealed that there is no association with schizophrenia.

Adult↗

PubMed1998

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↗

PubMed1998

Obstetric complications, treatment response and brain morphology in adult-onset and early-onset males with schizophrenia.

BACKGROUND: Substantial variability in age at onset of illness and course of illness exists between patients with schizophrenia. Recent studies suggest that age at illness onset may be useful in defining biologically and clinically distinct subgroups of patients. METHODS: Two hundred and ten males with schizophrenia were classified as early-onset or adult-onset according to their age at first hospitalization. Birth history, clinical functioning and treatment response was assessed in a subgroup of patients. Brain anatomy was assessed from CT scans in all patients and in 32 non-psychiatric control subjects. RESULTS: Patients with an early-onset were likely to have a history of obstetric complications, a poor response to neuroleptic treatment, and showed no relationship between ventricle size and duration of illness. Adult-onset patients were less likely to have obstetric complications, more likely to respond to treatment in the first years of illness, and showed an association between brain structure and duration of illness. CONCLUSIONS: The distinction between early- and adult-onset patients may have important aetiological and treatment implications.

Adolescent↗

PubMed1997

Gene expression and neuronal activity in schizophrenia: a study of polyadenylated mRNA in the hippocampal formation and cerebral cortex.

The abundance of polyadenylated messenger RNA (poly(A)+mRNA) reflects overall gene expression and provides an index on neuronal activity. Poly(A)+mRNA was measured in the hippocampal formation and in occipital, temporal, cingulate and frontal cortices (Brodmann areas 17, 22, 24 and 46, respectively) of 11 schizophrenic and 17 control subjects post mortem by in situ hybridization histochemistry with a 35S-oligodeoxythymidine probe. There were no differences in poly(A)+mRNA between cases and controls, except for a modest decrease in the parahippocampal gyrus of the schizophrenics which may be attributable to cytoarchitectural differences in this area in the disease. The unchanged level of poly(A)+mRNA in all other regions argues against the existence of a widespread or sustained alteration in the metabolic activity of cortical neurons in schizophrenia. It also provides a further indication that the differential expression of individual transcripts reported in the disease is not merely reflecting changes in overall gene expression.

Adult↗