Biomedical subjects

Zoltán Janka

Publications and source records attributed to Zoltán Janka.

At least 19 recordsLinked to original sources

PubMed2006

Decreased serum and red blood cell kynurenic acid levels in Alzheimer's disease.

Kynurenine aminotransferases (KAT I and KAT II) are responsible for the transamination of kynurenine (KYN) to form kynurenic acid (KYNA), an excitatory amino acid receptor antagonist. Since these members of the kynurenine pathway (KP) are proposed to be involved in the pathogenesis of Alzheimer's dementia (AD), the activities of these enzymes and the levels of these metabolites were measured in the plasma and red blood cells (RBCs) of AD and control subjects together with the inheritance of the apolipoprotein (APOE) epsilon4 allele. KYNA levels were significantly decreased both in the plasma and in the RBCs in AD, but the levels of KYN and the activities of KAT I and KAT II remained unchanged. No association has been found with the possession of the epsilon4 allele. These findings indicate an altered peripheral KP in AD regardless of the APOE status of the probands.

Aged↗

PubMed2006

Alterations of seizure-induced c-fos immunolabelling and gene expression in the rat cerebral cortex following dexamethasone treatment.

We examined the effects of dexamethasone on the expression of the inducible transcription factor c-fos in 4-aminopyridine (4-AP) seizures. Induction of c-fos mRNA due to 4-AP-elicited convulsion was detected by means of the polymerase chain reaction (PCR) in samples from the neocortex. Adult male rats were pretreated with different doses of dexamethasone (0.5, 1, 3, 5mg/kg body weight); 1h later 5mg/kg 4-AP was injected intraperitoneally. Controls received the solvent of dexamethasone. Pretreatment with dexamethasone provided significant symptomatic protection against 4-AP-induced convulsions. Immunohistochemistry was used to evaluate the presence of the c-fos protein. The number of Fos-immunoreactive nuclei per section area was measured in the neocortex and hippocampus. Pretreatment with dexamethasone resulted in a dose-dependent, significant decrease of seizure-induced Fos-protein immunoreactivity in the neocortex, in the hilum of the dentate fascia, as well as in regions CA1-3 of the hippocampus, compared to control animals. Brains processed for mRNA isolation and PCR, displayed a significant increase of c-fos mRNA following the 4-AP treatment, while pretreatment with dexamethasone did not prevent or decrease this boosted c-fos mRNA expression. We conclude that seizure-induced c-fos expression and intracellular Fos-protein localization are mediated by transmitter and receptor systems, and dexamethasone significantly decreases Fos immunoreactivity, probably by regulating the intracellular traffic of the protein. We also conclude that dexamethasone does not interfere with the genomic regulation of c-fos mRNA synthesis.

4-Aminopyridine↗

PubMed2006

APP mRNA splicing is upregulated in the brain of biglycan transgenic mice.

Many of the risk factors for cerebrovascular disease and atherosclerosis also increase the risk of Alzheimer's disease, characterized by the cerebral deposition of beta-amyloid plaques resulting from the abnormal processing of the transmembrane amyloid precursor protein (APP). The initiating event of cholesterol-induced atherosclerosis is the retention and accumulation of atherogenic apolipoprotein B (apoB) together with low-density lipoproteins in the vascular intima. Biglycan, a member of the small leucine-rich protein family, was suspected of contributing to this process. The individual and combined overexpressions of biglycan and apoB-100 were therefore examined on the cortical APP mRNA levels of transgenic mice by means of semiquantitative PCR. As compared with the control littermates, transgenic biglycan mice had significantly increased cortical APP695 (122%) and APP770 (157%) mRNA levels, while the double transgenic (apoB(+/-)xbiglycan(+/-)) mice did not exhibit any changes. These results provide the first experimental evidence that the atherogenic risk factor biglycan alters APP splicing and may participate in the pathogenesis of both Alzheimer and vascular dementias.

Amyloid beta-Protein Precursor↗

PubMed2006

Vernier threshold and the parallel visual pathways in bipolar disorder: a follow-up study.

Magnocellular (M) and parvocellular (P) visual pathways participate in the processing of low contrast and colors of objects, respectively. The aim of this study was to investigate M and P pathway functions in bipolar disorder during a depressive episode and after the amelioration of symptoms. Participants (17 patients with type I bipolar disorder and 20 matched healthy controls) received two vernier tasks. During the M pathway test, stimuli were dots with low luminance-contrast (5%), whereas during the P pathway test, isoluminant blue dots were presented against a yellow background. Participants were asked to detect the direction of the horizontal displacement of the dots (left or right). The assessment was performed during a depressive state and during a clinically improved state after 2 months. During the depressive state, the patients showed significantly impaired M and P pathway functions, whereas during the clinically improved state, their performance was better and was statistically indistinguishable from that of the controls. In conclusion, M and P pathways are impaired in depressed bipolar patients. This deficit is ameliorated along with clinical improvement. Further studies are necessary to separately assess cortical and precortical stages of information-processing, and to exclude the possibility of general motivational and attentional impairments.

Adult↗

PubMed2006

[The impact of mood alterations on creativity].

Basic elements of artistic (and other) creativity are the technical-professional skill and knowledge, the special talent and ability and the willingness or motivation; one of which being absent results in partially realised creativity like juvenile, frustrated or abandoned types, respectively. Psychometric scales have been developed to measure everyday and eminent creativity, which show that creativity correlates with higher psychoticism, impulsivity and venturesomeness scores and with lower neuroticism and conformity scores of the personality test employed in a general population. Among the psychological components of creativity are the cognitive processes, mood, motivation, and personality traits. Regarding mood, a theory of "inverted U" has been proposed as elevation of mood facilitates creativity to a certain point after what extreme increase has an adverse effect on achievement. Analysing psychopathology and creativity among various professions, higher rates of psychopathology, especially affective symptoms, have been found in art-related professions. Examples of immortal poets, writers, painters, sculptors and composers, having created invaluable cultural treasures for mankind, illustrate that many of them showed signs of mood alterations (unipolar or bipolar affective disorder spectrum) which were expressed in their artistic products.

Affect↗

PubMed2006

Recognition of complex mental states in patients with alcoholism after long-term abstinence.

AIMS: Previous studies demonstrated that patients with alcoholism display impaired emotional facial expression recognition even after long-term abstinence. These studies focused on basic emotions (happiness, anger, sadness, and disgust). In this study, we investigated the recognition of complex social emotions and mental states in patients with alcoholism after long-term abstinence and healthy control subjects. METHODS: Thirty patients with DSM-IV alcohol dependence and 30 age-matched, gender-matched, education-matched, and IQ-matched healthy control subjects participated. The patients were abstinent for >6 months. For the assessment of the recognition of complex social emotions and mental states, the Baron-Cohen Eyes Test was used. The experimenter presented 29 photographs of the eye-region of faces of actors and actresses on separate cards. Participants were asked to choose which of the four words (one target and three foils) best described the mental state of the actor/actress (for example, interested, doubtful, flirtatious, and insisting). The primary dependent measure was the number of correctly recognized stimuli. RESULTS: Patients with alcoholism correctly identified 22.4 (SD = 3.4) stimuli, whereas control participants identified 22.5 (SD = 2.9) stimuli. The difference was not statistically significant (P = 0.85). There was no significant difference in the proportion of patients and controls who correctly recognized each mental state. CONCLUSIONS: These results are against the hypotheses suggesting long-term adverse effects of alcohol on social cognition or supposing an inherent vulnerability of patients that may manifest before the development of alcohol dependence.

Adult↗

PubMed2006

Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes.

The aim of the present study was to investigate the oxidative status of lymphocytes from children (n=7) and adults (n=18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

Adolescent↗

PubMed2006

Abnormal neurological signs, visual contrast sensitivity, and the deficit syndrome of schizophrenia.

This study was designed to investigate the relationship between abnormal neurological signs, visual contrast sensitivity, and the deficit syndrome of schizophrenia. Visual contrast sensitivity for counterphase-modulated low spatial frequency gratings was measured in 32 non-deficit and 12 deficit schizophrenia patients and 20 healthy controls subjects. Abnormal neurological signs were evaluated with the Neurological Evaluation Scale (NES). Compared with the controls, patients with schizophrenia displayed impaired visual contrast sensitivity, which was associated with sensory integration deficits, as measured with the NES. The deficit syndrome was predicted by negative symptoms and sensory integration deficits. These results suggest that early-stage perceptual dysfunctions, which may reflect the abnormality of precortical magnocellular visual pathways, are related to a specific group of abnormal neurological signs.

Adult↗

PubMed2006

Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease.

Besides the genetic, biochemical and neuropathological analogies between Down's syndrome (DS) and Alzheimer's disease (AD), there is ample evidence of the involvement of oxidative stress (OS) in the pathogenesis of both disorders. The present paper reviews the publications on DS and AD in the past 10 years in light of the "gene dosage" and "two-hit" hypotheses, with regard to the alterations caused by OS in both the central nervous system and the periphery, and the main pipeline of antioxidant therapeutic strategies. OS occurs decades prior to the signature pathology and manifests as lipid, protein and DNA oxidation, and mitochondrial abnormalities. In clinical settings, the assessment of OS has traditionally been hampered by the use of assays that suffer from inherent problems related to specificity and/or sensitivity, which explains some of the conflicting results presented in this work. For DS, no scientifically proven diet or drug is yet available, and AD trials have not provided a satisfactory approach for the prevention of and therapy against OS, although most of them still need evidence-based confirmation. In the future, a balanced up-regulation of endogenous antioxidants, together with multiple exogenous antioxidant supplementation, may be expected to be one of the most promising treatment methods.

Alzheimer Disease↗

PubMed2006

Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis.

Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral beta-amyloid (Abeta) deposition in Alzheimer's disease (AD). The individual and combined effects of a high-cholesterol (HC) diet and the overexpression of the human apoB-100 gene were therefore examined on the cerebral expression and processing of APP in homozygous apoB-100 transgenic mice [Tg (apoB(+/+))], a validated model of atherosclerosis. When fed with 2% cholesterol for 17 weeks, only the wild-type mice exhibited significantly increased APP695 (123%) and APP770 (138%) mRNA levels in the cortex. The HC diet-induced hypercholesterolemia significantly increased the APP isoform levels in the membrane-bound fraction, not only in the wild-type animals (114%), but also in the Tg apoB(+/+) group (171%). The overexpression of human apoB-100 gene by the liver alone reduced the brain APP isoform levels in the membrane-bound fraction (78%), whereas the levels were increased by the combined effect of HC and the overexpression of the human apoB-100 gene (134%). The protein kinase C and beta-secretase protein levels were not altered by the individual or combined effects of these two factors. Our data indicate that the two atherogenic factors, the HC diet and the overexpression of the human apoB-100 gene by the liver, could exert different effects on the processing and expression of APP in the mice brain.

Amyloid Precursor Protein Secretases↗

PubMed2006

Correlations between clinical symptoms, working memory functions and structural brain abnormalities in men with schizophrenia.

Thirteen male patients with schizophrenia and thirteen male normal control subjects were compared by magnetic resonance imaging (MRI) on volumes of the straight gyrus (SG), anterior cingulate gyrus, middle frontal gyrus, hippocampus, third ventricle, cavum septi pellucidi, total brain volume and intracranial volume. In addition, neuropsychological tasks were used to measure working memory and executive functions. Healthy volunteers and schizophrenic patients showed no significant differences in mean values for volumes of regions of interests. In the case of the SG, we found a significant difference in laterality: the tendency toward left dominance in healthy volunteers changed to significant right dominance in patients. The schizophrenic patients showed lower performance in working memory tasks, and strongly significant group differences were observed in measures of neurological signs assessed by the Neurological Evaluation Scale (NES). Negative symptoms correlated with the level of spatial working memory and executive functions. Negative symptoms also correlated with the volume of the right hippocampus, while the rate of anhedonia negatively correlated with the relative volume of the left SG.

Adult↗

PubMed2006

3,4-Methylenedioxymethamphetamine (MDMA), but not morphine, alters APP processing in the rat brain.

The abuse of drugs such as opioids and 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') can have detrimental effects on the cognitive functions, but the exact molecular mechanism whereby these drugs promote neurodegeneration remains to be elucidated. The major purpose of the present pilot study was to determine whether the chronic in-vivo administration of morphine (10 mg/kg) or MDMA (1 mg/kg) to rats can alter the expression and processing of amyloid precursor protein (APP), the central molecule in the proposed pathomechanism of Alzheimer's disease. MDMA treatment significantly decreased the production of APP in the cytosolic fraction of the brain cortex. A concomitant 25% increase was found both in the beta-secretase (BACE) and APP mRNA levels (108%). In contrast, in the applied single dosage chronic morphine treatment did not influence either the APP and BACE protein levels or the APP mRNA production. These results indicate that the chronic use of 'ecstasy', but not morphine, may be harmful via a novel mode of action, i.e. by altering the APP expression and processing in the brain.

Amyloid Precursor Protein Secretases↗

PubMed2006

[Therapy of mental states at high risk for psychosis: preliminary results from Hungary].

INTRODUCTION: Recent evidence raised the possibility that low-dose antipsychotic treatment during the prodromal phase may prevent the development of full-blown psychosis. AIMS: To investigate the effectiveness of low-dose antipsychotic medication in the prevention of psychosis. METHODS: Fifty-two persons who fulfilled the PACE (Personal Assessment and Crisis Evaluation) criteria of ultra-high risk for psychosis participated in the study. Low-dose antipsychotic treatment (haloperidol or risperidone, 0.5-2 mg/day) was provided for 6 months together with psychoeducation and supportive psychotherapy. Participants were assessed at baseline, 6 months, and 12 months. Antidepressive therapy was provided as needed. RESULTS: Forty-two persons completed the study from whom 3 (7.1%) developed schizophrenia during the 6-month treatment period. New psychotic episodes were not observed during the 6-month follow-up period. Side effects were mild and transient, appearing in the first 4 weeks of treatment. The participants were satisfied with the treatment. CONCLUSIONS: Given that without a specific treatment, 30-60% of persons with ultra-high risk develop frank psychosis, low-dose antipsychotic treatment seems to be effective in the prevention or delay of psychosis.

Adult↗

PubMed2006

Development of visual motion perception in children of patients with schizophrenia and bipolar disorder: a follow-up study.

The "dorsal-stream vulnerability" hypothesis claims that motion-sensitive areas in the dorsal occipito-parietal visual system are vulnerable to genetic and environmental factors which affect brain maturation and development. The aim of this study was to investigate the possibility that developmental anomalies of directional motion perception can be detected in children of mothers with schizophrenia and bipolar disorder. Motion and form coherence thresholds were measured in 36 children of mothers with schizophrenia, 28 children of mothers with bipolar disorder, and 30 children with negative family history at 7, 8-9, and 10-11 years of age. These tasks require the detection of direction of coherently moving dots embedded among randomly oscillating dots (motion task) and the detection of tangentially oriented line-segments embedded among randomly oriented segments (form task). Results revealed that the rate of development in the motion task was less pronounced in children of mothers with schizophrenia than that in children of mothers with bipolar disorder and in age-matched controls. The development of form perception was spared. Children of mothers with bipolar disorder showed an intact development in both motion and form perception tasks. These results suggest that the progressive developmental abnormality of motion-sensitive visual areas may be a characteristic feature of schizophrenia-vulnerability.

Achievement↗

PubMed2006

Sensitivity to reward and punishment and the prefrontal cortex in major depression.

BACKGROUND: Patients with major depressive disorder (MDD) show neuropsychological impairments, including deficient executive functions and altered sensitivity to reward and punishment. METHODS: Executive functions (Wisconsin Card Sorting Test, WCST) and contingency learning based on the cumulative effect of reward and punishment (Iowa Gambling Test, IGT) were assessed in 30 medicated patients with unipolar MDD and in 20 healthy control volunteers. In the classic ABCD version of the IGT, advantageous decks are characterized by immediate small reward but even smaller future punishment. In the modified EFGH version, advantageous decks are characterized by immediate large punishment but even larger future reward. RESULTS: Patients with MDD were impaired in the WCST and in the ABCD version of the IGT but showed normal performances on the EFGH task. Depression, but not executive dysfunctions, significantly predicted performances on the EFGH task: less severe depressive symptoms were associated with better performances on the EFGH task. LIMITATIONS: The sample size was small and only few neuropsychological tests were used. Unmedicated patients were not assessed. Individual personality style, response strategies, and behavioral impulsivity were not investigated. CONCLUSIONS: Medicated patients with MDD show altered sensitivity to reward and punishment: immediate large reward enhanced related response patterns even when the strategy was disadvantageous and immediate large punishment did not prohibit related response patterns. Impairments in emotional decision-making were not a pure consequence of executive dysfunctions.

Adult↗

PubMed2006

Spatial frequency processing in schizophrenia: trait or state marker?

B. F. O'Donnell et al. found impaired discrimination performances at low and medium spatial frequencies in patients with schizophrenia. In this study, the authors replicated this finding in a group of remitted, unmedicated, and highly functioning outpatients with spared IQ and attentional functions. However, the deficit was restricted to low spatial frequencies (0.5 cycles/degree), which suggests that this deficit is a trait marker of schizophrenia.

Adult↗

PubMed2006

Spatiotemporal changes of the herpes simplex virus entry receptor nectin-1 in murine brain during postnatal development.

Herpes simplex virus (HSV) is known to replicate within the limbic system and to alter behavior in both humans and experimental animals. However, the reason why the virus selectively damages this anatomical, developmental, and functional neural unit remains a mystery. Nor is it known why herpes simplex encephalitis fails to respect these neuroanatomical boundaries in newborns. In the present study, the authors determined the spatiotemporal changes in the distribution of the major neural entry receptor for HSV (nectin-1) in postnatal mouse and rat brains. Discrete nectin-1 immunopositivity was observed in regions susceptible to HSV infection in specific developmental phases of central nervous system. The authors also describe nectin-1-related pathways controlling neuronal cell migration/brain morphogenesis, the disruption of which might lead to the emergence of mental disorders with a rapid cognitive decline.

Age Factors↗

PubMed2006

[Diagnosis and treatment of mental states at high risk for psychosis].

Despite the fact that the need for and possibility of diagnosing and treating schizophrenia in the prodromal phase is as old as the disease category itself. the first controlled studies were published only in the last 15 years. Using structured interviews and rating scales, the development/first episode of psychosis can be forecast only with a modest specificity: 30-60% of the persons with prodromal symptoms based on operationalised criteria develop full-blown psychosis during a 12-month follow-up period. A 6-month, low-dose antipsychotic treatment combined with psychotherapy can reduce this risk of psychosis by 50-60%. The treatment based on the clinical picture can be supplemented with antidepressants and anxiolytics. Despite the successful prevention, patients continue to show considerable residual symptoms and decreased coping abilities. Long-term effects of intervention, false positive cases, and stigmatization are among the most problematic, unresolved issues. According to international results and our own experience, psychosis prevention is currently adequate only in the case of help-seeking patients if the operationalised criteria of the prodrome are present. Detailed patient education and the ensuing informed consent are indispensable. Biological relatives of schizophrenia patients should be assessed with special care. Persons at increased risk of psychosis should be offered long-term follow-up and care and an "open doors" policy in the case of worsening symptoms and crisis.

Acute Disease↗