National Psychiatry Center

Budapest, Hungary

National Psychiatry Center

Budapest, Hungary

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Nagy H.,Semmelweis University | Nagy H.,National Institute for Medical Rehabilitation | Levy-Gigi E.,Rutgers University | Somlai Z.,Semmelweis University | And 4 more authors.
Neuropsychopharmacology | Year: 2012

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward. © 2012 American College of Neuropsychopharmacology. All rights reserved.


Somlai Z.,Semmelweis University | Moustafa A.A.,Rutgers University | Keri S.,National Psychiatry Center | Keri S.,University of Szeged | And 3 more authors.
Schizophrenia Research | Year: 2011

Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n = 40) performed similarly to healthy controls (n = 30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia. © 2010.


Szamosi A.,National Psychiatry Center | Levy-Gigi E.,National Psychiatry Center | Levy-Gigi E.,Rutgers University | Levy-Gigi E.,Haifa University | And 3 more authors.
Cortex | Year: 2013

When people perform an attentionally demanding target task at fixation, they also encode the surrounding visual environment, which serves as a context of the task. Here, we examined the role of the hippocampus in memory for target and context. Thirty-five patients with amnestic mild cognitive impairment (aMCI) and 35 healthy controls matched for age, gender, and education participated in the study. Participants completed visual letter detection and auditory tone discrimination target tasks, while also viewing a series of briefly presented urban and natural scenes. For the measurement of hippocampal and cerebral cortical volume, we utilized the FreeSurfer protocol using a Siemens Trio 3T scanner. Before the quantification of brain volumes, hippocampal atrophy was confirmed by visual inspection in each patient. Results revealed intact letter recall and tone discrimination performances in aMCI patients, whereas they showed severe impairments in the recognition of scenes presented together with the targets. Patients with aMCI showed bilaterally reduced hippocampal volumes, but intact cortical volume, as compared with the controls. In controls and in the whole sample, hippocampal volume was positively associated with scene recognition when a target task was present. This relationship was observed in both visual and auditory conditions. Scene recognition and target tasks were not associated with executive functions. These results suggest that the hippocampus plays an essential role in the formation of memory traces of the visual environment when people concurrently perform a target task at behaviorally relevant points in time. © 2012 Elsevier Ltd.


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.


Szily E.,Semmelweis University | Keri S.,University of Szeged | Keri S.,National Psychiatry Center
Clinical Psychology and Psychotherapy | Year: 2013

Evidence suggests that emotional processes play an important role in the development of delusions. The aim of the present study was to investigate emotion appraisal in individuals with high and low psychosis proneness. We compared 30 individuals who experienced a transient psychotic episode followed by a complete remission with 30 healthy control volunteers. The participants received the Peters et al. Delusion Inventory (PDI) and the Scherer's Emotion Appraisal Questionnaire. We also assessed the IQ and the severity of depressive and anxiety symptoms. Results revealed that individuals with high psychosis proneness displayed increased PDI scores and more pronounced anxiety compared with individuals with low psychosis proneness. There was a specific pattern of emotion appraisal in individuals with high psychosis proneness. In the case of fear, they achieved higher scores for external causality and immorality, and lower scores for coping ability and self-esteem compared with individuals with low proneness. The PDI scores were weakly related to external causality (r=0.41) and self-esteem (r=-0.37). In the case of sadness and joy, no emotion appraisal differences were found between participants with low and high proneness. These results suggest that individuals who had a history of psychotic breakdown and therefore exhibit high psychosis proneness display an altered appraisal of fear, emphasizing external circumstances, feeling less power to cope and experience low self-esteem. © 2011 John Wiley & Sons, 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.


Szily E.,Semmelweis University | Keri S.,University of Szeged | Keri S.,National Psychiatry Center
Journal of Neural Transmission | Year: 2012

The purpose of this study was to investigate the association between the G-703T polymorphism of the tryptophan hydroxylase 2 (TPH2) gene (rs4570625) and emotion appraisal in healthy volunteers. Participants were asked to recall a situation characterized by a strong emotion and to rate appraisal processes: novelty/expectation, pleasantness, goal-conduciveness, fairness, responsibility/ causation, coping ability, morality, and relationship to selfconcept. Results revealed that in the case of fear- and sadness-related autobiographical memories, participants with the GG genotype achieved higher appraisal scores for goal-conduciveness and lower scores for coping ability compared with participants with the TT genotype. In the case of joy, no differences were observed across genotypes. These results suggest that the TPH2 polymorphism affects appraisal processes in the case of negative emotions. © Springer-Verlag 2012.


Szamosi A.,National Psychiatry Center | Nagy H.,National Institute for Medical Rehabilitation | Nagy H.,Semmelweis University | Keri S.,National Psychiatry Center | Keri S.,University of Szeged
Neurodegenerative Diseases | Year: 2013

Background/Aims: α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson's disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD. Methods: Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (l-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software. Results: In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy. Conclusion: Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline. Copyright © 2012 S. Karger AG, Basel.

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