The Actigraphy-Based Identification of Premorbid Latent Liability of Schizophrenia and Bipolar Disorder.

(1) Background and Goal: Several studies have investigated the association of sleep, diurnal patterns, and circadian rhythms with the presence and with the risk states of mental illnesses such as schizophrenia and bipolar disorder. The goal of our study was to examine actigraphic measures to identify features that can be extracted from them so that a machine learning model can detect premorbid latent liabilities for schizotypy and bipolarity. (2) Methods: Our team developed a small wrist-worn measurement device that collects and identifies actigraphic data based on an accelerometer. The sensors were used by carefully selected healthy participants who were divided into three groups: Control Group (C), Cyclothymia Factor Group (CFG), and Positive Schizotypy Factor Group (PSF). From the data they collected, our team performed data cleaning operations and then used the extracted metrics to generate the feature combinations deemed most effective, along with three machine learning algorithms for categorization. (3) Results: By conducting the training, we were able to identify a set of mildly correlated traits and their order of importance based on the Shapley value that had the greatest impact on the detection of bipolarity and schizotypy according to the logistic regression, Light Gradient Boost, and Random Forest algorithms. (4) Conclusions: These results were successfully compared to the results of other researchers; we had a similar differentiation in features used by others, and successfully developed new ones that might be a good complement for further research. In the future, identifying these traits may help us identify people at risk from mental disorders early in a cost-effective, automated way.

[Role of music activities in psychiatric rehabilitation].

INTRODUCTION: In Hungary, the use of music in rehabilitation is a scarcely researched area. In this study we aimed to examine the structure, purpose, and role of music activities conducted at the Department of Psychiatry, University of Szeged. We studied the rehabilitation programs of psychiatric patients and the role of music activities in healing and reintegration. All of this has been compared to the structure, timing and effectiveness of music therapy methods used worldwide. METHODS: The 10-person sample consisted of patients participating in the rehabilitation program of the department, who agreed to attend music sessions there over a two-week interval. During the first and last interventions, we mea - sured patient satisfaction with life, perceived social support, and levels of depression and trait anxiety. In addition, we measured changes in anxiety during a single music session, and a short structured interview was completed with each patient at the time of the last session. RESULTS: Our results show that patients' perceived social support increased (t[9]=-3,61, p< 0,01) during the intervention period - especially regarding the family dimension (t[9]=-2,57 , p=0,03). The level of anxiety decreased (t[9]=2,42, p=0,03), and the level of depression also showed a marginally significant decrease (t[9]=2,11, p= 0,06). No significant differences were found in the changes of life satisfaction and the immediate anxiety-relieving effect of music practice. The content of the interviews however confirmed that there is indeed an immediate anxiety-relieving effect of a single music session. DISCUSSION: To summarise the quantitative and qualitative data, it can be stated that the music activities of the department are several points in line with the international practice, and operate with low risk and high efficiency. The work done here has confirmed that music activities can be an effective method along with the clinical treatments and play an important role in the rehabilitation process.

[SHIFTING FUNCTION OF WORKING MEMORY IN PSYCHOTIC DISORDERS]. / A MUNKAMEMÓRIA VÁLTÁSI FUNKCIÓJA PSZICHOTIKUS KÓRKÉPEKBEN.

BACKGROUND AND AIMS: Mental disorders with psychotic features are overlapping in many ways and there are a growing number of comparative studies in the last decades regarding this. Cognitive deficit is well underpinned in schizophrenia, but fewer studies are conducted in this area including patients with bipolar affective disorder. Therefore the aim of the present study was to investigate the cognitive performance of these two patient groups and healthy controls. The Wisconsin Card Sorting Task is a very sensitive measure of the shifting function. Schizophrenic patients perform consistently poorer on this task than healthy controls, while there are not much data about individuals with bipolar affective disorder. METHODS: The Wisconsin Card Sorting Task and clinical symptom rating scales were administered to 26 patients with schizophrenia, 24 with bipolar affective disorder and 21 healthy controls. RESULTS: Significant differences were found among the performance of the three groups using four different dimensions of the Wisconsin Card Sorting Task. The schizophrenic group made more perseverative errors and achieved less conceptual level responses and completed fewer categories compared to healthy controls. Patients with schizophrenia were able to complete fewer categories and had fewer conceptual level responses than the bipolar group. No significant differences were observed between patients with bipolar disorder and healthy controls. CONCLUSIONS: According to these results, patients with schizophrenia and bipolar affective disorder showed no similarities on the Wisconsin Card Sorting Task. Bipolar patients performed the task on the same level as healthy individuals did. The two mental disorders influence cognitive performance differently.

[Delirium: a common complication of severe pathological conditions]. / Delírium: a súlyos kórállapotok közönséges szövodménye.

Delirium is a complex syndrome caused most often by secondary neuronal dysfuncions due to systemic disorders. Because of the central nervous system manifestations of the general disease processes that are getting through the blood-brain barrier, the vigilance of attention flucutates and, therefore, the integration of incoming stimuli fails - resulting in inadequate behavioral answers. Delirium is one of the most common and serious complications of diseases, particularly in the elderly and patients in critical state. It cannot be traced back to a single etiologic process; one should consider all those pathophysiologic mechanisms that are interacting with one another simultaneously impairing the integrated functioning of the brain. Despite the high prevalence rate of delirium and the marked adverse effects on the outcome of the underlying disorders, management and therapy are basically lacking professional guidelines. The syndrome is a threatening state, requiring increased clinical attention and often intensive care. Beside evidence based therapeutic methods, conscious, targeted screening of the known risk factors and measures against them when they present themselves may exert remarkable influence on the prevention of delirium, which is also an exceptionally important aspect of the care of patients in critical state.

Hierarchical organization of human physical activity.

Human physical activity (HPA), a fundamental physiological signal characteristic of bodily motion is of rapidly growing interest in multidisciplinary research. Here we report the existence of hitherto unidentified hierarchical levels in the temporal organization of HPA on the ultradian scale: on the minute's scale, passive periods are followed by activity bursts of similar intensity ('quanta') that are organized into superstructures on the hours- and on the daily scale. The time course of HPA can be considered a stochastic, quasi-binary process, where quanta, assigned to task-oriented actions are organized into work packages on higher levels of hierarchy. In order to grasp the essence of this complex dynamic behaviour, we established a stochastic mathematical model which could reproduce the main statistical features of real activity time series. The results are expected to provide important data for developing novel behavioural models and advancing the diagnostics of neurological or psychiatric diseases.

Brain Derived Neurotrophic Factor and Cognitive Dysfunction in the Schizophrenia-Bipolar Spectrum: A Systematic Review and Meta-Analysis.

Background: Cognitive impairment is a core feature of disorders on the schizophrenia-bipolar spectrum, i.e., schizophrenia, bipolar disorder, and schizoaffective disorder. Brain-derived neurotrophic factor (BDNF) has been proposed to be a biomarker of cognitive impairment in these disorders as it plays a critical role in neuroplasticity and proposed to mediate some of the psychotropic effects of medication. However, despite numerous studies investigating the association between circulating BDNF and these disorders, no solid conclusions have been drawn regarding its involvement in cognitive impairment. Objectives: The current systematic review and meta-analysis aims to examine blood BDNF levels and cognitive dysfunction in patients on the schizophrenia-bipolar spectrum as well as to evaluate whether circulating BDNF measurements can act as a biomarker for cognitive dysfunction. Methods: Studies were identified by searching Embase and Medline databases for English language articles published in peer-reviewed journals between 2000 January and 2021 June according to the PRISMA guidelines. A total of 815 articles were identified of which 32 met the inclusion criteria for the systematic review - reporting on comparisons between blood BDNF levels and cognitive functions of schizophrenia or bipolar disorder patients versus healthy controls (no studies involving schizoaffective patients were specifically obtained for the time being). Twenty-four of these studies (19 with schizophrenia and 5 with bipolar disorder patients) were eligible to be included in the meta-analysis. Results: Our findings indicated that circulating BDNF levels were significantly reduced in patients experiencing an acute episode of schizophrenia or bipolar disorder compared to healthy controls. Cognitive function was also found to be significantly worse in patients, however, correlations between BDNF levels and cognitive impairment were not always detected. Interventions, especially pharmacotherapy seemed to improve certain aspects of cognition and increase circulating BDNF levels. Conclusion: Circulating BDNF alone does not seem to be a valid biomarker of cognitive dysfunction in patients with disorders on the schizophrenia-bipolar spectrum, owing to several confounding factors. Changes of the circulating levels of BDNF should be evaluated in a wider context of other stress-, immune-, and inflammatory-related factors.

Detailed analysis and comparison of different activity metrics.

Actigraphic measurements are an important part of research in different disciplines, yet the procedure of determining activity values is unexpectedly not standardized in the literature. Although the measured raw acceleration signal can be diversely processed, and then the activity values can be calculated by different activity calculation methods, the documentations of them are generally incomplete or vary by manufacturer. These numerous activity metrics may require different types of preprocessing of the acceleration signal. For example, digital filtering of the acceleration signals can have various parameters; moreover, both the filter and the activity metrics can also be applied per axis or on the magnitudes of the acceleration vector. Level crossing-based activity metrics also depend on threshold level values, yet the determination of their exact values is unclear as well. Due to the serious inconsistency of determining activity values, we created a detailed and comprehensive comparison of the different available activity calculation procedures because, up to the present, it was lacking in the literature. We assessed the different methods by analysing the triaxial acceleration signals measured during a 10-day movement of 42 subjects. We calculated 148 different activity signals for each subject's movement using the combinations of various types of preprocessing and 7 different activity metrics applied on both axial and magnitude data. We determined the strength of the linear relationship between the metrics by correlation analysis, while we also examined the effects of the preprocessing steps. Moreover, we established that the standard deviation of the data series can be used as an appropriate, adaptive and generalized threshold level for the level intersection-based metrics. On the basis of these results, our work also serves as a general guide on how to proceed if one wants to determine activity from the raw acceleration data. All of the analysed raw acceleration signals are also publicly available.

Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping.

The description of the heterogeneous phenomenological, pathophysiological, and etiological nature of schizophrenia is under way; however, the relationships between heterogeneity levels are still unclear. We performed a robust cross-sectional study, including a systematic neuropsychological battery, assessment of clinical symptoms, neurological soft signs, morphogenetic anomalies and smell identification, and measurement of event-related potentials on 50 outpatients with schizophrenia in their compensated states. An explorative fuzzy cluster analysis revealed two subgroups in this sample that could be distinguished from each other on symptomatological, cognitive and neurological levels. The patterns of cognitive dysfunctions and neurological developmental anomalies equally indicate that there may be hemispherical differences between the patients belonging to the different clusters.

Disrupted memory inhibition in schizophrenia.

A feature of schizophrenia is disrupted executive function leading to learning difficulties and memory problems. In two experiments we measured the ability of patients with schizophrenia to suppress irrelevant parts of acquired information by intentional (executive) and autonomic (non-executive) strategies. In the first experiment using directed forgetting by lists patients were found to be unable to intentionally suppress recently acquired episodic memories. In a second experiment using a procedure that induces inhibition automatically schizophrenic patients showed levels of inhibition comparable to those of normal controls. These findings indicate that in schizophrenia memory is most impaired in tasks that load heavily on control or executive processes.

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.

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.

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.

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.

Hypnosis Attenuates Executive Cost of Prospective Memory.

Prospective memory is the ability to formulate and carry out actions at the appropriate time or in the appropriate context. This study aimed to identify the effect of hypnosis on prospective memory performance and to analyze the involvement of executive control processes in intention realization in a hypnotically altered state of consciousness. In 1 experiment, manipulating hypnotic instruction in a within-subject fashion, the authors explored the event-based prospective memory performance of 23 volunteers in 3 conditions: baseline, expectation, and execution. The primary result was that executing prospective memory responses, at the same accuracy rate, produced a significantly lower cost of ongoing responses in terms of response latency in the hypnotic state than in wake condition.

Habit learning and the genetics of the dopamine D3 receptor: evidence from patients with schizophrenia and healthy controls.

In this study, the authors investigated the relationship between the Ser9Gly (SG) polymorphism of the dopamine D3 receptor (DRD3) and striatal habit learning in healthy controls and patients with schizophrenia. Participants were given the weather prediction task, during which probabilistic cue-response associations were learned for tarot cards and weather outcomes (rain or sunshine). In both healthy controls and patients with schizophrenia, participants with Ser9Ser (SS) genotype did not learn during the early phase of the task (1-50 trials), whereas participants with SG genotype did so. During the late phase of the task (51-100 trials), both participants with SS and SG genotype exhibited significant learning. Learning rate was normal in patients with schizophrenia. These results suggest that the DRD3 variant containing glycine is associated with more efficient striatal habit learning in healthy controls and patients with schizophrenia.

[Correlation between the effectiveness of atypical antipsychotics and dopamine D3 receptor polymorphism in schizophrenia]. / Az atípusos antipszichotikumok hatékonysága és a dopamin D3-receptor polimorfizmusának kapcsolata schizophreniában.

OBJECT: Numerous relevant variants of dopamine receptors have been identified in schizophrenia. The Ser9Gly gene polymorphism of dopamine D3 receptor is known as a susceptibility factor for the disease. In addition, it has a role in the modification of therapeutic effect of antipsychotics. In this naturalistic study the authors investigated the relationship between this polymorphism and the therapeutic response to atypical antipsychotics. METHOD: 75 patients with schizophrenia according to DSM-IV and 45 healthy controls were recruited. The patients were divided to responder and nonresponder subgroups, cut-off: > 20 point improvement in Global Assessment of Functioning. By polymerase chain reaction the genotype of dopamine D3 receptor of every participant was determined. RESULTS: The Ser9Ser genotype of dopamine D3 receptor was more frequent in the nonresponder subgroup (64%, p = 0.0018). The Ser9 allele was overrepresented among nonresponder patients (82%, p = 0.0172). CONCLUSION: Based on our results, the worse therapeutic response to atypical antipsychotics is associated with Ser9 variant of dopamine D3 receptor.

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.

Effects of a hypnotically altered state of consciousness on intensification of semantic processing.

In a study of the linguistic processes involved in hypnosis, 22 volunteer medical students performed semantic and phonologic fluency tasks and then associative priming tests with 2 delay-lengths in waking alert and hypnotic conditions as well. The participants performed better during semantic than phonological fluency tests in alert and also in hypnotic states, and this difference was significantly greater in hypnosis. The increased semantic performance in hypnosis was accompanied by a decrease of the rule-offending errors. Significant semantic priming effects were detected in both states of consciousness in direct and indirect relations as well as in the automatic, intralexical level, and also when the extralexical control processes were activated. Overall, the results appear to show that the hypnotically altered state of consciousness produces significantly better performance in semantic information processing than can be elicited in alert waking conditions.

Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia.

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.