Executive Functions and Psychopathology Dimensions in Deficit and Non-Deficit Schizophrenia

This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits

Effects of interactions between variation in dopaminergic genes, traumatic life events, and anomalous self-experiences on psychosis proneness : results from a cross-sectional study in a nonclinical sample

Background: there is a growing number of studies showing interactions between genetic polymorphisms associated with dopaminergic neurotransmission and traumatic life events (TLEs) on a risk of psychotic-like experiences (PLEs). Anomalous self-experiences (ASEs) have been associated both with TLEs as well as with PLEs. However, it remains unknown what is the role of ASEs in the complexity of gene - environment interactions on the emergence of PLEs. Patients and methods: we included 445 young adults - university students from three big cities in Poland. We used the Traumatic Events Checklist to assess TLEs, the Inventory of Psychotic-Like anomalous self-experiences in order to measure ASEs, and the Prodromal Questionnaire (PQ16) to record the level of PLEs. The following gene polymorphisms, related to dopaminergic neurotransmission, were determined: the catechol-O-methyltransferase (COMT) rs4680 polymorphism, the dopamine D2 receptor (DRD2) rs6277 polymorphism, and the dopamine transporter 1 (DAT1) rs28363170 polymorphism. Results: there was a significant effect of the interaction between the DAT1 polymorphism, a severity of ASEs, and a history of TLEs on the level of PLEs. Among the DAT1 10R/10R homozygotes with low level of ASEs, a severity of PLEs was significantly higher in individuals with a history of any TLEs. Higher scores of the PQ16 were associated with a greater severity of ASEs both in the DAT1 9R allele carriers and the DAT1 10R/10R homozygotes. Conclusion: our findings imply that genetic liability related to aberrant dopamine transport might impact the association between TLEs and PLEs in subjects with high levels of ASEs

Psychopathology and Integrity of the Superior Longitudinal Fasciculus in Deficit and Nondeficit Schizophrenia

The superior longitudinal fasciculus (SLF) is a white matter bundle that connects the frontal areas with the parietal areas. As part of the visuospatial attentional network, it may be involved in the development of schizophrenia. Deficit syndrome (DS) is characterized by primary and enduring negative symptoms. The present study assessed SLF integrity in DS and nondeficit schizophrenia (NDS) patients and examined possible relationships between it and psychopathology. Twenty-six DS patients, 42 NDS patients, and 36 healthy controls (HC) underwent psychiatric evaluation and diffusion tensor imaging (DTI). After post-processing, fractional anisotropy (FA) values within the SLF were analyzed. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. The PANSS proxy for the deficit syndrome was used to diagnose DS. NDS patients had lower FA values than HC. DS patients had greater negative symptoms than NDS patients. After differentiating clinical groups and HC, we found no significant correlations between DTI measures and psychopathological dimensions. These results suggest that changes in SLF integrity are related to schizophrenia, and frontoparietal dysconnection plays a role in its etiopathogenesis. We confirmed that DS patients have greater negative psychopathology than NDS patients. These results are preliminary; further studies are needed

Effect of Antipsychotic Treatment on Neutrophil-to-Lymphocyte Ratio during Hospitalization for Acute Psychosis in the Course of Schizophrenia—A Cross-Sectional Retrospective Study

Background: Studies have shown that there are deviations in the results of peripheral blood counts, which lead to increased values of the neutrophils-to-lymphocytes ratio (NLR) in schizophrenia. Antipsychotic drugs have proven to lower the levels of pro-inflammatory cytokines and a growing number of studies indicate a similar effect on NLR values. Methods: We identified inpatients with schizophrenia and collected data of NLR at the beginning (NLR1) and end (NLR2) of hospitalization, the status of antipsychotic medication on admission and potential confounding factors. In the statistical analysis, we applied a linear mixed model. Results: After the inclusion and exclusion process the records of 40 patients (np = 40) and 71 hospitalizations (nh = 71) were analyzed. We found that in the group of antipsychotics-naive patients, the NLR1 were significantly higher than the NLR2 values. Such a difference did not occur in the case of non-antipsychotics-naïve patients. Age and the diagnosis of hypothyroidism influenced the value of change in NLR from the beginning to the end of hospitalization in a given patient (ΔNLR). Conclusions: The study confirmed the lowering effect of antipsychotics on NLR values in psychosis. The NLR may potentially be a tool for assessing response to treatment with antipsychotics

The Role of Cytokines in the Pathogenesis of Schizophrenia

Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia

Relationship between White Matter Alterations and Pathophysiological Symptoms in Patients with Ultra-High Risk of Psychosis, First-Episode, and Chronic Schizophrenia

Some symptoms of schizophrenia might be present before full-blown psychosis, so white matter changes must be studied both in individuals with emerging psychosis and chronic schizophrenia. A total of 86 patients—12 ultra-high risk of psychosis (UHR), 20 first episode psychosis (FEP), 54 chronic schizophrenia (CS), and 33 healthy controls (HC)—underwent psychiatric examination and diffusion tensor imaging (DTI) in a 3-Tesla MRI scanner. We assessed fractional anisotropy (FA) and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILS). We found that CS patients had lower FA than FEP patients (p = 0.025) and HC (p = 0.088), and higher MD than HC (p = 0.037) in the right SLF. In the CS group, we found positive correlations of MD in both right ILF (rho = 0.39, p p p r = −0.74, p r = −0.77, p < 0.05). However promising, these findings should be treated as preliminary, and further research must verify whether they can be treated as potential biomarkers of psychosis

The Relationship between Cognitive Functions and Psychopathological Symptoms in First Episode Psychosis and Chronic Schizophrenia

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients

Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis

Peripheral cytokines may affect the brain through chronic activation of microglia and, as a result, can potentially lead to decreased integrity of white matter of cingulum bundle (CB). Therefore, the aim of the study was to analyze the relationships between peripheral inflammatory markers and the integrity of the CB in various states: from healthy controls, through prodromal states and first-episode psychosis, to long-term schizophrenia. The integrity of the CB was measured using diffusion tensor imaging. We analyzed six parameters: CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. We found that levels of IL-6 and IFN-γ differed significantly between groups. Initial analysis showed some correlations between the inflammatory markers and CB integrity, in particular a correlation with IL-6 that was present in several groups. However, none of the analyzed parameters were associated with the integrity of the CB after correction for multiple comparisons. Conclusions: Our results supported our hypothesis that there are increased levels of inflammatory markers in psychotic disorders, but did not allow to confirm our hypothesis that there is a link between increased peripheral inflammatory markers and decreased integrity of the CB. However, we found some interesting trend levels that need to be verified in larger studies

Relationship of Corpus Callosum Integrity with Working Memory, Planning, and Speed of Processing in Patients with First-Episode and Chronic Schizophrenia

There is a paucity of reports examining the relationship between the integrity of the corpus callosum (CC) and different aspects of cognitive functioning in patients with first-episode (FES) and chronic schizophrenia (CS) simultaneously; furthermore, what results exist are inconclusive. We used diffusion tensor imaging tractography to investigate differences in integrity in five regions of the CC between FES, CS, and healthy controls (HC). Additionally, we analyzed correlations between these regions’ integrity and working memory, planning, and speed of processing. Eighteen patients with FES, 55 patients with CS, and 30 HC took part in the study. We assessed cognitive functions with four tasks from Measurement and Treatment Research to Improve Cognition in Schizophrenia. Patients with CS showed lower fractional anisotropy (FA) in Region 5 (statistical trend) and higher mean diffusivity (MD) in Regions 4 and 5 than HC, and patients with FES had higher MD in Region 3 (statistical trend) than HC. Both clinical groups performed worse on working memory and speed of processing tasks than HC, and patients with CS scored worse than HC on independent planning, and worse than FES and HC on dependent planning. Moreover, in patients with CS, MD in Region 3 was correlated with verbal working memory. Our results suggest that patients with FES and CS are characterized by impaired integrity of the middle and posterior CC, respectively. We confirmed that both clinical groups have cognitive impairments. Moreover, the integrity of the middle CC may influence planning in patients with CS

Coping styles and symptomatic manifestation of first-episode psychosis: Focus on cognitive performance

Cognitive deficits are widely observed in patients with psychosis and represent one of most important determinants of functional outcomes. It has been shown that patients with psychosis prefer maladaptive coping strategies over active coping styles. However, it remains unknown whether cognitive impairments are related to coping styles in psychotic disorders. Therefore, the aim of this study was to assess whether cognitive deficits observed in patients with first-episode psychosis (FEP) might impact the use of specific coping strategies. We recruited 40 FEP patients and 35 healthy controls. In our study, FEP patients were more likely to use maladaptive coping styles after adjustment for education level and medication effects. The use of maladaptive coping strategies was associated with greater impairments of visuospatial/constructional abilities and language skills in FEP patients. In addition, lower odds of using adaptive coping were related to higher levels of depressive symptoms in the group of patients. Adaptive coping was associated with better global cognitive performance in healthy controls. Our results indicate that cognitive impairments, especially worse performance of visuospatial/constructional abilities and language skills, might be related to the preference of maladaptive coping strategies. Lower odds of using adaptive coping styles might be associated with more severe depressive symptomatology.This study was funded from science budget resources granted for the years 2016-2019 (the Iuventus Plus grant awarded by the Ministry of Science and Higher Education, grant number: IP2015 052474).Scopu