N. Domján

Different patterns of auditory information processing deficits in chronic schizophrenia and bipolar disorder with psychotic features

With the development of DSM-V and ICD-11 the definitions of psychiatric disorders are under re-evaluation. The emphasis is shifted from distinct disorders to clusters defined not only by symptomatology, but also by underlying neurobiology and cognitive deficits. Bipolar disorder I (BD-I) and schizophrenia (SZ) are of special interest since their differential diagnosis is often problematic and they partially overlap in measures ranging from genetics to neurophysiology. Event-related potentials (ERPs) are one of the most studied factors but the results are still controversial, primarily in BD-I, where ERPs reflecting different stages of auditory information processing have been much less investigated. In this study, we aimed at investigating the changes of five auditory event-related potentials (P50 and N100 suppression, duration and pitch deviant mismatch negativity (MMN) and P3b) in 20 SZ and 20 BD-I patients with a history of psychosis and 21 healthy control subjects. Our data revealed substantial differences between the two patient groups. Only patients with SZ demonstrated impaired N100 suppression, shorter duration deviant MMN latency and attenuated P3b amplitude, while prolonged pitch deviant MMN latency was found to be characteristic of the BD-I group. No shared ERP abnormalities were observed among the patient groups. Our results indicate that SZ and BD-I are characterized by highly different neurophysiological profiles when measured in the same laboratory setting.

Preserved intention maintenance and impaired execution of prospective memory responses in schizophrenia: evidence from an event-based prospective memory study

Executive system dysfunction and impaired prospective memory (PM) are widely documented in schizophrenia. However, it is not yet clarified which components of PM function are impaired in this disorder. Two plausible target components are the maintenance of delayed intentions and the execution of PM responses. Furthermore, it is debated whether the impaired performance on frequently used executive tasks is associated with deficit in PM functions. The aim of our study was twofold. First, we aimed to investigate the specific processes involved in event-based PM function, mainly focusing on difference between maintenance of intention and execution of PM responses. Second, we aimed to unfold the possible connections between executive functions, clinical symptoms, and PM performance. An event-based PM paradigm was applied with three main conditions: baseline (with no expectation of PM stimuli, and without PM stimuli), expectation condition (participants were told that PM stimuli might occur, though none actually did), and execution condition (participants were told that PM stimuli might occur, and PM stimuli did occur). This procedure allowed us to separately investigate performances associated with intention maintenance and execution of PM responses. We assessed working memory and set-shifting executive functions by memory span tasks and by the Wisconsin Card Sorting Test (WCST), respectively. Twenty patients diagnosed with schizophrenia and 20 healthy control subjects (matched according to age and education) took part in the study. It was hypothesized that patients would manifest different levels of performance in the expectation and execution conditions of the PM task. Our results confirmed that the difference between baseline performance and performance in the execution condition (execution cost) was significantly larger for participants diagnosed with schizophrenia in comparison with matched healthy control group. However, this difference was not observed in the expectation condition. The PM performance in the execution condition was correlated with impaired executive functions in schizophrenia. Specifically, the size of execution cost positively correlated with percent of perseverative errors committed on WCST by the patient group. Our results suggest that maintenance of delayed intentions is unimpaired in schizophrenia, whereas the impairment in execution of PM responses is associated with set-shifting deficit.

A New Division of Schizophrenia Revealed Expanded Bilateral Brain Structural Abnormalities of the Association Cortices

The phenomenological and, consequently, pathophysiological heterogeneity of schizophrenia may be substantially decreased by determining etiologically valid subgroups. In a cross-sectional study, we analyzed the brain structural impairments of outpatients with schizophrenia using concurrent subgrouping methods, partly to enhance the extensity of exploration, and partly to estimate the validation of the divisions. High resolution T1-weighted MR images were obtained for 21 patients and 13 healthy controls. Localized gray matter volumetric deficits were defined with optimized voxel-based morphometry. Employing two concurrent methods (i.e., the widely known deficit-non-deficit division vs. the neurocognitive clusters we identified earlier) the patient group was iteratively divided into two subgroups, and their volumetric peculiarities were compared with one another and with healthy controls. Our division revealed more significant differences demonstrating bilateral brain structural deficits, which affected the association cortices, primarily the heteromodal fields and partly the unimodal fields. This is the first study that showed that abnormalities of the association cortices can be bihemispherial and expanded in schizophrenia, even in the cases of outpatients living integrated in society. Our result suggests that the extended association cortex abnormalities could constitute substantial and determining neurological substrates in the phenomenology and aetiopathogenesis of schizophrenia, at least in a subgroup of patients with more unfavorable neurocognitive characteristics.

Extended Bihemispherial Impairments of the Association Cortices Were Revealed in Outpatients with Schizophrenia by a New Subgrouping Method

Introduction To clarify pathophysiology of schizophrenia it is required to decrease the phenomenological heterogeneity, and one of the possible ways is determining neurobiologically valid subgroups. Objectives Employing two concurrent methods – Deficit and Nondeficit (Carpenter et al., 1988) vs. cluster S and Z (Szendi et al., 2010) – the group of patients was divided into two subgroups, and brain volumetric peculiarities of the whole mixed group of patients and of these subgroups were compared with the healthy controls and each other. Aims This study aims to possibly reveal the most brain structural anomalies by applying concurrent subgrouping methods of patients, and moreover to confront their validity by the results. Methods High resolution T1 weighted images were performed on n=21 patients with schizophrenia, living integrated in the society and treated in outpatient care, and n=13 healthy control persons. Localised grey matter volumetric deficits were defined with optimised voxel-based morphometry. Results Most areas were revealed in the case of the cluster S, which was characterised by an expansive, bilateral brain structural impairment, which mainly affected the heteromodal and partly the unimodal association cortices. Conclusions This suggests that the expansive impairment of the association cortices could have a determining role in the etiopathogenesis of the unfavourable cluster of patients with schizophrenia. In the literature, an extent of damage commensurable to our observations specifically on association areas has never been detected – and our systematic neurocognitive subgrouping method provided the possibility for this. Financial support for the research was provided by KTIA_NAP_13-2-2014-0020 to Mihaly Racsmany.

Double Dissociation of Explicit and Implicit Learning Performances in Neurocognitive Subgroups of Schizophrenia

Introduction Mapping cognitive functions in schizophrenia is important for approaching the etiological background of the disease. Objectives To examine the explicit and the implicit learning processes with experimental psychological methods in neurocognitive subgroups identified by us earlier (Szendi et al, 2010). Aims To find substantial cognitive differences between the neurocognitive subgroups Methods Patients with schizophrenia (n=19) and matched healthy control persons (n=11) participated in the study. The patients were recruited randomly from the patient pool which constitued the subject base for the original clustering process, we enrolled n=9 patients from the cluster S, and n=10 from the cluster Z. Besides the comprehensive neuropsychiatric assessment, the explicit learning performances were tested by a verbal learning task, while the implicit learning by the Alternating Serial Reaction Time Task. Results While the whole group of patients did not differ from the healthy persons regarding either the explicit or the implicit memory tasks, the performances of the two subgroups of patients showed a double dissociation in these tasks. Whereas patients belonging to cluster S could recall significantly less words in the explicit cued recall test after the word-list learning than patients in cluster Z (and the healthy persons), the performance of patients in cluster Z in the implicit sequence-specific learning fell behind the cluster S (and the healthy group). Conclusions The double dissociation of explicit and implicit memorys impairments suggests that the neurocognitive background of the two subgroups of schizophrenia (S vs Z) might substantially differ from each other. Financial support: KTIA_NAP_13-2-2014-0020

Tau haplotypes and ApoE4 do not act in synergy on Alzheimer's disease

There are conflicting results regarding the role of tau (MAPT) haplotypes in neurodegenerative disorders. Recent reports suggest that ethnicity factors and gene-gene interactions may influence the risk of developing Alzheimers disease (AD). The present study investigates possible synergism between MAPT haplotype and ApoE state in Hungarian Caucasian AD cases (n=91) and control (n=83) population. The difference in MAPT H1 allele frequency did not reach significant level in AD (78%), and control individuals (73.5%), however ApoE4 carriers were significantly overrepresented in AD (34.1% vs. 20%) compared to the control population. Though a specific combination of ApoE4 and H1 alleles were found to be associated to AD (14.5% vs. 30.8%), synergistic genetic interaction could not be inferred. Our findings support the notion that while ApoE4 might be involved in AD pathology the MAPT H1 allele neither associates nor interacts through an epistasis with ApoE4 in the development of the disease.

PW01-215 - Connections between trait anxiety and the mechanisms of decision making in alcohol dependence

Objectives According to recent studies anxiety has a significant impact on cognitive functioning, especially on decision-making. Alcohol dependent patients (ADP) achieve worse performance on decision-making simulation tasks compared to healthy controls. Our aim was to investigate how trait anxiety is connected to decision-making mechanisms in ADP. Methods The data of 76 ADP have been analyzed. To examine decision-making mechanisms we used the “ABCD” version of the Iowa Gambling Task (IGT). The IGT total score was calculated and we divided the task into 5 equal blocks to study the pattern of the decision-making process. We administered the Spielberger Trait Anxiety Inventory (STAI) and the Wechsler Adult Intelligence Scale. The patient group was arranged into two subgroups with median split method based on the STAI scores. One group (N=38) was characterized by low trait anxiety level, and the other (N=38) had high level of trait anxiety. For comparing the two groups’ decision-making mechanisms we used independent samples t-test. Results The group with higher level of trait anxiety performed significantly poorer on the IGT (t=2.09, p=0.04). The detailed analysis of the two groups’ decision-making mechanisms showed that the difference between the groups became significant in the 5th block (t=2.57, p=0.01). Conclusions Decision-making deficit is not homogenous in the ADP group, as according to our results the trait anxiety level influences the adequacy of decision-making. Psycho-biological background of the inadequate decision-making needs further investigation and this knowledge could be used in the future to improve decision-making mechanisms of the ADP.

P03-136 Gamma band response during auditory information processing in schizophrenia

Aims In the present study we investigated the correlation between evoked gamma activity and P50 suppression and between induced gamma activity and P300 amplitude on one schizophrenic population. These kind of auditory processing impairments are substantial in schizophrenia. Methods Thirty-one patients with schizophrenia and twenty-one controls were involved. Electroencephalogram was recorded with 19 Zn electrodes, which were placed according to the international 10-20 system. Results P50 suppression was significantly reduced in schizophrenic patients (F(1,53)=9.89, p=0.03). There was a not significant reduction in the early evoked gamma response. Furthermore, we found no correlation between P50 amplitudes and gamma amplitude for the first stimulus in neither groups, while there was a significant correlation for the second click in the control group (R=0.43, p=0.03 for controls, R=0.18, p=0.30 for patients). The amplitude of the P300 auditory evoked potential was significantly reduced at Pz electrode in schizophrenic patients (F(1,53)=11.91, p=0.01). Induced gamma response around the peak P300 latency was diminished in the patient group (F(1,53)=11.12, p=0.002). There was no correlation between P300 amplitudes and gamma amplitude in neither group. Conclusion According to our results evoked and induced gamma activity is differentially affected in schizophrenia during auditory information processing. The absence of late induced gamma response during target stimulus detection among patients might reflect abnormal functional connectivity between different cortical areas, and result in inefficient integration and utilization of sensory stimuli.