EEG alpha reactivity on eyes opening discriminates patients with schizophrenia and schizoaffective disorder.

OBJECTIVE: Alpha activity in the electroencephalogram (EEG) is typically dominant during rest with closed eyes but suppressed by visual stimulation. Previous research has shown that alpha-blockade is less pronounced in schizophrenia patients compared to healthy individuals, but no studies have examined it in schizoaffective disorder. METHODS: A resting state EEG was used for the analysis of the alpha-reactivity between the eyes closed and the eyes opened conditions in overall (8 - 13 Hz), low (8 - 10 Hz) and high (10 - 13 Hz) alpha bands in three groups: schizophrenia patients (SC, n = 30), schizoaffective disorder (SA, n = 30), and healthy controls (HC, n = 36). All patients had their first psychotic episode and were receiving antipsychotic therapy. RESULTS: A significant decrease in alpha power was noted across all subjects from the eyes-closed to eyes-open condition, spanning all regions. Alpha reactivity over the posterior regions was lower in SC compared to HC within overall and high alpha. SA showed a trend towards reduced alpha reactivity compared to HC, especially evident over the left posterior region within the overall alpha. Alpha reactivity was more pronounced over the middle and right posterior regions of SA as compared to SC, particularly in the high alpha. Alpha reactivity in SC and SA patients was associated with various negative symptoms. CONCLUSIONS: Our findings imply distinct alterations in arousal mechanisms in SC and SA and their relation to negative symptomatology. Arousal is more preserved in SA. SIGNIFICANCE: This study is the first to compare the EEG features of arousal in SC and SA.

The ANKK1/DRD2 gene TaqIA polymorphism (rs1800497) is associated with the severity of extrapyramidal side effects of haloperidol treatment in CYP2D6 extensive metabolizers with schizophrenia spectrum disorders.

OBJECTIVES: Extrapyramidal symptoms (EPS) are one of the most prominent side effects of haloperidol. Variability of EPS severity may be associated with the genetic factors, affecting both haloperidol pharmacokinetics (e.g., CYP2D6) and pharmacodynamics (e.g., DRD2, ANKK1). We conducted a 3-week prospective study to investigate the associations of ANKK1/DRD2 TaqIA (rs1800497), DRD2 -141C Ins/Del (rs1799732) polymorphisms and CYP2D6 metabolic phenotype on the efficacy of haloperidol treatment and severity of EPS in patients with schizophrenia spectrum disorders. METHODS: In total, 57 inpatients with schizophrenia spectrum disorders (24 (42.1%)) females; age -46.7 (11.8) years (M(SD)) of European ancestry were enrolled. BARS and SAS scales were used to assess EPS. PANSS and CGI scales - to assess the efficacy of haloperidol treatment. Genotyping was performed by real-time PCR. CYP2D6 metabolic phenotype was predicted by the CYP2D6 *3, *4, *5, *6, *9, *10, *41 and xN genotypes. RESULTS: Minor C allele of TaqIA was associated with higher scores of BARS (p=0.029) and SAS (p=0.024) on day 21 and minor Del allele of -141C Ins/Del - with more prominent clinical improvement by CGI scale (p=0.007) but not by PANSS. These differences were observed only in extensive CYP2D6 metabolizers, although no associations with the metabolic type itself were found. General linear model showed that the combination of TaqIA genotype and metabolic type was significantly associated with BARS score on day 21 (p=0.013). CONCLUSIONS: Our results highlight the importance of using both pharmacokinetic and pharmacodynamic genetic markers for predicting haloperidol treatment response to personalize schizophrenia spectrum disorders treatment.

Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review.

OBJECTIVE: The objective of this study was to provide comprehensive evidence synthesis including all available up-to-date data about the prevalence of N-methyl D-aspartate receptor (NMDAR) antibodies (ABs) in psychotic patients in order to evaluate the clinical relevance of ABs as well as to specify potential explanations of the heterogeneity of the findings and determine areas for further research. METHODS: A literature search was conducted using the PubMed/Medline, Web of Knowledge, and Scopus databases. RESULTS: Forty-seven studies and 4 systematic reviews (including 2 meta-analyses) were included in the present review. Studies that used cell-based assays (CBAs) provided heterogeneous results on AB prevalence, obviously depending on the type of detection assay and sample characteristics. Improvement of AB detection methods is necessary to determine the real prevalence of ABs across different groups of patients and healthy people. Live CBAs seem to have better sensitivity but probably poorer specificity than fixed CBAs. Moreover, some links between AB-positive status and acute symptoms are possible. A small amount of data on immunotherapy in AB-positive patients raises the possibility of its effectiveness but obviously require further research. CONCLUSIONS: NMDAR ABs are definitely present in a subset of psychotic patients. NMDAR ABs might shape psychosis and underlie some symptoms, and immunotherapy might be regarded as a treatment option for patients failing to respond to other therapies.

Eye Movements and Cognitive Functioning in Patients With Schizophrenia Spectrum Disorders: Network Analysis.

Background: Eye movement parameters are often used during cognitive functioning assessments of patients with psychotic spectrum disorders. It is interesting to compare these oculomotor parameters with cognitive functions, as assessed using psychometric cognitive tests. A network analysis is preferable for understanding complex systems; therefore, the aim of this study was to determine the multidimensional relationships that exist between oculomotor reactions and neurocognition in patients with schizophrenia spectrum disorders. Materials and Methods: A total of 134 subjects (93 inpatients with schizophrenia spectrum disorders (ICD-10) and 41 healthy volunteers) participated in this study. Psychiatric symptom severity was assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Young Mania Rating Scale. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale, and akathisia was assessed using the Barnes Akathisia Rating Scale. Eye movements were recorded using an eye-tracker SMI RED 500, and cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. The statistical analyses were conducted using Minitab 17 Statistical Software, version 17.2.1. Data visualization and additional analyses were performed in the R 4.0.3 environment, using RStudio V 1.3.1093 software. Results: A network model of neurocognitive and oculomotor functions was constructed for the patients. In the full network (which includes all correlations) the median antisaccade latency value is the central element of the oculomotor domain, and the Symbol Coding test, the Digit Sequencing test, and the Verbal Fluency test are central elements in the neurocognitive domain. Additionally, there were connections between other cognitive and oculomotor functions, except for the antisaccade error latency in the oculomotor domain and the Token Motor Task in the neurocognitive domain. Conclusion: Network analysis provides measurable criteria for the assessment of neurophysiological and neurocognitive abnormalities in patients with schizophrenic spectrum disorders and allows to select key targets for their management and cognitive remediation.

Network analysis of cognitive deficit in patients with schizophrenia spectrum disorders.

BACKGROUND: Cognitive impairments are found in 80% of patients with schizophrenia. The severity of these impairments significantly affects the recovery of patients in terms of social functioning.Network analysis is the most suitable approach for studying complex relationships among cognitive functions. AIM: To build a network model of neurocognitive functions for identifying both the severity of impairments in individual functions and the vertices central to the whole model. METHODS: The study included 115 patients with schizophrenia and schizophrenia spectrum disorders and a comparison group, comprising 99 healthy subjects. The severity of clinical symptoms was assessed using the PANSS, CDSS and YMRS, and the SAS and BARS for extrapyramidal symptoms and akathisia. Subjects from the comparison group completed screening questionnaires QIDS-SR and PQ-16. Neurocognitive functions were assessed using the BACS. RESULTS: The patients performed worse than the healthy subjects on all tests. In the cognitive network models of healthy subjects, fewer connections were revealed and the central place was occupied by working memory, the functioning of which depends upon everyday functioning in the community. In the cognitive models of patients there was a greater connectedness of neurocognitive functions. Furthermore, the central place of the networks in patients is occupied by the processing speed, evaluated primarily using the Symbol Coding test, which reflects the dependence of patient activity on lower-order functions. CONCLUSION: The processing speed deficit is key to schizophrenia and it may be considered a potential endophenotype of the disease.

EEG correlates of face recognition in patients with schizophrenia spectrum disorders: A systematic review.

OBJECTIVE: To systematically assess EEG studies and evaluate neuropsychological changes of face recognition in the context of neutral face stimuli in individuals with schizophrenia spectrum disorders. METHODS: A literature search was conducted using the PubMed database from inception to March 2018. Studies included in the review measured any event-related potentials, neural oscillations, or phase synchrony. RESULTS: A total of 113 articles were identified. Twenty-nine studies were included for the review. The majority of the studies focused on the N170 component. Smaller N170 amplitudes were consistently reported in schizophrenia patients compared to the healthy control group. Significant correlations between N170 amplitudes and social functioning scales were reported. Other results were quite inconsistent; however, group differences were more prominent for tasks with specific conditions. CONCLUSIONS: Older patients with longer disease duration show more consistent neuropsychological correlations. Alterations of event-related potentials are likely to be linked to higher severity of symptoms. The N170 component seems to be the most promising event-related potential to be used for evaluation of present status and for dynamic control of cognitive impairments, social functioning, and rehabilitation effectiveness. SIGNIFICANCE: This systematic review provides evidence of (1) neuropsychological alterations of face processing outside an emotional context, and (2) a potential role of N170 as a diagnostic and treatment monitoring biomarker.

EEG coherence in a mental arithmetic task performance in first episode schizophrenia and schizoaffective disorder.

OBJECTIVES: To evaluate the coherence values of the cortical bands in patients with first episode schizophrenia and schizoaffective disorder during the performance of a mental arithmetic task. METHOD: We analysed EEG coherence in the resting state and subsequently while counting down from 200 in steps of 7 in 32 first episode schizophrenia patients (SZ), 32 patients with first episode schizoaffective disorder (SA) and 40 healthy controls (HC). RESULTS: Task performance in HC is characterised by decreased coherence in the alpha bands and increased coherence in the beta 2 and gamma bands in frontal sites. In SZ, coherence decreases in the alpha band, whereas in SA it substantially increases in the alpha, beta1, beta 2 and gamma bands. CONCLUSIONS: Despite no differences in performance on a behavioural level, SA patients demonstrate a paradoxical increase in both low and fast frequency bands during the performance of a mental arithmetic task, while, patients with SZ show a decreased coherence in the alpha band, presumably alluding to the excessive excitatory (in SA) and inhibitory (in SZ) mechanisms in cognitive processing. SIGNIFICANCE: The current study provides evidence for the distinction of neurophysiological mechanisms of cognitive processing between SZ and SA.

The Dopamine Receptor D2 C957T Polymorphism Modulates Early Components of Event-Related Potentials in Visual Word Recognition Task.

BACKGROUND: Visual word recognition is one of the central topics in cognitive psychology and cognitive neuroscience. Genetic factors are known to contribute to the visual word recognition, but no genes associated with this process have been identified so far. We studied the impact of the DRD2 C957T polymorphism on the efficiency of visual word recognition by measuring its neuronal correlates and behavioral parameters. Early (~200 ms) components of event-related potentials (ERP) were recorded during a lexical decision task. The DRD2 C957T polymorphism is thought to be associated with D2 receptor's availability and binding potential. Earlier studies have demonstrated the influence of this variation on perception and processing of verbal stimuli. The DRD2 C957T is also associated with schizophrenia, with the C allele being the risk allele. METHODS: Electroencephalogram, genetic, and behavioral data were collected from 96 healthy individuals (53.1% men). ERPs were recorded for words and pseudowords in implicit and explicit tasks. Two regions of interests in the left ventral temporal cortex, whose role in early visual word processing is well established, were selected for analysis. RESULTS: The results showed the main effect of the DRD2 C957T polymorphism on P200 amplitude. Carriers of the TT genotype had higher P200 amplitudes compared to subjects with schizophrenia risk C allele. Within-group comparisons demonstrated a better ability to adjust attention to orthographic stimuli depending on task demands and lexicality in the TT group. CONCLUSION: The results of the study suggest that the DRD2 C957T polymorphism modulates early stages of visual word recognition.

Cognitive bias salience in patients with schizophrenia in relation to social functioning: A four-case observation study.

Neurocognition and social cognition are the core deficits influencing social outcomes in patients with schizophrenia. These deficits are present in the prodromal phase, throughout the illness and in first-degree relatives. They are considered in the framework of neurodevelopmental or neurodegenerative models as well as candidates for endophenotypes of schizophrenia. Four clinical cases with patients reflecting different cognitive profiles were chosen to demonstrate heterogeneity of cognitive biases and their influence on social function in vivo. The patients had undergone a number of neurocognitive and social cognitive measures. Better functioning was observed in patients with less affected domains of emotional processing and theory of mind, while neurocognitive statuses were incongruent to levels of social functioning. Further investigation on large samples concerning capacity for empathy and its role in social functioning is needed.

Oxytocin and Social Cognitions in Schizophrenia: A Systematic Review.

Schizophrenia is a chronic multifactorial disorder. Over the last years, there has been a growing interest in cognitive deficits in schizophrenia, which is considered by many as the core abnormality of the disease. In the systematic review we focus on the social cognition and its correlation with the neuropeptide oxytocin, which is shown to be involved in the emotion recognizing processes, in the trust behavior and many other aspects of social functioning. The systematic review was performed in order to summarize the data on the liaison of oxytocin with the social cognition impairment in schizophrenia patients. Oxytocin is assumed to be a potential therapeutic agent for schizophrenia, with a special link to social cognitive functions. The oxytocinergic system is a promising neuromodulator of emotion recognition that may have the potential to normalize the social dysfunction seen in schizophrenia. Further studies are required to provide more data on the correlations between oxytocin and socialcognition as well as other schizophrenia symptoms.

EEG correlates of a mental arithmetic task in patients with first episode schizophrenia and schizoaffective disorder.

OBJECTIVE: To evaluate the spectral power of the cortical bands in patients with first episode schizophrenia and schizoaffective disorder at rest and during the performance of a mental arithmetic task. METHODS: We analyzed EEG spectral power (SP) in the resting state and subsequently while counting down from 200 in steps of 7, in 32 first episode schizophrenia patients (SZ), 32 patients with first episode schizoaffective disorder (SA) and healthy controls (HC, n=40). Behavioral parameters such as accuracy and counting speed were also evaluated. RESULTS: Both SZ and SA patients were slower in counting than HC, no difference was obtained in the accuracy and counting speed in the patient groups. In the resting state patients showed elevated midline theta power, off-midline anterior beta 2 power and decreased central/posterior alpha power. The SA group occupied an intermediate position between the schizophrenia patients and controls. In task performance patients lacked a typical increase of midline theta, left anterior beta 2, and anterior gamma power; however, schizoaffective patients demonstrated a growing trend of power in the gamma band in left anterior off-midline sites similar to HC. Moreover, alpha power was less inhibited in schizoaffective patients and more pronounced in schizophrenia patients indicating distinct inhibitory mechanisms in these psychotic disorders. CONCLUSIONS: Patients with SA demonstrate less alteration in the spectral power of bands at rest than SZ, and present spectral power changes during cognitive task performance close to the controls. SIGNIFICANCE: Our study contributes to the present evidence on the neurophysiological distinction between schizophrenia and schizoaffective disorder.

Aspects of metabolic changes in first-episode drug-naïve schizophrenic patients.

UNLABELLED: Aim The aim of the study was to investigate the state of parameters characterising different sites of metabolism and the degree of endogenous intoxication in first-episode drug-naïve schizophrenic [first episode of schizophrenia (FES)] patients. It is hypothesised that the FES is the initial step in the development of pathologically disturbed biochemical status that is characteristic of chronic schizophrenia. METHODS: Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, serum concentrations of middle-mass endotoxic molecules (MMEM) and malondialdehyde and parameters of the serum albumin functional state were measured in 26 FES patients and 15 age-matched healthy controls. RESULTS: Severity of disorder before the treatment was 75.5 ± 2.2, according to Positive and Negative Syndrome Scale score. FES patients were characterised by significant increase in MAO activity (99%) and MMEM concentration (124%) and significant decrease in SSAO activity (26%) as compared with controls. Changes of all other parameters were insignificant. Regression analysis has showed a significant relationship of three parameters - MAO, SSAO and MMEM, with values of PANNS score. Two methods of extraction of factor analysis revealed that MAO and SSAO belonged to Factor 1, whereas MMEM and albumin functional parameters belonged to Factor 2. CONCLUSION: Comparing our earlier data on chronic schizophrenic patients with present data, we hypothesise that FES patients are at the stage that leads to a stable, pathological state of metabolism.

Effectiveness of the integrated long-term program of management of patients after first psychotic episode in 5-year follow-up.

The Early Intervention Centre (First episode clinic, FEC) that provides specific service programs to this particular target group of patients with early psychosis opened in November 2000 as a day clinic at the Moscow Research Institute of Psychiatry. To date, FEC programs consistent with the developed model have been established in 30 regions across Russia. 5-year follow-up data are available for 114 patients who received such care in the FEC. In more than 30% of cases complete remission was maintained over the 5 years. The number of relapses increased on the 2nd and 3rd years, but later decreased more than by one half. The relapses were mostly treated in day clinic or outpatient settings and did not require hospital admissions. More than 73% of the patients maintained their social achievements with no losses. By the end of the 5th year only 1/5 of the cases were formally recognized as unemployable due to psychiatric disability. Significantly better clinical and psychosocial outcomes have been shown in comparison with a control group of patients, treated in routine psychiatric services.