National Psychiatry Center

Budapest, Hungary

National Psychiatry Center

Budapest, Hungary
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Keri S.,University of Szeged | Keri S.,National Psychiatry Center | Benedek G.,University of Szeged
Neuroscience | Year: 2011

Fragile X syndrome (FXS) is characterized by the impairment of the magnocellular/dorsal visual system. In this study, we explored how fragile X protein (FMRP) expression may affect visual functions in healthy participants. The percentage of FMRP-positive lymphocytes was measured using a rapid antibody test in blood smears of 100 male volunteers. CGG triplet expansion was also determined. Results revealed that participants with fewer FMRP-positive lymphocytes exhibited lower performances on tests biasing information processing toward the magnocellular pathway and dorsal visual stream (contrast sensitivity at low spatial/high temporal frequency and motion coherence). It was not observed in the case of tests biasing information processing toward the parvocellular pathway and ventral stream (contrast sensitivity at high spatial/low temporal frequency and form coherence). These results suggest that healthy persons with lower peripheral FMRP expression display a visual phenotype similar to that described in patients with FXS. © 2011 IBRO.

Levy-Gigi E.,National Psychiatry Center | Levy-Gigi E.,Haifa University | Szabo C.,National Psychiatry Center | Kelemen O.,Bacs Kiskun County Hospital | And 3 more authors.
Biological Psychiatry | Year: 2013

Background Posttraumatic stress disorder (PTSD) is characterized by a reduced expression of FKBP5, a key modulator of the glucocorticoid receptor. Smaller hippocampal volume has also been documented in PTSD. We explored possible changes in FKBP5 gene expression and brain structure in patients with PTSD after cognitive behavioral therapy (CBT). Methods We measured peripheral FKBP5 RNA and volumes of the hippocampus, amygdala, and medial orbitofrontal cortex in 39 patients with PTSD before and after CBT. The control subjects were 31 trauma-exposed individuals without PTSD who were also assessed twice. Gene expression changes were screened with a microarray toolkit, which was followed by quantitative polymerase chain reaction for FKBP5 RNA. Brain volumes were measured using FreeSurfer. Results At baseline, patients with PTSD showed lower FKBP5 gene expression and smaller hippocampal and medial orbitofrontal cortex, but not amygdala, volumes relative to control subjects. At follow-up, we found significantly increased FKBP5 expression and increased hippocampal volume in patients with PTSD. At follow-up, patients did not differ from control subjects in hippocampal volume. Improvement in PTSD symptoms was predicted by increased FKBP5 expression and increased hippocampal volume, but the primary predictor was FKBP5 expression. The most significantly altered gene expression in patients with PTSD relative to control subjects was found for ribosomal protein S6 kinase, which did not change after CBT and did not correlate with hippocampal volume. Conclusions Clinical improvement in individuals with PTSD was associated with increased expression of FKBP5 and increased hippocampal volume, which were positively correlated. © 2013 Published by Elsevier Inc.

Keri S.,National Psychiatry Center | Keri S.,University of Szeged | Szamosi A.,National Psychiatry Center | Benedek G.,University of Szeged | Kelemen O.,Bacs Kiskun County Hospital
Neuropsychologia | Year: 2012

Paired associates learning is impaired in both schizophrenia and amnestic mild cognitive impairment (aMCI), which may reflect hippocampal pathology. In addition, schizophrenia is characterized by the dysfunction of the retino-geniculo-striatal magnocellular (M) visual pathway. The purpose of this study was to investigate the interaction between visual perceptual and memory dysfunctions. We administered a modified version of the CANTAB paired associates learning task to patients with schizophrenia (n=20), aMCI (n=20), and two groups of matched healthy controls (n=20 for each patient group). The stimuli in the paired associates learning task biased information processing toward the M pathways (low contrast, low spatial frequency) and parvocellular (P) pathways (high contrast, high spatial frequency). Results revealed that patients with schizophrenia exhibited a more pronounced learning deficit for M-biased relative to P-biased stimuli. In aMCI, there were similar memory deficits for both types of stimuli. Orientation discrimination for M- and P-biased stimuli was intact in both groups of patients. The number of errors in the M-biased memory condition significantly and inversely correlated with the volume of the right hippocampus in schizophrenia. These results suggest an interaction between M-biased perceptual processing and short-term relational memory in schizophrenia, which may be associated with the structural alteration of the right hippocampus. © 2012 Elsevier Ltd.

Keri S.,University of Szeged | Keri S.,National Psychiatry Center | Benedek G.,University of Szeged
Neuroscience | Year: 2012

Dysfunctions of the geniculo-striatal magnocellular (M) visual pathway and its cortical recipients have been documented in fragile X syndrome and in FMR1 premutation carriers. However, the mechanism of this impairment is less clear. To elucidate this issue, we completed the measurement of visual functions at different stages of information processing: low-level mechanisms (contrast sensitivity biasing information processing toward the M and parvocellular [P] pathways), primary visual cortex (motion-defined and static Vernier threshold), and higher-level form and motion processing (coherence thresholds). Results revealed that FMR1 premutation carriers, relative to non-carrier controls, exhibited lower contrast sensitivity for M pathway-biased stimuli, higher Vernier threshold for motion-defined stimuli, and higher global motion coherence threshold. Although both elevated FMR1 mRNA and reduced fragile X mental retardation protein (FMRP) levels were associated with impaired visual functions, regression analysis indicated that FMRP was the primary factor. In premutation carriers, a toxic gain-of-function of elevated FMR1 mRNA has been suggested, whereas reduced FMRP is linked to neurodevelopmental aspects. Here, we showed that FMRP may the primary factor associated with visual dysfunctions. © 2012 IBRO.

Kiss I.,National Psychiatry Center | Levy-Gigi E.,Rutgers University | Keri S.,National Psychiatry Center | Keri S.,University of Szeged
Biological Psychology | Year: 2011

Oxytocin plays an important role in human attachment, trust, social perception, memory, and fear regulation. Evidence suggests that CD38, a regulator of oxytocin release, may also be critical in these processes. The purpose of this study was to investigate the predictors of plasma oxytocin level measured after a task requiring intimate trust (secret sharing), modeling psychotherapeutic processes, and a neutral social interaction. Results revealed that peripheral CD38 expression positively predicted both trust-related and trust-unrelated oxytocin levels. In addition, habituation of arousal, as measured by skin conductance response, and attachment anxiety also emerged as predictors of oxytocin level in the trust-related condition. These results suggest that CD38 plays a general role in oxytocin secretion, whereas habituation of arousal and attachment anxiety are specifically related to situations involving intimate trust. © 2011 Elsevier B.V.

Keri S.,University of Szeged | Kiss I.,National Psychiatry Center
Physiology and Behavior | Year: 2011

Oxytocin may be implicated in various sophisticated human processes, including attachment, trust, social perception, memory, and fear regulation. In this study, we explored the relationship between plasma oxytocin level measured after a task requiring intimate trust (secret sharing) and habituation of autonomic arousal (skin conductance response) in sixty healthy volunteers. Results revealed that oxytocin was elevated in the trust-related condition relative to a neutral baseline. In a cognitive stress condition (mental arithmetic task), there was no significant oxytocin elevation relative to the neutral condition. After controlling for age, gender, education, state anxiety and depression, we found a significant positive relationship between trust-related oxytocin level and habituation of autonomic arousal. This relationship was absent in the case of neutral (trust-unrelated) oxytocin level. These results suggest that the habituation of autonomic arousal is closely related to oxytocin released during trust-related social interactions. © 2010 Elsevier Inc.

Levy-Gigi E.,Rutgers University | Levy-Gigi E.,National Psychiatry Center | Keri S.,National Psychiatry Center | Keri S.,University of Szeged
PLoS ONE | Year: 2012

Spontaneous encoding of the visual environment depends on the behavioral relevance of the task performed simultaneously. If participants identify target letters or auditory tones while viewing a series of briefly presented natural and urban scenes, they demonstrate effective scene recognition only when a target, but not a behaviorally irrelevant distractor, appears together with the scene. Here, we show that individuals with posttraumatic stress disorder (PTSD), who witnessed the red sludge disaster in Hungary, show the opposite pattern of performance: enhanced recognition of scenes presented together with distractors and deficient recognition of scenes presented with targets. The recognition of trauma-related and neutral scenes was not different in individuals with PTSD. We found a positive correlation between memory for scenes presented with auditory distractors and re-experiencing symptoms (memory intrusions and flashbacks). These results suggest that abnormal encoding of visual scenes at behaviorally irrelevant events might be associated with intrusive experiences by disrupting the flow of time. © 2012 Levy-Gigi, Kéri.

Kovacs T.,National Psychiatry Center | Kelemen O.,Bacs Kiskun County Hospital | Keri S.,National Psychiatry Center | Keri S.,University of Szeged
Psychiatry Research | Year: 2013

The purpose of this study was to investigate Fragile X Syndrome (FXS)-related mechanisms in schizophrenia, including CGG triplet expansion, FMR1 mRNA, and fragile X mental retardation protein (FMRP) levels in lymphocytes. We investigated 36 patients with schizophrenia and 30 healthy controls using Southern blot analysis, mRNA assay, and enzyme-linked immunosorbent assay (ELISA). General intellectual functions were assessed with the Wechsler Adult Intelligence Scale-III, and the clinical symptoms were evaluated with the Positive and Negative Syndrome Scale. Results revealed that, relative to healthy controls, CGG triplet size and FMR1 mRNA were unaltered in patients with schizophrenia. However, the FMRP level was significantly reduced in patients compared with controls. We found an association between lower FMRP levels, reduced IQ, and earlier illness onset in schizophrenia. Chlorpromazine-equivalent antipsychotic dose did not correlate with FMRP levels. These results raise the possibility of impaired translation of FMR1 mRNA, altered epigenetic regulation, or increased degradation of FMRP in schizophrenia, which may play a role in dysfunctional neurodevelopmental processes and impaired neuroplasticity. © 2012 Elsevier Ireland Ltd.

Szamosi A.,National Psychiatry Center | Kelemen O.,Bacs Kiskun County Hospital | Keri S.,National Psychiatry Center | Keri S.,University of Szeged
Journal of Psychiatric Research | Year: 2012

Objective: The phosphoinositide 3'-kinase (PI3K) - protein kinase B (AKT1) - glycogen synthase kinase (GSK)-3β system is modulated by several factors implicated in the pathophysiology of schizophrenia. Evidence suggests that neuregulin 1 (NRG1) induces decreased AKT phosphorylation in schizophrenia relative to healthy controls, which may be related to dysfunctional neurodevelopment and neuroplasticity. The aim of this study was to investigate the relationship between NRG1 - induced AKT phosphorylation and hippocampal volume in schizophrenia. Methods: Participants were 20 first-episode patients with schizophrenia who did not receive psychotropic medications and 20 matched healthy controls. We measured the phosphorylated AKT - total AKT and phosphorylated ERK (extracellular signal-regulated kinase) - total ERK ratios in peripheral lymphoblasts before and after NRG1 administration. Whole-brain, left, and right hippocampal volumes were quantified using FreeSurfer software. Results: Patients with schizophrenia displayed decreased AKT but normal ERK ratio compared with controls. Patients also had a reduction in left hippocampal volume. There was no significant difference between patients and controls in whole-brain and right hippocampal volume. Decreased AKT ratio was associated with reduced hippocampal volume. There was no significant relationship between ERK ratio and brain structure. Conclusion: Activation of the AKT system is specifically associated with hippocampal volume in first-episode schizophrenia, which provides further evidence for the pivotal role of this messenger system in the pathophysiology of psychotic disorders. © 2011 Elsevier Ltd.

Balog Z.,National Psychiatry Center | Kiss I.,National Psychiatry Center | Keri S.,University of Szeged | Keri S.,National Psychiatry Center
Genes, Brain and Behavior | Year: 2011

ZNF804A, encoding the transcription factor zinc-finger protein 804A, is a genome-wide supported psychosis gene associated with schizophrenia and bipolar disorder. However, only little information is available on the role of ZNF804A regarding the cognitive phenotype of psychosis. In this study, we investigated the relationship between the single-nucleotide polymorphism rs1344706 (A/C, A = risk allele) in ZNF804A and attention in 200 healthy volunteers. We used the attention network test, which was designed to separate the three main components of attention (alerting, orienting and executive control). Results showed a significant association with the executive control network: the A/A genotype and the A-allele were associated with increased reaction time when conflicting information was present. In contrast, rs1344706 was not related to alerting and orienting. These results suggest that the genome-wide supported psychosis risk variant of ZNF804A is associated with altered executive control (larger conflict effect), which is a potential endophenotype of psychotic disorders. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

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