Cognitive Impairment In Schizophrenia Research Articles

Eosinophils and Cognitive Impairment in Schizophrenia: A New Perspective.

Schizophrenia is a complex psychiatric disorder characterized by a wide array of cognitive impairments. While research has predominantly focused on the neurological aspects of schizophrenia, emerging evidence suggests that the immune system, specifically eosinophils, may play a significant role in the cognitive deficits associated with the disorder. This review presents a novel perspective on the interplay between eosinophils and cognitive impairment in schizophrenia. Eosinophils, traditionally associated with allergic responses and inflammation, have garnered limited attention within the realm of neuropsychiatry. Recent studies have hinted at a potential link between eosinophil activation and the pathogenesis of schizophrenia. In this comprehensive review, we delve into the world of eosinophils, elucidating their nature, functions, and interactions with the immune system. We examine the cognitive deficits observed in individuals with schizophrenia and discuss existing theories on the etiology of these impairments, focusing on immune system involvement. The paper also highlights the evolving body of research that supports the idea of eosinophilic influence on schizophrenia-related cognitive deficits. Furthermore, we explore potential mechanisms through which eosinophils may exert their effects on cognitive function in schizophrenia, including interactions with other immune cells and inflammatory pathways. By discussing the clinical implications and potential therapeutic avenues stemming from this newfound perspective, we underscore the practical significance of this emerging field of research. While this paper acknowledges the limitations and challenges inherent in studying eosinophils within the context of schizophrenia, it serves as a posit for novel thought in this vexing disease space as well as a call to action for future research endeavors. By providing a comprehensive survey of the existing literature and posing unanswered questions, we aim to inspire a reimagining of the relationship between eosinophils and cognitive impairment in schizophrenia, ultimately advancing our understanding and treatment of this debilitating disorder.

Cross-cohort replicable resting-state functional connectivity in predicting symptoms and cognition of schizophrenia.

Schizophrenia (SZ) is a debilitating mental illness characterized by adolescence or early adulthood onset of psychosis, positive and negative symptoms, as well as cognitive impairments. Despite a plethora of studies leveraging functional connectivity (FC) from functional magnetic resonance imaging (fMRI) to predict symptoms and cognitive impairments of SZ, the findings have exhibited great heterogeneity. We aimed to identify congruous and replicable connectivity patterns capable of predicting positive and negative symptoms as well as cognitive impairments in SZ. Predictable functional connections (FCs) were identified by employing an individualized prediction model, whose replicability was further evaluated across three independent cohorts (BSNIP, SZ = 174; COBRE, SZ = 100; FBIRN, SZ = 161). Across cohorts, we observed that altered FCs in frontal-temporal-cingulate-thalamic network were replicable in prediction of positive symptoms, while sensorimotor network was predictive of negative symptoms. Temporal-parahippocampal network was consistently identified to be associated with reduced cognitive function. These replicable 23 FCs effectively distinguished SZ from healthy controls (HC) across three cohorts (82.7%, 90.2%, and 86.1%). Furthermore, models built using these replicable FCs showed comparable accuracies to those built using the whole-brain features in predicting symptoms/cognition of SZ across the three cohorts (r = .17-.33, p < .05). Overall, our findings provide new insights into the neural underpinnings of SZ symptoms/cognition and offer potential targets for further research and possible clinical interventions.

The Bidirectional Relationship between Weight Gain and Cognitive Function in First-Episode Schizophrenia: A Longitudinal Study in China.

Patients with schizophrenia often encounter notable weight gain during their illness, heightening the risk of metabolic diseases. While previous studies have noted a correlation between obesity and cognitive impairment in schizophrenia, many were cross-sectional, posing challenges in establishing a causal relationship between weight gain and cognitive function. The aim of this longitudinal study is to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) during the initial 6-month antipsychotic treatments. Employing linear and logistic regression analyses, the study involved 337 participants. Significantly, baseline scores in processing speed (OR = 0.834, p = 0.007), working memory and attention (OR = 0.889, p = 0.043), and executive function (OR = 0.862, p = 0.006) were associated with clinically relevant weight gain (CRW, defined as an increase in body weight > 7%) at the 6-month endpoint. On the other hand, CRW correlated with improvements in the Brief Visuospatial Memory Test (p = 0.037). These findings suggest that patients with lower baseline cognitive performance undergo more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cognitive function in first-episode schizophrenia patients.

Schizophrenia and Nicotine - A Bittersweet Psychiatric Story

Abstract Background: Schizophrenia is a chronic mental disorder affecting mood, perception, and most importantly cognition. This severely interferes with the functioning of such patients. On the other hand, nicotine use (both smoke and smokeless tobacco) is very much prevalent in schizophrenic patients, much more than normal population. This study aims to find the relation between nicotine use and cognition in schizophrenic patients. Methodology: Fifty-six new patients diagnosed with schizophrenia of both sexes between ages 18 and 60 years, giving valid and informed consent, were selected for the study. Fagerstrom test for nicotine dependence was done and the patients were divided into two groups: scores 4 or less (low-to-moderate dependence) and scores 5 or more (severe dependence). The Cognitive Assessment Interview was performed. Then, an independent sample t-test was used to compare the scores on various cognitive domains between the two groups. Results: The cognitive scores were better in the group with severe tobacco dependence, both globally and across individual domains. These associations were statistically significant (P = 0.001). The mean difference was highest in the social cognition group. Among all the domains, the t-value was highest for the speed of processing domain, indicating that this particular cognitive domain has the best discriminative value when compared between two groups of nicotine users. Conclusions: Hence, to conclude, whether nicotine has indeed a beneficial effect on cognition in schizophrenia has to be investigated longitudinally so that a possible treatment option to address cognitive impairment in schizophrenia is obtained. Extensive longitudinal studies needs to be conducted to better understand the long-term effect of tobacco use and cognition in schizophrenia patients.

Brain network analysis of working memory in schizophrenia based on multi graph attention network

The cognitive impairment in schizophrenia (SZ) is characterized by significant deficits in working memory task. In order to explore the brain changes of SZ during a working memory task, we performed time-domain and time–frequency analysis of event related potentials (ERP) of SZ during a 0-back task. The P3 wave amplitude was found to be significantly lower in SZ patients than in healthy controls (HC) (p < 0.05). The power in the θ and α bands was significantly enhanced in the SZ group 200 ms after stimulation, while the θ band was significantly enhanced and the β band was weakened in the HC group. Furthermore, phase lag index (PLI) based brain functional connectivity maps showed differences in the connections between parietal and frontotemporal lobes between SZ and HC (p < 0.05). Due to the natural similarity between brain networks and graph data, and the fact that graph attention network can aggregate the features of adjacent nodes, it has more advantages in learning the features of brain regions. We propose a multi graph attention network model combined with adaptive initial residual (AIR) for SZ classification, which achieves an accuracy of 90.90 % and 78.57 % on an open dataset (Zenodo) and our 0-back dataset, respectively. Overall, the proposed methodology offers promising potential for understanding the brain functional connections of schizophrenia.

Neuroimaging features of cognitive impairments in schizophrenia and major depressive disorder.

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

The cognitive improvement in patients with schizophrenia following low-intensity repetitive transcranial magnetic stimulation could last for 6 months: A randomized controlled trial

Cognitive impairments are a core symptom of schizophrenia. Although low-intensity repetitive transcranial magnetic stimulation (rTMS) also has cognitive improving effect like the commonly used high-intensity rTMS, it has not been applied in schizophrenia yet. To fill this gap, inpatients with schizophrenia were randomized to receive 20 sessions of daily adjunctive active low-intensity rTMS in 4 weeks, or sham treatment. At baseline, 4 weeks, and 6 months, the Positive and Negative Syndrome Scale (PANSS) was used to assess psychotic symptom severity, while the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color and Word Test (SCWT) were used to assess cognitive functions. Compared to the sixty-nine patients receiving sham treatment, those fifty-nine patients receiving active rTMS performed better in all cognitive domains at post-treatment with small to large effect sizes. This superiority of active rTMS over sham treatment remained significant at 6-month follow-up, with small to large effect sizes, except for visuospatial function and delayed memory. The reduction in PANSS scores were not correlated with cognitive improvements. Our findings provide evidence for using low-intensity rTMS to ameliorate cognitive impairments in schizophrenia. More research are needed to determine the optimal intensity for each domain of cognitive functions.

D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia

The hypothesis of N-methyl-D-aspartate receptor (NMDAR) dysfunction for cognitive impairment in schizophrenia constitutes the theoretical basis for the translational application of NMDAR co-agonist D-serine or its analogs. However, the cellular mechanism underlying the therapeutic effect of D-serine remains unclear. In this study, we utilize a mouse neurodevelopmental model for schizophrenia that mimics prenatal pathogenesis and exhibits hypoexcitability of parvalbumin-positive (PV) neurons, as well as PV-preferential NMDAR dysfunction. We find that D-serine restores excitation/inhibition balance by reconstituting both synaptic and intrinsic inhibitory control of cingulate pyramidal neurons through facilitating PV excitability and activating small-conductance Ca2+-activated K+ (SK) channels in pyramidal neurons, respectively. Either amplifying inhibitory drive via directly strengthening PV neuron activity or inhibiting pyramidal excitability via activating SK channels is sufficient to improve cognitive function in this model. These findings unveil a dual mechanism for how D-serine improves cognitive function in this model.

Structural abnormalities in the Fronto-Parietal Network: Linking white matter integrity to sustained attention deficits in Schizophrenia

Schizophrenia is associated with a range of cognitive deficits, among which impairments in sustained attention are particularly significant. Previous research has investigated functional changes in the fronto-parietal network (FPN) related to attentional control in schizophrenia. However, the role of structural connectivity within the FPN in sustained attention deficits remains under-explored. Utilizing diffusion tensor imaging (DTI), this study investigated white matter integrity in 75 participants, comprising 37 individuals with schizophrenia (SZ) and 38 healthy controls (HC). Psychomotor vigilance task (PVT) performance was assessed to gauge sustained attention. The SZ group showed a significant reduction in fractional anisotropy (FA) and streamline counts within white matter tracts connecting frontal and parietal regions, compared to the HC group. Further, significant negative correlations were found between PVT performance and white matter integrity measures within the SZ group, specifically in the left FPN. Our findings indicate that structural abnormalities in the FPN are associated with sustained attention deficits in schizophrenia. These results contribute to our understanding of the neurobiological mechanisms underlying cognitive impairments in schizophrenia and offer potential avenues for targeted therapeutic interventions. Further research is warranted to validate these outcomes and explore their clinical implications.

Relationship Between Sleep Disturbances and Cognitive Impairment of Schizophrenia

Schizophrenia, cognitive impairments, and sleep disturbances and their effects on each other have been the topics of heavy research in recent years. With the realization of their impacts on each other, More and more studies have been set up to try to find the relationships between the three. The purpose of this article is to go through a few of these studies and clinical cases that focused upon or show traces of evidence of the relationship between sleep, cognitive impairment, and schizophrenia to look for and discuss the correlation and possible causational relationships between sleep disturbance and cognitive impairment in schizophrenia. In total, five studies and one clinical case series will be reviewed in this article to look for the relationship between sleep and schizophrenia. In addition, a discussion focused on the possible explanation of the relationship between sleep and cognitive functions in schizophrenia that are based on this research will be presented to explain the correlation between sleep and cognitive functions of schizophrenic patients.

Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex.

Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program's Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

Structural-functional connectivity deficits of callosal-white matter-cortical circuits in schizophrenia

Schizophrenia is increasingly recognized as a disorder with altered integration between large-scale functional networks and cortical-subcortical pathways. This spatial long-distance information communication must be associated with white matter (WM) fiber bundles. With accumulating evidence that WM functional signals reflect the intrinsic neural activities, how the deep callosal organization modulates cortical functional activities through WM remains unclear in schizophrenia. Using a data-driven method, we identified nine WM and gray matter (GM) functional networks, and then parcellated corpus callosum into distinct sub-regions. Combining functional connectivity and fiber tracking analysis, we estimated the structural and functional connectivity changes of callosal-WM-cortical circuits in schizophrenia. We observed higher structural and functional connectivity between corpus callosum, WM and GM functional networks involving visual network (visual processing), executive control network (executive controls), ventral attention network (processing of salience), and limbic network (emotion processing) in schizophrenia compared to healthy controls. We also found nine abnormal pathways of callosal-WM-cortical circuits involving the above networks and default mode network (self-related thought). These results highlight the role of connectivity deficits in callosal-WM-cortical circuits may play in understanding the delusions, hallucinations and cognitive impairment of schizophrenia.

Gender difference in association between clinical symptoms and alexithymia in chronic schizophrenia: A large sample study based on Chinese Han population

BackgroundAlexithymia, a prevalent social cognitive impairment in schizophrenia, remains insufficiently studied. Though some studies propose a link between alexithymia and clinical symptoms of schizophrenia, this connection lacks consistent confirmation. Additionally, there is limited research on gender difference in alexithymia among schizophrenia patients. To fill this gap, our study aimed to conduct a large-sample survey of Chinese Han patients with chronic schizophrenia to explore whether there are gender differences between clinical symptoms and alexithymia. MethodsWe obtained sociodemographic characteristics of 987 schizophrenia patients, measured their clinical symptoms using the Positive and Negative Syndrome Scale (PANSS), and assessed their self-reported alexithymia using the Toronto Alexithymia Scale (TAS-20). ResultsIn patients with chronic schizophrenia, the prevalence of alexithymia did not differ between genders (male: 35.51 % vs. female: 26.91 %, P = 0.018). Correlation and linear regression analyses revealed that PANSS scores and TAS-20 scores were widely correlated in both male and female patients. In particular, multiple linear regression analysis showed that the TAS total score was positively correlated with negative symptoms and cognitive symptoms in male patients, while it was positively correlated with negative symptoms and depressive symptoms in female patients. ConclusionOur study suggests that the prevalence of alexithymia in patients with chronic schizophrenia does not differ between genders. Negative symptoms are related to the TAS-20 total score in both male and female patients, while cognitive symptoms are only related to the TAS-20 total score in male patients, and depressive symptoms are only related to the TAS-20 total score in female patients.

Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review.

Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well-being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. Fifty-eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

Effect of anticholinergic burden on brain activity during Working Memory and real-world functioning in patients with schizophrenia.

Cognitive impairment has been associated with poor real-world functioning in patients with Schizophrenia. Previous studies have shown that pharmacological treatment with anticholinergic properties may contribute to cognitive impairment in Schizophrenia. We investigated the effect of the anticholinergic burden (ACB) on brain activity, cognition, and real-world functioning in Schizophrenia. We hypothesized that greater ACB would be associated with altered brain activity along with poorer cognitive performance and lower real-world functioning. A sample of 100 patients with a diagnosis of schizophrenia or schizoaffective disorder was recruited in the naturalistic multicenter study of the Italian Network for Research on Psychoses (NIRP) across 7 centres. For each participant, ACB was evaluated using the Anticholinergic Cognitive Burden scale. The association of ACB with brain function was assessed using BOLD fMRI during the N-Back Working Memory (WM) task in a nested cohort (N=31). Real-world functioning was assessed using the Specific Level of Functioning (SLOF) scale. Patients with high ACB scores (≥3) showed lower brain activity in the WM frontoparietal network (TFCE corrected alpha <0.05) and poorer cognitive performance (p=0.05) than patients with low ACB scores (<3). Both effects were unaffected by demographic characteristics, clinical severity, and antipsychotic dosage. Moreover, patients with high ACB showed poorer real-world functioning than patients with lower ACB (p=0.03). Our results suggest that ACB in Schizophrenia is associated with impaired WM and abnormal underlying brain function along with reduced real-world functioning. Clinical practice should consider the potential adverse cognitive effects of ACB in the treatment decision-making process.

Cerebral and cerebellar correlates of social cognitive impairment in schizophrenia

Social cognition is a broad construct encompassing the ways in which individuals perceive, process, and use information about other people. Social cognition involves both lower- and higher-level processes such as emotion recognition and theory of mind, respectively. Social cognitive impairments have been repeatedly demonstrated in schizophrenia spectrum illnesses and, crucially, are related to functional outcomes. In this review, we summarize the literature investigating the brain networks implicated in social cognitive impairments in schizophrenia spectrum illnesses. In addition to cortical and limbic loci and networks, we also discuss evidence for cerebellar contributions to social cognitive impairment in this population. We conclude by synthesizing these two literatures, with an emphasis on current knowledge gaps, particularly in regard to cerebellar influences, and future directions.

Correlation study of brain-derived neurotrophic factor, EEG γ activity and cognitive function in first-episode schizophrenia

BackgroundSchizophrenia is characterised by neurotrophic, neuroelectrophysiological and cognitive dysfunction. However, there exists a paucity of research examining the association between serum brain-derived neurotrophic factor (BDNF) concentration, resting electroencephalogram (EEG) gamma activity, and cognitive impairment in individuals diagnosed with schizophrenia. MethodsIn this study, 87 first-episode schizophrenia patients and 75 healthy controls were assessed. Measurements were conducted to determine the levels of BDNF, resting EEG γ-activity at left and right frontal pole EEG electrodes respectively (FP1/FP2) leads, and cognitive function as assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery (MCCB). Comparisons were made between the patient group and the control group, revealing lower BDNF levels, lower T-scores for 7 MCCB cognitive items, and higher EEG γ-activity among patients when compared to controls. ResultsAccording to the correlation analysis, there were significant associations observed in the patient group. BDNF levels were found to be correlated with EEG γ activity as well as T-scores of speed of processing (SoP), verbal learning (VeL), and reasoning problem-solving (RPS). Moreover, EEG γ activity showed an association with both the total score of the Positive and Negative Syndrome Scale (PANSS) and T-score of SoP. These findings suggest a potential relationship between BDNF levels, EEG γ activity, cognitive domains, and clinical symptoms in individuals with first-episode schizophrenia. ConclusionsIn conclusion, our findings demonstrate the coexistence of neurobiochemical and electrophysiological abnormalities alongside cognitive dysfunction during the early stages of schizophrenia. These findings provide valuable insights into the mechanism of cognitive impairment in schizophrenia. By highlighting the simultaneous occurrence of these factors, our study contributes to a better understanding of the complex nature of schizophrenia and emphasizes the importance of studying its cognitive aspects.

Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptor agonist without antagonist activity at dopamine D2 or the serotonin 5-HT2A receptors, has demonstrated efficacy in the treatment of schizophrenia. Here we report the phase 1 translational studies that profiled the effect of ulotaront on brain responses to reward, working memory, and resting state connectivity (RSC) in individuals with low or high schizotypy (LS or HS). Participants were randomized to placebo (n = 32), ulotaront (50 mg; n = 30), or the D2 receptor antagonist amisulpride (400 mg; n = 34) 2 h prior to functional magnetic resonance imaging (fMRI) of blood oxygen level-dependent (BOLD) responses to task performance. Ulotaront increased subjective drowsiness, but reaction times were impaired by less than 10% and did not correlate with BOLD responses. In the Monetary Incentive Delay task (reward processing), ulotaront significantly modulated striatal responses to incentive cues, induced medial orbitofrontal responses, and prevented insula activation seen in HS subjects. In the N-Back working memory task, ulotaront modulated BOLD signals in brain regions associated with cognitive impairment in schizophrenia. Ulotaront did not show antidepressant-like biases in an emotion processing task. HS had significantly reduced connectivity in default, salience, and executive networks compared to LS participants and both drugs reduced this difference. Although performance impairment may have weakened or contributed to the fMRI findings, the profile of ulotaront on BOLD activations elicited by reward, memory, and resting state is compatible with an indirect modulation of dopaminergic function as indicated by preclinical studies. This phase 1 study supported the subsequent clinical proof of concept trial in people with schizophrenia.Clinical trial registration: Registry# and URL: ClinicalTrials.gov NCT01972711, https://clinicaltrials.gov/ct2/show/NCT01972711

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia.

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=-0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=-0.258, t=-2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=-0.247, p=0.019) and antipsychotic treatment duration (ρ=-0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.

Differential expression of diacylglycerol kinase ζ is involved in inferior parietal lobule-related dysfunction in schizophrenia with cognitive impairments

BackgroundCognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia.Methods136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects’ cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia.ResultsGrouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = − 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia.ConclusionOur study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.