Anomalies of Imagination, Self-Disorders, and Schizophrenia Spectrum Psychopathology: A Network Analysis

BackgroundAnomalies of imagination encompass disturbances of the basic experiential structure of fantasies and imagery that can be explored in a semi-structured way with the Examination of Anomalous Fantasy and Imagination (EAFI). We aimed (1) to examine the distribution of anomalies of imagination among different diagnostic groups and a group of healthy controls, and (2) to examine their relation with disorders of basic self, perceptual disturbances and canonical state psychopathology of the schizophrenia-spectrum (positive, negative and general symptoms).MethodsThe 81 participants included patients with schizophrenia or other non-affective psychosis (N = 32), schizotypal personality disorder (N = 15) or other mental illness (N = 16) and healthy controls (N = 18). The assessment encompassed EAFI, Examination of Anomalous Self-Experience (EASE), parts of Bonn Scale for the Assessment of Basic Symptoms (BSABS) and Positive and Negative Syndrome Scale (PANSS). For network analysis, the associations of EAFI with the other psychopathological variables were tested by Pearson's correlation coefficient and graphically represented using multidimensional clustering. Comparisons between correlations in the network were tested with Steiger's test.ResultsAnomalies of imagination aggregated significantly in schizophrenia-spectrum disorders compared to other mental illness and healthy controls with no difference between schizophrenia and schizotypal disorder. In the network analysis, anomalies of imagination were closely inter-connected with self-disorders. Although, the anomalies of imagination correlated moderately with perceptual disturbance and positive, negative and general state symptomatology, these dimensions aggregated separately and relatively distant in the network.ConclusionsThe results support that anomalies of imagination are highly characteristic of schizophrenia-spectrum disorders and closely related to self-disorders.

The Role of OXT, OXTR, AVP, and AVPR1a Gene Expression in the Course of Schizophrenia

Schizophrenia is a serious and chronic mental illness, the symptoms of which usually appear for the first time in late adolescence or early adulthood. To date, much research has been conducted on the etiology of schizophrenia; however, it is still not fully understood. Oxytocin and vasopressin as neuromodulators that regulate social and emotional behavior are promising candidates for determining the vulnerability to schizophrenia. The aim of this study was to evaluate the expression of OXT, OXTR, AVP, and AVPR1a genes at the mRNA and protein levels in patients with schizophrenia. Due to the neurodegenerative nature of schizophrenia, the study group was divided into two subgroups, namely, G1 with a diagnosis that was made between 10 and 15 years after the onset of the illness, and G2 with a diagnosis made up to two years after the onset of the illness. Moreover, the relationship between the examined genes and the severity of schizophrenia symptoms, assessed using PANSS (Positive and Negative Syndrome Scale) and CDSS scales (Clinical Depression Scale for Schizophrenia) was evaluated. The analysis of the expression of the studied genes at the mRNA and protein levels showed statistically significant differences in the expression of all the investigated genes. OXT and AVPR1a gene expression at both the mRNA and protein levels were significantly lower in the schizophrenia group, and OXTR and AVP gene expression at both the mRNA and protein levels was higher in the schizophrenia subjects than in the controls. Furthermore, a significant correlation of OXT gene expression at the mRNA and protein levels with the severity of depressive symptoms in schizophrenia as assessed by CDSS was found.

Relationships between Diffusion Tensor Imaging and Resting State Functional Connectivity in Patients with Schizophrenia and Healthy Controls: A Preliminary Study

Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects and acquired resting state fMRI and diffusion tensor imaging. The Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) was used to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal components analysis. Nine of 28 possible region pairs showed consistent (>80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS values correlated with several aspects of the Positive and Negative Syndrome Scale, positively with those involving inwardly directed psychopathology, and negatively with those involving external psychopathology. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.

Belief Updating and Paranoia in Individuals with Schizophrenia

Background and Hypothesis: Persecutory delusions are among the most common delusions in schizophrenia and represent the extreme end of the paranoia continuum. Paranoia is accompanied by significant worry and distress. Identifying cognitive mechanisms underlying paranoia is critical for advancing treatment. We hypothesized that aberrant belief updating, which is related to paranoia in human and animal models, would also contribute to persecutory beliefs in individuals with schizophrenia. Study Design: Belief updating was assessed in 42 schizophrenia and 44 healthy participants, using a 3-option probabilistic reversal learning (3-PRL) task. Hierarchical Gaussian filter (HGF) was used to estimate computational parameters of belief updating. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS). Unusual thought content was measured with the Psychosis Symptom Rating Scale (PSYRATS) and the Peters et al. Delusions Inventory (PDI-21). Worry was measured using the Dunn Worry Questionnaire. Results: Consistent with prior work, paranoia was significantly associated with elevated win-switch rate, prior on volatility and sensitivity to volatility in both schizophrenia and across the whole sample. These relationships were specific to paranoia and did not extend to unusual thought content or measures of anxiety. We did, however, find a significant indirect effect of paranoia on the relationship between prior beliefs about volatility and worry. Conclusions: This work provides evidence that relationships between belief updating parameters and paranoia extend to schizophrenia, may be specific to persecutory beliefs, and contribute to theoretical models implicating worry in the maintenance of persecutory delusions.

Impact of drug-induced Parkinsonism and tardive dyskinesia on health-related quality of life in schizophrenia

Background: Both drug-induced Parkinsonism (DIP) and tardive dyskinesia (TD) have been shown to be associated with lower health-related quality of life (HRQOL) in schizophrenia, but few studies have examined their relative impact. Aims: This study aimed to examine and compare the association of DIP and TD with HRQOL in schizophrenia. Methods: In total, 903 patients with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). EuroQoL five-dimensional (EQ-5D-5L) utility scores were derived from PANSS scores via a previously validated algorithm and used as a measure of HRQOL. Results: In total, 160 (17.7%) participants had only DIP, 119 (13.2%) had only TD, and 123 (13.6%) had both DIP and TD. HRQOL was lowest for participants with both DIP and TD, followed by only DIP group, only TD group, and highest in the group with neither condition. HRQOL scores differed significantly between the four groups, F(3, 892) = 13.724, p < 0.001, [Formula: see text] = 0.044). HRQOL of participants having only DIP or both DIP and TD was significantly lower than those having neither condition. There was no significant interaction between the presence of DIP and TD on the association with HRQOL. Conclusions: DIP was the main antipsychotic-induced movement disorder associated with a poorer HRQOL in patients with schizophrenia. Therefore, clinicians should focus on prevention, detection, and effective management of DIP to optimize HRQOL in patients with schizophrenia.

CHANGES IN SERUM LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR WITH ELECTROCONVULSIVE THERAPY AND PHARMACOTHERAPY AND ITS CLINICAL CORRELATES IN MALE SCHIZOPHRENIA PATIENTS

Objectives: It has been postulated that neurotrophin dysregulation leads to disorganization in neuronal networks, which results in schizophrenia. The current study sets out to evaluate if the finding of lower BDNF levels in schizophrenia patients could be confirmed in an independent cohort, and to investigate if the BDNF levels can be altered with different treatment modalities such as electroconvulsive therapy (ECT) and/or antipsychotic pharmacotherapy (PT). Methods: A total of 54 male patients with schizophrenia and 35 healthy controls were included in the study. Schizophrenia patients were subdivided into two groups as the ones who underwent ECT+PT and only PT. Clinical and sociodemographic data questionnaire, Positive and Negative Syndrome Scale (PANSS) and blood sample collection for BDNF assessment were applied to all patients (on first and last days of admissions) and healthy participants (on the day of the interview). Then, clinical parameters and blood sample outcomes were statistically analyzed. Results: Mean BDNF levels of healthy individuals was significantly higher than mean pre and post-treatment BDNF levels in both PT only and ECT+PT groups. While serum BDNF levels did not increase after ECT+PT, there was a trend level increase in the PT only group. There was no significant correlation between the change in serum BDNF levels with total PANSS scores in either group after treatment. Conclusions: We could confirm previously suggested data of lower serum BDNF levels in schizophrenia patients compared to healthy population but we couldn’t find significant increase in serum BDNF levels with ECT+PT or only PT as some previous studies suggested.

Polymorphisms in MicroRNA Genes Associated with Schizophrenia Susceptibility but Not with Effectiveness of MECT

Schizophrenia (SCZ) is a common and complex psychiatric disease associated with hereditary and environmental risk factors. MicroRNAs (miRNAs or miRs) are small, noncoding RNA molecules that endogenously regulate gene expression. Single nucleotide polymorphisms (SNPs) in related miRNA genes are associated with susceptibility of the disorder. We wonder if the SNPs have influence on the effectiveness of modified electroconvulsive therapy (MECT) for SCZ. rs1625579 within miR-137, rs6577555 within miR-34, and rs2296616 within miR-107 were sequenced in 150 cases and 150 controls to check the potential association between the SNPs and SCZ. Our results showed that allele G in rs1625579 ( p = 0.005 , adjusted OR = 1.379 , 95 % CI = 1.108 − 1.634 ), allele A in rs6577555 ( p = 0.014 , adjusted OR = 1.246 , 95 % CI = 1.045 − 1.463 ), allele G in rs2296616 ( p < 0.001 , adjusted OR = 1.646 , 95 % CI = 1.374 − 1.879 ) are positively associated with the disorder risk. MECT courses did significantly decrease the level of the miRNAs, except for the variant of rs2296616 with the AA genotype. Schizophrenic phenotypes assessed by the positive and negative syndrome scale (PANSS) were improved after MECT, and there was no significant relevance observed between the effectiveness of MECT and the variants of these loci. Thus, our findings indicate that polymorphisms within the loci may be involved in the pathogenesis of SCZ, and MECT is effective and unbiased for patients harboring different genotypes of the loci.

Relationships between Diffusion Tensor Imaging and Resting State Functional Connectivity in Patients with Schizophrenia and Healthy Controls: A Preliminary Study

Schizophrenia is widely seen as a disorder of dysconnectivity. Neuroimaging studies have examined both structural and functional connectivity in the disorder, but these modalities have rarely been integrated directly. We scanned 29 patients with schizophrenia and 25 healthy control subjects and acquired resting state fMRI and diffusion tensor imaging. The Functional and Tractographic Connectivity Analysis Toolbox (FATCAT) was used to estimate functional and structural connectivity of the default mode network. Correlations between modalities were investigated, and multimodal connectivity scores (MCS) were created using principal components analysis. Nine of 28 possible region pairs showed consistent (&gt;80%) tracts across participants. Correlations between modalities were found among those with schizophrenia for the prefrontal cortex, posterior cingulate, and lateral temporal lobes with frontal and parietal regions, consistent with frontotemporoparietal network involvement in the disorder. In patients, MCS values correlated with several aspects of the Positive and Negative Syndrome Scale, positively with those involving inwardly directed psychopathology, and negatively with those involving external psychopathology. In this preliminary sample, we found FATCAT to be a useful toolbox to directly integrate and examine connectivity between imaging modalities. A consideration of conjoint structural and functional connectivity can provide important information about the network mechanisms of schizophrenia.

Surface-Based Spontaneous Oscillation in Schizophrenia: A Resting-State Functional Magnetic Resonance Imaging Study

Schizophrenia (SZ) is considered as a self-disorder with disordered local synchronous activation. Previous studies have reported widespread dyssynchrony of local activation in patients with SZ, which may be one of the crucial physiological mechanisms of SZ. To further verify this assumption, this work used a surface-based two-dimensional regional homogeneity (2dReHo) approach to compare the local neural synchronous spontaneous oscillation between patients with SZ and healthy controls (HC), instead of the volume-based regional homogeneity approach described in previous study. Ninety-seven SZ patients and 126 HC were recruited to this study, and we found the SZ showed abnormal 2dReHo across the cortical surface. Specifically, at the global level, the SZ patients showed significantly reduced global 2dReHo; at the vertex level, the foci with increased 2dReHo in SZ were located in the default mode network (DMN), frontoparietal network (FPN), and limbic network (LN); however, foci with decreased 2dReHo were located in the somatomotor network (SMN), auditory network (AN), and visual network (VN). Additionally, this work found positive correlations between the 2dReHo of bilateral rectus and illness duration, as well as a significant positive correlation between the 2dReHo of right orbital inferior frontal gyrus (OIFG) with the negative scores of the positive and negative syndrome scale in the SZ patients. Therefore, the 2dReHo could provide some effective features contributed to explore the pathophysiology mechanism of SZ.