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Biomedical subjects

P Falkai

Publications and source records attributed to P Falkai.

At least 37 records · Page 2Linked to original sources

[Psychological distress associated with acute tinnitus].

BACKGROUND: We question whether patients with acute tinnitus can be differentiated in their perceived handicap and emotional distress. Dysfunctional mechanisms for coping with stress and illness in patients with acute tinnitus were investigated. METHODS: Twenty patients (symptoms for less than 1 week) were examined for distress due to tinnitus (TF), degree of depression (BDI), global distress (SCL- 90-R) and coping with stress (SVF). RESULTS: Patients could be differentiated in terms of their psychological distress and annoyance caused by the symptoms. There is a high correlation between the degree of depression, dysfunctional way of coping with stress and emotional distress caused by tinnitus. Dysfunctional stress coping strategies are found more frequently in highly affected patients. CONCLUSION: Patients with acute tinnitus can be differentiated in terms of their distress and the psychological impairment caused by their symptoms. These results suggest that the immediate reaction to the manifestation of tinnitus might be of prognostic value for the level of emotional distress experienced in chronic tinnitus. The question arises of whether psychological intervention in the acute stage of tinnitus might be beneficial.

Acute Disease↗

[Changes in brain structure in bipolar affective disorders].

The neurobiological basis of bipolar affective disorders is unknown. However, neuroanatomic circuits of mood regulation have been hypothesized. Neuroimaging revealed volumetric changes of specific brain structures in these circuits. The most prominent abnormality is enlargement of the amygdala. In addition there might be structural changes in the frontal lobe, cerebellum, and pituitary. The findings in bipolar disorder differ from those in unipolar depression and schizophrenia. For further identification of the neurobiological basis of bipolar disorders, structural neuroimaging combined with functional neuroimaging such as magnetic resonance spectroscopy, neuroendocrinological studies, and genetical analyses are required to subgroup patients with bipolar disorder by diagnostic, prognostic, and therapeutic criteria.

Affect↗

[Changes in brain structure caused by neuroleptic medication].

A couple of studies showed that neuroleptic treatment affects brain morphology. This paper reviews findings of volumetric longitudinal studies on treated schizophrenics, longitudinal studies considering the effect of different neuroleptic treatments on brain morphology, and studies on neuroleptic-naive patients with schizophrenia. The latter studies show enlargement of ventricles, diminished volume of the thalamus and reduced gray matter in different cortical regions. Findings on the nucleus caudatus, hippocampus, and amygdala are inconsistent. The volumes of the putamen and globus pallidus are unchanged. Medication with typical antipsychotics leads to increased volume of the nucleus caudatus while atypical antipsychotics do not change the volume of the nucleus caudatus.

Antipsychotic Agents↗

Imaging of central nAChReceptors with 2-[18F]F-A85380: optimized synthesis and in vitro evaluation in Alzheimer's disease.

In vivo labeling of the nicotinic acetylcholine receptors (nAChR) could be a useful tool for early diagnosis of neurodegenerative disorders. 2-[18F]F-A85380 (2-[18F]Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine), a ligand with high affinity to the beta2 subunit of the nAChRs, has been shown to label neurons in the nAChR-rich thalamus, cortex and striatum in baboons. We report an optimized synthesis resulting in an uncorrected yield of 58% in 45 min (precursor 2), enabling efficient production intended for clinical use. Incubation of normal rat brain sections with 2-[18F]F-A85380 with subsequent autoradiographic analyses showed the expected distribution in nAChR areas. In human brain sections of Alzheimer's disease (AD) a decrease of 2-[18F]F-A85380 uptake to 36% of the control group was measured in the thalamus and also in the occipital cortex. These findings suggest that 2-[18F]F-A85380 is a promising PET-ligand in the diagnosis of AD.

Alzheimer Disease↗

Erythropoietin: a candidate compound for neuroprotection in schizophrenia.

Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.

Adult↗

[Schizophrenia].

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Brain Chemistry↗

[Schizophrenia].

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Diagnosis, Differential↗

Etiopathogenetic mechanisms in long-term course of schizophrenia.

Schizophrenia is a severe mental disorder with a relapsing long-term course in 80 % of the sufferers. The underlying neurobiological principles of the long-term course are widely unknown. Therefore an attempt is made to evaluate data from structural imaging and neuropsychology to shed some light on these mechanisms. Interestingly there was a significant correlation between length of illness and volume reduction in the prefrontal grey matter in schizophrenia. There was a lack of such a correlation for the whole brain volume, white matter volume or the grey matter volume outside the prefrontal lobe. Furthermore none of the neuropsychological measures correlated with length of illness. Both findings are supported by data from prospective studies up to five years demonstrating a significant loss of frontal grey matter volume, but no change of cognitive dysfunction in the course of time. The attempt is made to connect prefrontal grey matter loss with post-mortem findings of reduced neuropil but preserved cytoarchitecture leading to recently described candidate genes and their function.

Brain↗

Neural correlates of first-person perspective as one constituent of human self-consciousness.

Taking the first-person perspective (1PP) centered upon one's own body as opposed to the third-person perspective (3PP), which enables us to take the viewpoint of someone else, is constitutive for human self-consciousness. At the underlying representational or cognitive level, these operations are processed in an egocentric reference frame, where locations are represented centered around another person's (3PP) or one's own perspective (1PP). To study 3PP and 1PP, both operating in egocentric frames, a virtual scene with an avatar and red balls in a room was presented from different camera viewpoints to normal volunteers (n = 11) in a functional magnetic resonance imaging experiment. The task for the subjects was to count the objects as seen either from the avatar's perspective (3PP) or one's own perspective (1PP). The scene was presented either from a ground view (GV ) or an aerial view (AV ) to investigate the effect of view on perspective taking. The factors perspective (3PP vs. 1PP) and view (GV vs. AV ) were arranged in a two-factorial way. Reaction times were increased and percent correctness scores were decreased in 3PP as opposed to 1PP. To detect the neural mechanisms associated with perspective taking, functional magnetic resonance imaging was employed. Data were analyzed using SPM'99 in each subject and non-parametric statistics on the group level. Activations common to 3PP and 1PP (relative to baseline) were observed in a network of occipital, parietal, and prefrontal areas. Deactivations common to 3PP and 1PP (relative to baseline) were observed predominantly in mesial (i.e., parasagittal) cortical and lateral superior temporal areas bilaterally. Differential increases of neural activity were found in mesial superior parietal and right premotor cortex during 3PP (relative to 1PP), whereas differential increases during 1PP (relative to 3PP) were found in mesial prefrontal cortex, posterior cingulate cortex, and superior temporal cortex bilaterally. The data suggest that in addition to joint neural mechanisms, for example, due to visuospatial processing and decision making, 3PP and 1PP rely on differential neural processes. Mesial cortical areas are involved in decisional processes when the spatial task is solved from one's own viewpoint, whereas egocentric operations from another person's perspective differentially draw upon cortical areas known to be involved in spatial cognition.

Adult↗

[White matter alterations in neurodegenerative and vascular dementia].

Due to a significant overlap of the two syndromes, differentiation of degenerative dementia of the Alzheimer-type from vascular dementia may be difficult even when imaging studies are available. White matter changes occur in many patients suffering from Alzheimer's disease. Little is known about the impact of white matter changes on the course and clinical presentation of Alzheimer's disease. High sensitivity of MRI in the detection of white matter alterations may account for over-diagnosing vascular dementia. The clinical significance of white matter alterations in dementia is still a matter of debate. The article reviews current concepts about the role of white matter alterations in dementia.

Age Factors↗

Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins.

Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n=30) compared with healthy subjects (n=27), overall white matter showed 12% lower myelin water fraction (P=0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P=0.002). The left anterior genu was affected in both first-episode (P=0.035) and chronic patients (P=0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2',3'-cyclic nucleotide 3'-phosphodiesterase by 33%, P=0.05; myelin-associated glycoprotein by 27%, P=0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

[Homocysteine and dementia].

Homocysteine is a vascular risk factor including cerebral macroangiopathy and microangiopathy. Furthermore, there might also be an association with cognitive disorders including vascular dementia and Alzheimer's disease. Hyperhomocysteinemia linked with cognitive impairment might be an indirect marker for low concentrations of vitamin B 12, vitamin B 6 or folate, resulting from low intake or from an impaired transport of the vitamins to the brain. Another possibility is a direct harmful effect of homocysteine to cognition via vascular and neurotoxic pathophysiologic mechanisms. Because hyperhomocysteinemia is a potentially reversible risk factor and can be identified early, it should be investigated by prospective intervention studies whether lowering homocysteine levels by vitamin supplementation could reduce incidence and progression of cognitive disorders.

Alzheimer Disease↗

[The importance of interneurons in schizophrenic and affective disorders].

In brains of patients with schizophrenic and affective disorders pathomorphological changes have been shown focussing in frontal and temporal cortex. The volume reduction in prefrontal cortex of schizophrenic patients is hypothesized to be based on a reduction of neuropil. A decrease of synaptic proteins and a decrease of dendritic spines of pyramidal cells can additionally be the origin of disconnections of neurons. Affection of the glutamatergic, GABA-ergic and dopaminergic system and reduction of interneurons could be the correlate of a deficient neuronal network which might be combined with exogen factors generate psychotic symptoms. Reelin and associated proteins are candidate molecules. Their dysregulation might explain essential features of the dysfunctional network of schizophrenia.

Brain↗

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↗

Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness.

Recent imaging and postmortem studies suggest that impaired connectivity is involved in the pathophysiology of schizophrenia and major affective disorders. We investigated the presynaptic proteins complexin (Cx) I and Cx II in postmortem prefrontal cortex in schizophrenia (n = 13; six suicide, seven nonsuicide), major depression (n= 11, all suicide) and controls (n = 11) with an enzyme-linked immunoadsorbent assay (ELISA). Overall analysis indicated a significant difference between groups (F = 3.93, P = 0.007). Cx I (enriched in inhibitory terminals) was decreased 33% in schizophrenia (26% in schizophrenia/nonsuicide, 42% in schizophrenia/suicide) and 27% in major depression. Cx II (enriched in excitatory terminals) was not significantly different. Analysis of the ratio of Cx II/Cx I was carried out as an indication of the balance of excitatory to inhibitory terminals. A significant difference between groups (ANOVA, F = 6.42, P = 0.005) was observed. The mean value of Cx II/Cx I was significantly increased by 34% in schizophrenia (26% in schizophrenia/nonsuicide and 43% in schizophrenia/suicide) and by 32% in depression compared with control (Student-Newman-Keuls test, P = 0.05). Immunoreactivities of the two complexins were highly correlated in all groups. However, compared with controls and depression, samples from cases with schizophrenia appeared to have relatively less Cx I for similar amounts of Cx II. Immunocytochemical studies of rat frontal cortex after 3 weeks treatment with chlorpromazine, trifluoperazine or haloperidol revealed no differences in complexins, synaptophysin, SNAP-25, syntaxin or VAMP in comparison with animals treated with vehicle. Alterations of complexins may contribute to the molecular substrate for abnormalities of neural connectivity in severe mental disorders.

Adaptor Proteins, Vesicular Transport↗