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Thalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. 75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. No significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. Our findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. ClinicalTrials.gov NCT03965598 ; https://clinicaltrials.gov/ct2/show/NCT03965598. [ABSTRACT FROM AUTHOR]

Introduction: Patients with schizophrenia have a higher lifetime prevalence of suicidal behavior (SB) compared to the general population. Therefore, understanding the possible neurobiology of suicide and predicting the risk of suicide in schizophrenia is a solemnly critical issue. Methods: 31 drug-naïve first episode schizophrenia (FES) patients with current SB (FES-S), 69 drug-naive patients with first episode schizophrenia without SB (FES-NS), and 69 drug-naïve non-psychotic patients with current SB (NPS) who were diagnosed according to The Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) participated the study. The control group (HC) consisted of 127 individuals matched with the patients. Symptoms at the time of evaluation were assessed using The Positive and Negative Syndrome Scale (PANSS) and Columbia Suicide Severity Rating Scale (CSSRS). Blood samples were collected from all participants to determine White blood cell (WBC), neutrophil, monocyte, albumin, C-reactive protein (CRP), Lymphocyte, and Platelet levels and to measure this protein ratio. Results: The blood levels of WBC, neutrophil, monocyte, albumin, CRP, and Neutrophil/Albumin Ratio (NAR) were higher in all patient groups compared to HC. CRP/Albumin Ratio (CAR) value was observed to be highest in the NPS group. Monocyte/Lymphocyte Ratio (MLR) value was significantly higher in patients with FES compared to HC. There were no significant differences between the FES-S group and the FES-NS and NPS groups. Conclusion: It can be suggested that although inflammation is not a predictor for suicide attempts in schizophrenia, it is associated with the degree of suicide risk in schizophrenia. In addition, the strong relationship between suicide and psychiatric disorders can be the main reason for high peripheral inflammation levels in suicidal patients. [ABSTRACT FROM AUTHOR]

Abnormalities in cortical excitability and plasticity have been considered to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) can provide a direct evaluation of cortical responses to TMS. Here, we employed TMS-EEG to investigate cortical responses to orbitofrontal cortex (OFC) stimulation in schizophrenia. In total, we recruited 92 drug-naïve patients with first-episode schizophrenia and 51 age- and sex-matched healthy individuals. For each participant, one session of 1-Hz repetitive TMS (rTMS) was delivered to the right OFC, and TMS-EEG data were obtained to explore the change in cortical-evoked activities before and immediately after rTMS during the eyes-closed state. The MATRICS Consensus Cognitive Battery was used to assess neurocognitive performance. The cortical responses indexed by global mean field amplitudes (i.e., P30, N45, and P60) were larger in patients with schizophrenia than in healthy control participants at baseline. Furthermore, after one session of 1-Hz rTMS over the right OFC, the N100 amplitude was significantly reduced in the healthy control group but not in the schizophrenia group. In the healthy control participants, there was a significant correlation between modulation of P60 amplitude by rTMS and working memory; however, this correlation was absent in patients with schizophrenia. Aberrant global cortical responses following right OFC stimulation were found in patients with drug-naïve first-episode schizophrenia, supporting its significance in the primary pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of vascular endothelial growth factor (VEGF), insulin-like growth factor 1(IGF-1) and neuromodulatory protein 1(NRG1) on first-episode schizophrenia patients. Meth- ods A total of 71 patients with first-episode schizophrenia admitted to the hospital from September 2021 to January 2023 were retrospectively selected as the study group, and 71 healthy volunteers who underwent phys- ical examination during the same period were selected as the control group. At the same time, according to the results ofpositive and negative symptom scale (PANSS) score results, the study group was divided into the high score subgroup(70 points, 33 cases) and the low score subgroup (<70 points, 38 cases). The study group was divided into cognitive dysfunction group (29 cases) and normal cognitive function group (42 cases) according to the results of MATRICS recognized cognitive battery(MCCB). The levels of serum VEGF, IGF1, and NRG1 in each group were compared, and their correlation with MCCB and PANSS scores was analyzed. Results The levels of serum VEGF, IGF1, and NRG1 in the study group were lower than those in the control group, and the differences were statistically significant (P<0.05). The levels of serum VEGF, IGF1, and NRG1 in the cognitive dysfunction subgroup were lower than those in the normal cognitive function sub- group, and the differences were statistically significant (P<0.05). The levels of serum VEGF, IGF1, and NRG1 in the low score subgroup were higher than those in the high score subgroup, and the differences were statistically significant (P<0.05). The levels of serum VEGF, IGF1, and NRG1 were positively correlated with MCCB and PANSS scores (P<0.05). Conclusion The levels of serum VEGF, IGF1 and NRG1 in pa- tients with schizophrenia are lower than those in healthy people, which are closely related to mental symptoms and cognitive function. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) symptoms can be classified as positive and negative ones, each of which has distinct traits and possibly differences in gene expression and regulation. The co-expression networks linked to PANSS (Positive and Negative Syndrome Scale) scores were identified by weighted gene co-expression network analysis (WGCNA) using the expression profiles of miRNA and mRNA in the peripheral blood of first-episode SCZ patients. The heterogeneity between positive and negative symptoms was demonstrated using gene functional enrichment, gene-medication interaction, and immune cell composition analysis. Then, target gene prediction and correlation analysis of miRNA and mRNA constructed a symptom-related miRNA-mRNA regulatory network, screened regulatory pairs, and predicted binding sites. A total of six mRNA co-expression modules, two miRNA co-expression modules, and ten hub genes were screened to be significantly associated with positive symptoms; five mRNA co-expression modules and eight hub genes were correlated with negative symptoms. Positive symptom-related modules were significantly enriched in axon guidance, actin skeleton regulation, and sphingolipid signaling pathway, while negative symptom-related modules were significantly enriched in adaptive immune response, leukocyte migration, dopaminergic synapses, etc. The development of positive symptoms may have been influenced by potential regulatory pairings such as miR-98-5p-EIF3J, miR-98-5p-SOCS4, let-7b-5p-CLUH, miR-454-3p-GTF2H1, and let-7b-5p-SNX17. Additionally, immune cells were substantially connected with several hub genes for symptoms. Positive and negative symptoms in SCZ individuals were heterogeneous to some extent. miRNAs such as let-7b-5p and miR-98-5p might contribute to the incidence of positive symptoms by targeting mRNAs, while the immune system's role in developing negative symptoms may be more nuanced. [ABSTRACT FROM AUTHOR]

Gamma-band activity has been the focus of considerable research in schizophrenia. Discrepancies exist regarding the integrity of the early auditory gamma-band response (EAGBR), a stimulus-evoked oscillation, and its relationship to symptoms in early disease. Variability in task design may play a role. This study examined sensitivity of the EAGBR to stimulus intensity and its relation to symptoms and functional impairments in the first-episode schizophrenia spectrum (FESz). Magnetoencephalography was recorded from 35 FESz and 40 matched healthy controls (HC) during presentation of 3 tone intensities (75 dB, 80 dB, 85 dB). MRIs were collected to localize auditory cortex activity. Wavelet-transformed single trial epochs and trial averages were used to assess EAGBR intertrial phase coherence (ITPC) and evoked power, respectively. Symptoms were assessed using the Positive and Negative Syndrome Scale. Groups did not differ in overall EAGBR power or ITPC. While HC exhibited EAGBR enhancement to increasing intensity, FESz exhibited reduced power to the 80 dB tone and, relative to HC, increased power to the 75 dB tone. Larger power and ITPC were correlated with more severe negative, thought disorganization, and resistance symptoms. Stronger ITPC was associated with impaired social functioning. EAGBR showed no overall deficit at disease onset. Rather, FESz exhibited a differential response across tone intensity relative to HC, emphasizing the importance of stimulus characteristics in EAGBR studies. Associations between larger EAGBR and more severe symptoms suggest aberrant synchronization driving overinclusive perceptual binding that may relate to deficits in executive inhibition of initial sensory activity. [ABSTRACT FROM AUTHOR]

Abstract Background Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. Methods We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. Results Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. Conclusion Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.

Introduction: It is known that cognitive deficits are a core feature of schizophrenia and that in the general population, prior beliefs significantly influence learning and reasoning processes. However, the interaction of prior beliefs with cognitive deficits and their impact on performance in schizophrenia patients is still poorly understood. This study investigates the role of beliefs and cognitive variables (CVs) like working memory, associative learning, and processing speed on learning processes in individuals with schizophrenia. We hypothesize that beliefs will influence the ability to learn correct predictions and that first-episode schizophrenia patients (FEP) will show impaired learning due to cognitive deficits. Methods: We used a predictive-learning task to examine how FEP (n = 23) and matched controls (n = 23) adjusted their decisional criteria concerning physical properties during the learning process when predicting the sinking behavior of two transparent containers filled with aluminum discs when placed in water. Results: On accuracy, initial differences by group, trial type, and interaction effects of these variables disappeared when CVs were controlled. The differences by conditions, associated with differential beliefs about why the objects sink slower or faster, were seen in patients and controls, despite controlling the CVs' effect. Conclusions: Differences between groups were mainly explained by CVs, proving that they play an important role than what is assumed in this type of task. However, beliefs about physical events were not affected by CVs, and beliefs affect in the same way the decisional criteria of the control or FEP patients' groups.

Background: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. Methods: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. Results: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. Conclusion: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms. Significant outcomes: •Ventricular shrinkage is as frequent as ventricular enlargement in the early course of the disease. •Ventricular enlargement is associated with the severity of negative symptoms. Limitations •MRI scans were taken at only two time points, which may not capture the full range of changes in ventricular volume that occur throughout the illness. •Not all possible confounding factors that might affect VV changes (such as exposure to infectious agents, smoking, medical comorbidities, and polytherapy) were involved. [ABSTRACT FROM AUTHOR]

We aimed to examine the hypotheses that glucolipid metabolism is linked to neurocognition and gray matter volume (GMV) and that GMV mediates the association of glucolipid metabolism with neurocognition in first-episode, drug-naïve (FEDN) patients with schizophrenia. Parameters of glucolipid metabolism, neurocognition, and magnetic resonance imaging were assessed in 63 patients and 31 controls. Compared to controls, patients exhibited higher levels of fasting glucose, triglyceride, and insulin resistance index, lower levels of cholesterol and high-density lipoprotein cholesterol, poorer neurocognitive functions, and decreased GMV in the bilateral insula, left middle occipital gyrus, and left postcentral gyrus. In the patient group, triglyceride levels and the insulin resistance index exhibited a negative correlation with Rapid Visual Information Processing (RVP) mean latency, a measure of attention within the Cambridge Neurocognitive Test Automated Battery (CANTAB), while showing a positive association with GMV in the right insula. The mediation model revealed that triglyceride and insulin resistance index had a significant positive indirect (mediated) influence on RVP mean latency through GMV in the right insula. Glucolipid metabolism was linked to both neurocognitive functions and GMV in FEDN patients with schizophrenia, with the effect pattern differing from that observed in chronic schizophrenia or schizophrenia comorbid with metabolic syndrome. Moreover, glucolipid metabolism might indirectly contribute to neurocognitive deficits through the mediating role of GMV in these patients. • Dysregulated glucolipid metabolism existed in FEDN schizophrenia. • Glucolipid metabolism was associated with neurocognition in FEDN schizophrenia. • Monitoring glucolipid metabolism in the early stages of schizophrenia. [ABSTRACT FROM AUTHOR]

Stress plays an important role in the etiology of schizophrenia. However, the mechanisms by which chronic physiological stress and perceived stress relate to the clinical features of schizophrenia may differ. We aimed to elucidate the relationships among chronic physiological stress indexed by allostatic load (AL), perceived stress, and clinical symptoms in individuals with first-episode schizophrenia (FES). Individuals with FES (n = 90, mean age = 28.26years old, 49%female) and healthy controls (111, 28.88, 51%) were recruited. We collected data of 13 biological indicators to calculate the AL index, assessed subjective stress with the Perceived Stress Scale-14 (PSS-14), and compared AL and perceived stress between groups. Patients with FES were also evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). Individuals with FES had higher AL and PSS score than healthy controls. There were no significant correlations between AL and PSS score in either patients or controls. Among individuals with FES, the AL index was associated with the severity of positive symptoms, while the PSS score was positively associated with CDSS score. Both elevated AL and PSS were correlated with the occurrence of schizophrenia. Physiological stress, as reflected by AL, may be more related to positive symptoms, while perceived stress appear to be associated with depressive symptoms in individuals with FES. Longitudinal studies are necessary to explore the relationships between interventions for different stressor types and specific clinical outcomes in FES. [ABSTRACT FROM AUTHOR]

Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments. [ABSTRACT FROM AUTHOR]

Rationale: An imbalance of the tryptophan kynurenine pathway (KP) commonly occurs in psychiatric disorders, though the neurocognitive and network-level effects of this aberration are unclear. Objectives: In this study, we examined the connection between dysfunction in the frontostriatal brain circuits, imbalances in the tryptophan kynurenine pathway (KP), and neurocognition in major psychiatric disorders. Methods: Forty first-episode medication-naive patients with schizophrenia (SCZ), fifty patients with bipolar disorder (BD), fifty patients with major depressive disorder (MDD), and forty-two healthy controls underwent resting-state functional magnetic resonance imaging. Plasma levels of KP metabolites were measured, and neurocognitive function was evaluated. Frontostriatal connectivity and KP metabolites were compared between groups while controlling for demographic and clinical characteristics. Canonical correlation analyses were conducted to explore multidimensional relationships between frontostriatal circuits-KP and KP-cognitive features. Results: Patient groups shared hypoconnectivity between bilateral ventrolateral prefrontal cortex (vlPFC) and left insula, with disorder-specific dysconnectivity in SCZ related to PFC, left dorsal striatum hypoconnectivity. The BD group had higher anthranilic acid and lower xanthurenic acid levels than the other groups. KP metabolites and ratios related to disrupted frontostriatal dysconnectivity in a transdiagnostic manner. The SCZ group and MDD group separately had high-dimensional associations between KP metabolites and cognitive measures. Conclusions: The findings suggest that KP may influence cognitive performance across psychiatric conditions via frontostriatal dysfunction. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Visual fixation is a dynamic process, with the spontaneous occurrence of microsaccades and macrosaccades. These fixational saccades are sensitive to the structural and functional alterations of the cortical-subcortical-cerebellar circuit. Given that dysfunctional cortical-subcortical-cerebellar circuit contributes to cognitive and behavioral impairments in schizophrenia, we hypothesized that patients with schizophrenia would exhibit abnormal fixational saccades and these abnormalities would be associated with the clinical manifestations. Study Design Saccades were recorded from 140 drug-naïve patients with first-episode schizophrenia and 160 age-matched healthy controls during ten separate trials of 6-second steady fixations. Positive and negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Study Results Patients with schizophrenia exhibited fixational saccades more vertically than controls, which was reflected in more vertical saccades with angles around 90° and a greater vertical shift of horizontal saccades with angles around 0° in patients. The fixational saccades, especially horizontal saccades, showed longer durations, faster peak velocities, and larger amplitudes in patients. Furthermore, the greater vertical shift of horizontal saccades was associated with higher PANSS total and positive symptom scores in patients, and the longer duration of horizontal saccades was associated with lower MCCB neurocognitive composite, attention/vigilance, and speed of processing scores. Finally, based solely on these fixational eye movements, a K-nearest neighbors model classified patients with an accuracy of 85%. Conclusions: Our results reveal spatial and temporal abnormalities of fixational saccades and suggest fixational saccades as a promising biomarker for cognitive and positive symptoms and for diagnosis of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. Aims: We aimed to identify factors from the baseline visit (V1) — with a mean illness duration of 0.47 years (SD = 0.45) — that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/− 0.45). Method: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. Results: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p

Abstract Background Identifying the characteristic neurobiological changes of early psychosis is helpful for early clinical diagnosis. However, previous studies on the brain electrophysiology of children and adolescents with psychosis are rare. Methods This study compared P300 amplitude at multiple electrodes between children and adolescents with first-episode schizophrenia (FES, n = 48), children and adolescents with psychosis risk syndrome (PRS, n = 24), and healthy controls (HC, n = 30). Receiver operating characteristic (ROC) analysis was used to test the ability of P300 amplitude to distinguish FES, PRS and HC individuals. Results The P300 amplitude in the FES group were significantly lower than those in the HC at the Cz, Pz, and Oz electrodes. The P300 amplitude was also significantly lower in the prodromal group than in the HC at the Pz and Oz electrodes. ROC curve analysis showed that at the Pz electrode, the P300 amplitude evoked by the target and standard stimulus showed high sensitivity, specificity, accuracy, and area under the curve value for distinguishing FES from HC individuals. Conclusions This study found early visual P300 deficits in children and adolescents with FES and PRS, with the exclusion of possible influence of medication and chronic medical conditions, suggesting the value of P300 amplitude for the identification of early psychosis.

Abstract Background Schizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms. Methods Seventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman’s correlation and stepwise linear regression were used to analyze the data. Results Serum interleukin-1β and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1β levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1β levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1β levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1β and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively. Conclusion Our results showed that patients with first-episode SCZ have low-grade inflammation. IL-1β and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population. Trial registration The clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343.

Background: Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement. Methods: We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale. Results: Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome. Conclusions: The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis. [ABSTRACT FROM AUTHOR]

Background: Identifying the characteristic neurobiological changes of early psychosis is helpful for early clinical diagnosis. However, previous studies on the brain electrophysiology of children and adolescents with psychosis are rare. Methods: This study compared P300 amplitude at multiple electrodes between children and adolescents with first-episode schizophrenia (FES, n = 48), children and adolescents with psychosis risk syndrome (PRS, n = 24), and healthy controls (HC, n = 30). Receiver operating characteristic (ROC) analysis was used to test the ability of P300 amplitude to distinguish FES, PRS and HC individuals. Results: The P300 amplitude in the FES group were significantly lower than those in the HC at the Cz, Pz, and Oz electrodes. The P300 amplitude was also significantly lower in the prodromal group than in the HC at the Pz and Oz electrodes. ROC curve analysis showed that at the Pz electrode, the P300 amplitude evoked by the target and standard stimulus showed high sensitivity, specificity, accuracy, and area under the curve value for distinguishing FES from HC individuals. Conclusions: This study found early visual P300 deficits in children and adolescents with FES and PRS, with the exclusion of possible influence of medication and chronic medical conditions, suggesting the value of P300 amplitude for the identification of early psychosis. [ABSTRACT FROM AUTHOR]

Aim: Many individuals with schizophrenia discontinue initially prescribed antipsychotics. Knowledge on reasons for discontinuation among individuals with first‐episode schizophrenia is sparse. We aimed to describe reasons for discontinuation and continuation, differences between individuals discontinuing and continuing, and factors predicting reasons for discontinuation or continuation. Methods: This was a prospective cohort study with a post hoc design. Individuals with first‐episode schizophrenia were included from early intervention teams in Denmark from 2009–2012. Sociodemographic and clinical variables were collected at baseline and reasons for discontinuation and continuation of antipsychotics were assessed at 3.5‐year follow‐up. Results: Among 215 patients, 76 reported reasons for discontinuation and 139 for continuation. The most frequent reasons for discontinuation were "side effects" and "patient believed he/she no longer needed the medication because he/she was now better". The most frequent reasons for continuation were "benefits for positive symptoms" and "another person told them to". Individuals who discontinued antipsychotics were at baseline younger, had longer DUP, less negative symptoms, better social function, lower compliance, higher self‐belief of coping, and fewer used antipsychotics compared to those continuing antipsychotics. Conclusions: The effect of antipsychotics is the main reason to continue, whereas side effects were the main reason to discontinue. Knowledge of reasons to discontinue or continue is helpful in shared decision‐making, identifying individuals with high odds of discontinuation, improving adherence, and helping with safe discontinuation. [ABSTRACT FROM AUTHOR]

The mapping of cognitive trajectories after a first episode of schizophrenia has been the aim in several studies, but the longitudinal course of cognitive impairments remains an important question. Due to methodological limitations, it has been challenging to pinpoint specific periods of improvement or stability in cognitive functioning over time. The objective of this study is to further clarify the longitudinal course of cognitive change after a first episode of schizophrenia through frequent repeated measurement. A total of 56 persons participated in the study (28 first episode patients and 28 healthy pairwise matched controls) with 79 % of patients retained at the 10-year follow-up. The Oslo Schizophrenia Recovery study has a repeated measurement design and includes data from nine cognitive assessments over 10 years. Cognition was assessed with the MATRICS Consensus Cognitive Battery, which is well suited for repeated measurements. Data were analyzed with linear multilevel models. The results challenge some of the views about the course of cognitive impairment in first-episode schizophrenia patients. Using quadratic time effects in our analyses and balancing the patient group with regards to the most relevant confounding demographic variables such as age, gender, and education, we showed that cognitive deficits change and improve more than in healthy individuals until year 6, when both groups stabilize. The patient group improved on some of the most important cognitive domains associated with functional outcome with 63.5 % full recovery at 10-year follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Nonadherence to treatment is a recognized problem and the most challenging aspect of treatment, particularly in first‑episode schizophrenia (FES). We aimed to identify a set of individuals in the social milieu of patients as opinion makers who play significant role in influencing treatment‑seeking behavior in patients with FES. Materials and Methods: Patients with a diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fifth edition), first episode, were administered with a 20 items semi‑structured questionnaire to identify the individuals and their role in treatment‑seeking behavior of patients with FES. Results: A total of 72 patients were enrolled in the study. The mean age of the sample was 29 years (standard deviation [SD] ±7.35), and the mean duration of illness was 9.2 (SD ± 0.58) months. Our study shows that apart from treating psychiatrists, patient’s family members and relatives play a crucial role in influencing treatment‑seeking behavior such as treatment commencement, drug dose, formulation, place of treatment, etc., A large number of patients went to faith healers on the advice of family members (34.7%) and also followed the advice of family members regarding the duration of treatment (63.3%) as well as discontinuing treatment (63.3%). Conclusion: The index study concludes the role of family members/relatives as opinion makers in the social milieu of patients with FES in influencing treatment‑related decisions and affecting adherence to treatment. [ABSTRACT FROM AUTHOR]

Introduction: Elevated proinflammatory status and alterations in blood flow, both of which are associated with the pathophysiology of schizophrenia, may be linked with an increased risk of cardiovascular diseases. However, such a relationship at different acute stages of schizophrenia has not been evaluated. We aimed to examine whether blood viscosity and systemic inflammatory status varied between firstepisode schizophrenia (FES) and acute exacerbations of schizophrenia. Methods: Fifty-two patients with FES, 69 schizophrenia patients with acute exacerbation (S-AE) and 56 healthy controls (HC) were included in the study. Whole blood viscosity (WBV) was calculated according to de Simone's formula at low and high shear rates (LSR and HSR). Systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) were calculated from hemogram screening data at admission. Results: When adjusted for age, WBV at both LSR and HSR were significantly decreased in both FES and S-AE groups compared to HCs. Systemic inflammatory response index was significantly higher in FES patients than in the S-AE and HC groups. Total cholesterol (TC) and WBV at HSR were correlated in patients. Total cholesterol predicted WBV at LSR in patients with FES whereas other independent variables including age and SIRI did not. Conclusion: Both first and subsequent episodes of schizophrenia are associated with reduced blood viscosity. Increased inflammatory status may not fully explain such a relationship. Extrapolation of hemorheological characteristics in schizophrenia may help to stratify cardiovascular risk and reflect the pathophysiological process in the early and later stages of schizophrenia. [ABSTRACT FROM AUTHOR]

Introduction: Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). Materials and methods: This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Results: Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). Discussion: The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology. [ABSTRACT FROM AUTHOR]

Background: Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death. Methods: Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995–2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2–5. Outcomes year 5–6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression. Results: Among 21 351, 9.3% took antipsychotics continuously year 2–5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53–2.56 and OR 2.60, 95% CI 1.91–3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05–1.48 and 2.04, 95% CI 1.64–2.53) and no antipsychotics (OR 2.00, 95% CI 1.69–2.38 and 5.64, 95% CI 4.56–6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10–1.47) and longer admissions (IRR 1.68, 95% CI 1.30–2.16) year 5–6 compared to continuous users. Mortality during year 5–6 did not differ between groups. Conclusion: Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms. Methods: Seventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman's correlation and stepwise linear regression were used to analyze the data. Results: Serum interleukin-1β and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1β levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1β levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1β levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1β and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively. Conclusion: Our results showed that patients with first-episode SCZ have low-grade inflammation. IL-1β and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population. Trial registration: The clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343. [ABSTRACT FROM AUTHOR]

Background and Purpose: The detection and characterization of functional activities in the gray matter of schizophrenia (SZ) have been widely explored. However, the relationship between resting‐state functional signals in the white matter of first‐episode SZ and short‐term treatment response remains unclear. Methods: Thirty‐six patients with first‐episode SZ and 44 matched healthy controls were recruited in this study. Patients were classified as nonresponders and responders based on response to antipsychotic medication during a single hospitalization. The fractional amplitude of low‐frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) of white matter were calculated. The relationships between functional changes and clinical features were analyzed. In addition, voxel‐based morphometry was performed to analyze the white matter volume. Results: One‐way analysis of variance showed significant differences of fALFF and ReHo in the left posterior thalamic radiation and left cingulum (hippocampus) in the patient group, and the areas were regarded as seeds. The FC was calculated between seeds and other white matter networks. Compared with responders, nonresponders showed significantly increased FC between the left cingulum (hippocampus) and left posterior thalamic radiation, splenium of corpus callosum, and left tapetum, and were associated with the changes of clinical assessment. However, there was no difference in white matter volume between groups. Conclusion: Our work provides a novel insight that psycho‐neuroimaging‐based white matter function holds promise for influencing the clinical diagnosis and treatment of SZ. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. Methods: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. Results: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)–left inferior temporal gyrus (ITG), right IFG–left ITG, right IFG–left middle frontal gyrus (MFG), and right IFG–right MFG in the FES group. Conclusion: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions. [ABSTRACT FROM AUTHOR]

Delay discounting (DD) is the phenomenon of individuals discounting future rewards as a function of time. It has been studied extensively in chronic schizophrenia (SZ) and the results of these studies have been variable. Comorbidity in chronic samples could be one reason for the mixed findings and studies in first-episode (FE) samples are surprisingly lacking. Bipolar disorder (BP) which shares some genetic and symptom features with SZ could serve as an interesting comparison group for DD but has been underexplored. Here we present the first study that combines FE SZ, FE BP with psychotic features, as well as healthy controls and study DD with two versions of the task. We found that SZ showed steeper discounting than HC and BP on the well-validated Kirby DD task. SZ showed no difference than HC on a separate DD task with smaller rewards presented with decimal places and shorter delays. As a preliminary finding, DD was found to be positively related to positive symptoms in FE SZ, while no relationship was found between negative symptoms and DD. In addition, we found comparable DD in BP compared to HC. Ultimately, our data may help elucidate the psychopathology in SZ and BP during intertemporal decision making.

BACKGROUND: This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling. METHODS: Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication. RESULTS: The IPS-WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS-WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS-WFM intervention (45 v. 26 weeks, p < 0.004). CONCLUSIONS: The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

BackgroundReward processing abnormalities may underlie characteristic pleasure and motivational impairments in schizophrenia. Some neural measures of reward processing show age-related modulation, highlighting the importance of considering age effects on reward sensitivity. We compared event-related potentials (ERPs) reflecting reward anticipation (stimulus-preceding negativity, SPN) and evaluation (reward positivity, RewP; late positive potential, LPP) across individuals with schizophrenia (SZ) and healthy controls (HC), with an emphasis on examining the effects of chronological age, brain age (i.e., predicted age based on neurobiological measures), and illness phase.MethodsSubjects underwent EEG while completing a slot-machine task for which rewards were not dependent on performance accuracy, speed, or response preparation. Slot-machine task EEG responses were compared between 54 SZ and 54 HC individuals, ages 19 to 65. Reward-related ERPs were analyzed with respect to chronological age, categorically-defined illness phase (early; ESZ versus chronic schizophrenia; CSZ), and were used to model brain age relative to chronological age.ResultsIllness phase-focused analyses indicated there were no group differences in average SPN or RewP amplitudes. However, a group × reward outcome interaction revealed that ESZ differed from HC in later outcome processing, reflected by greater LPP responses following loss versus reward (a reversal of the HC pattern). While brain age estimates did not differ among groups, depressive symptoms in SZ were associated with older brain age estimates while controlling for negative symptoms.ConclusionsESZ and CSZ did not differ from HC in reward anticipation or early outcome processing during a cognitively undemanding reward task, highlighting areas of preserved functioning. However, ESZ showed altered later reward outcome evaluation, pointing to selective reward deficits during the early illness phase of schizophrenia. Further, an association between ERP-derived brain age and depressive symptoms in SZ extends prior findings linking depression with reward-related ERP blunting. Taken together, both illness phase and age may impact reward processing among SZ, and brain aging may offer a promising, novel marker of reward dysfunction that warrants further study.

Background: Nonadherence to treatment is a recognized problem and the most challenging aspect of treatment, particularly in first-episode schizophrenia (FES). We aimed to identify a set of individuals in the social milieu of patients as opinion makers who play significant role in influencing treatment-seeking behavior in patients with FES. Materials and Methods: Patients with a diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, fifth edition), first episode, were administered with a 20 items semi-structured questionnaire to identify the individuals and their role in treatment-seeking behavior of patients with FES. Results: A total of 72 patients were enrolled in the study. The mean age of the sample was 29 years (standard deviation [SD] ±7.35), and the mean duration of illness was 9.2 (SD ± 0.58) months. Our study shows that apart from treating psychiatrists, patient's family members and relatives play a crucial role in influencing treatment-seeking behavior such as treatment commencement, drug dose, formulation, place of treatment, etc., A large number of patients went to faith healers on the advice of family members (34.7%) and also followed the advice of family members regarding the duration of treatment (63.3%) as well as discontinuing treatment (63.3%). Conclusion: The index study concludes the role of family members/relatives as opinion makers in the social milieu of patients with FES in influencing treatment-related decisions and affecting adherence to treatment.

Studies indicate that people with schizophrenia experience deficits in their ability to accurately detect emotions, both through facial expressions and voice intonation (i.e., prosody), and that functioning and symptoms are associated with these deficits. This study aimed to examine how facial emotion and affective prosody recognition are related to functioning and symptoms in a first-episode schizophrenia sample. Further, in light of research suggesting variable emotion-specific performance in people with schizophrenia, this study explored emotion-specific performance. Participants were 49 people with a recent first episode of schizophrenia taking part in a larger RCT. Results revealed that affective prosody recognition was significantly correlated with both role and social functioning. Regarding associations with psychiatric symptoms, facial emotion recognition was significantly, negatively associated with all three positive symptom scales, whereas affective prosody recognition was significantly, negatively associated with disorganization only. Emotion-specific analyses revealed that for affective prosody, participants were most accurate in recognizing anger and least accurate for disgust. For facial emotion recognition, participants were most accurate in recognizing happiness and least accurate for fear. Taken together, results suggest that affective prosody recognition is important for social and role functioning in people with first-episode schizophrenia. Results also suggest that this group may struggle more to identify negative emotions, though additional work is needed to clarify this pattern in affective prosody and determine real-world impact on social interactions.

ObjectiveTo explore the effects of group interpersonal psychotherapy （IPT） on cognitive and social function in patients with first-episode schizophrenia， and to provide references for appropriate psychological treatment for the patients.MethodsA total of 62 patients with first-episode schizophrenia who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） and were admitted to the Third People's Hospital of Foshan from January to December 2021 were selected as the study objects. And patients were divided into study group and control group according to random number table method， each with 31 cases. Both groups were treated with risperidone for 8 weeks， based on this， study group received group IPT. Before and after 8 weeks of treatment， Positive and Negative Syndrorne Scales （PANSS）， Wisconsin Card Sorting Tests （WCST） and Personal and Social Performance Sale（PSP） were adopted to assess the patients' psychiatric symptoms， cognitive function and social function.ResultsAfter 8 weeks of treatment， there was no significant difference in PANSS scores between the two groups （t=0.296， P>0.05）. The WCST total number of responses in the study group was larger than that in the control group， the number of perseverative errors and non-perseverative errors were smaller than those in the control group， and PSP score of the study group was higher than that of the control group， with statistically significant differences （t=0.398， 2.609， 0.523， 0.381， P

Abstract Background Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. Methods The South Korean Health Insurance Review Agency database (2012–2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. Results Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p

Aberrant resting-state functional connectivity (FC) of anterior cingulate cortex (ACC) has been implicated in the pathophysiology of schizophrenia and bipolar disorder (BP). This study investigated the subregional FC of ACC across schizophrenia and psychotic (PBP) and nonpsychotic BP (NPBP) and the relationship between brain functional alterations and clinical manifestations. A total of 174 first-episode medication-naive patients with schizophrenia (FES), 80 patients with PBP, 77 patients with NPBP and 173 demographically matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Brain-wide FC of ACC subregions was computed for each individual, and compared between the groups. General intelligence was evaluated using the short version of the Wechsler Adult Intelligence Scale. Relationships between FC and various clinical and cognitive variables were estimated using the skipped correlation. The FES, PBP and NPBP groups showed differing connectivity patterns in the left caudal, dorsal and perigenual ACC. Transdiagnostic dysconnectivity was found in the subregional ACC associated with cortical, limbic, striatal and cerebellar regions. Disorder-specific dysconnectivity in FES was identified between the left perigenual ACC and bilateral orbitofrontal cortex, and the left caudal ACC coupling with the default mode network (DMN) and visual processing region was correlated with psychotic symptoms. In the PBP group, FC between the left dorsal ACC and the right caudate was correlated with psychotic symptoms, and FC connected with the DMN was associated with affective symptoms. The current findings confirmed that subregional ACC dysconnectivity could be a key transdiagnostic feature and associated with differing clinical symptomology across schizophrenia and PBP. [ABSTRACT FROM AUTHOR]

Aim: While patients with schizophrenia are more likely to be victims rather than perpetrators of aggressive behaviour, prior research has shown increased rates of aggressive behaviours in these patients that appear very early in the course of illness. We aimed to assess aggression in antipsychotic‐naive first‐episode schizophrenia patients, their healthy siblings, and controls; and to investigate correlates of aggression in the patients group. Methods: Patients (N = 55), siblings (N = 55) and healthy controls (N = 71) were evaluated on Buss and Perry Aggression Questionnaire (AQ), Life History of Aggression (LHA), Barratt Impulsiveness Scale, and Levenson Self‐Report Psychopathy Scale. Age, gender and substance use were regarded as covariates, and differences between the three groups were evaluated using analysis of covariance. Hierarchical regression was performed to determine which variables were associated with aggression level in the patients group. Results: The Tukey multiple comparison test showed that both patients (p <.001) and siblings (p =.023) scored higher on the LHA Aggression than controls. Siblings scored higher than controls (p =.010) for the Anger subscale of the AQ. Patients scored significantly higher than controls in the three impulsiveness dimensions; whereas siblings scored higher than controls in the motor (p =.023) and non‐planning (p =.004) dimensions. Multivariate analyses showed that, after controlling for confounders, only attentional impulsiveness (β =.446, p =.0244) and psychopathy traits (β =.359, p =.010) helped predict AQ total scores among patients. Conclusion: Aggression and some of its risk factors including impulsiveness are likely to be trait variables that might provide important vulnerability markers for people at heightened risk of developing psychosis. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Through decades the clinical recovery outcomes among individuals diagnosed with schizophrenia have been highly inconsistent ranging from 13.5% to 57%. The primary objective of this updated examination was to report the pooled estimate and explore various moderators to improve the understanding of the course of schizophrenia. Study Design A systematic literature search was set up on PubMed, PsycInfo, and EMBASE until January 13th, 2022. Both observational and interventional studies among cohorts of individuals with the first episode of schizophrenia reporting on clinical recovery were included. The PRISMA 2020 statement was used and data was extracted for a random-effects meta-analysis, meta-regression, and sensitivity analyses. Risk of bias was assessed using The Newcastle-Ottawa Scale. Study Results A 20.8% (95% CI = 17.3 to 24.8) recovery rate was found among 26 unique study samples (mean trial duration, 9.5 years) including 3877 individuals (mean age, 26.4 years). In meta-regression none of the following study characteristics could uncover the diverse reported recovery rates; age at inclusion (P =.84), year of inclusion (P =.93), follow-up time (P =.99), drop-out rate (P =.07), or strictness of the recovery criteria (P =.35). Furthermore, no differences in recovery were found between early intervention services (EIS; 19.5%; 95% CI = 15.0 to 24.8) compared to other interventions (21%; 95% CI = 16.9 to 25.8), P =.65. Conclusions A clinical recovery rate of approximately 21% was found with minimum impact from various moderators. The rate was not different comparing EIS with other interventions implying that new initiatives are needed to improve the rate of recovery. [ABSTRACT FROM AUTHOR]

Response inhibition (RI) is a component of the cognitive control systems that support optimal cognition. Cognitive control deficits are well-described in schizophrenia, but are not well characterized in individuals at clinical high risk (CHR) for developing psychosis. Functional magnetic resonance imaging during Go/NoGo task performance was collected from 30 CHR youth, 23 early illness schizophrenia patients (ESZ), and 72 healthy adolescents and young adults (HC). Voxelwise main effects of group were examined (P < .005 height threshold, family-wise error-corrected cluster threshold, P < .05) for correct NoGo-Go contrast values and task-based functional connectivity. CHR and ESZ groups had slower and more variable reaction times (RT) on Go trials compared to HCs. Significant main effects of group in bilateral dorsal anterior cingulate (dACC) and right inferior frontal cortex stemmed from CHR and ESZ groups showing significantly less NoGo-Go activation, relative to HCs. Faster responding HCs had less functional coupling between dACC and medial prefrontal cortex, a default mode network (DMN) region during NoGo vs Go trials. This functional connectivity-performance relationship was not present in ESZ or CHR groups. The pattern of findings suggests CHR and ESZ groups were deficient in developing strong and consistent prepotent responding, based on their slow and variable motor responses and decreased engagement of dACC and right inferior frontal regions implicated in inhibitory control. Furthermore, only the control group showed a functional connectivity relationship consistent with greater response prepotency requiring more decoupling of inhibitory control regions from DMN regions during RI.

Introduction: Abnormalities of the cerebellum have been displayed to be a manifestation of schizophrenia (SCH) which is a detrimental psychiatric disorder. It has been recognized that the cerebellum contributes to motor function, sensorimotor function, cognition, and other brain functions in association with cerebral functions. Multiple studies have observed that abnormal alterations in cerebro-cerebellar functional connectivity (FC) were shown in patients with SCH. However, the FC of cerebellar networks in SCH remains unclear. Methods: In this study, we explored the FC of cerebellar networks of 45 patients with first-episode SCH and 45 healthy control (HC) subjects by using a defined Yeo 17 network parcellation system. Furthermore, we performed a correlation analysis between cerebellar networks' FC and positive and negative symptoms in patients with first-episode SCH. Finally, we established the classification model to provide relatively suitable features for patients with first-episode SCH concerning the cerebellar networks. Results:We found lower between-network FCs between 14 distinct cerebellar network pairs in patients with first-episode SCH, compared to the HCs. Significantly, the between-network FC in N2-N15 was positively associated with positive symptom severity; meanwhile, N4-N15 was negatively associated with negative symptom severity. Besides, our results revealed a satisfactory classification accuracy (79%) of these decreased between-network FCs of cerebellar networks for correctly identifying patients with first-episode SCH. Conclusion: Conclusively, between-network abnormalities in the cerebellum are closely related to positive and negative symptoms of patients with firstepisode SCH. In addition, the classification results suggest that the cerebellar networks can be a potential target for further elucidating the underlying mechanisms in first-episode SCH. [ABSTRACT FROM AUTHOR]

To explore the effects of group interpersonal psychotherapy (IPT) on cognitive and social function in patients with first-episode schizophrenia， and to provide references for appropriate psychological treatment for the patients. Methods A total of 62 patients with first-episode schizophrenia who met the diagnostic criteria of International Classification of Diseases， tenth edition (ICD-10) and were admitted to the Third People's Hospital of Foshan from January to December 2021 were selected as the study objects. And patients were divided into study group and control group according to random number table method， each with 31 cases. Both groups were treated with risperidone for 8 weeks， based on this， study group received group IPT. Before and after 8 weeks of treatment， Positive and Negative Syndrorne Scales (PANSS)， Wisconsin Card Sorting Tests (WCST) and Personal and Social Performance Sale (PSP) were adopted to assess the patients' psychiatric symptoms， cognitive function and social function. Results After 8 weeks of treatment， there was no significant difference in PANSS scores between the two groups (t=0. 296，P>0. 05). The WCST total number of responses in the study group was larger than that in the control group， the number of perseverative errors and non-perseverative errors were smaller than those in the control group， and PSP score of the study group was higher than that of the control group， with statistically significant differences (t=0. 398，2. 609，0. 523，0. 381，P<0. 05 or 0. 01). Conclusion Group IPT may have no significant efficacy on alleviating the symptoms of patients with first-episode schizophrenia， but it may help improve the cognitive and social function in patients. [ABSTRACT FROM AUTHOR]

The prevalence of treatment-resistant schizophrenia (TRS) among people with first-episode schizophrenia (FES) has been sub-optimally researched in Australia and internationally. We evaluated the prevalence of TRS among a cohort of FES patients and compared their sociodemographic and clinical characteristics to those with FES who were treatment responsive.Over 2 years, we collated demographic, clinical and treatment-related data of all patients with ICD-10 (International Classification of Diseases, Tenth revision) diagnosis of schizophrenia who were active in October 2020 at four early psychosis intervention services (EPIS) in Western Australia. We used a modified version of Suzuki et al. criteria to diagnose TRS. The data were analysed utilising descriptive statistics, the Mann–Whitney U test, Student’s t-test and the False-Discovery Rate method.The prevalence of TRS among the 167 patients diagnosed with FES was 41.3%, and the rates did not differ significantly between the services (p = 0.955). Those in the TRS group were less independent (p = 0.011), had more prolonged unemployment (p = 0.014) and were more likely to be on disability pension (p = 0.011) compared to the treatment responsive group. Furthermore, they had greater severity of symptoms (p = 0.002), longer duration of psychiatric symptoms (p = 0.019), more hospitalisations (p = 0.002) and longer cumulative admission durations (p = 0.002).Our study revealed that treatment resistance to antipsychotics is prevalent among people with FES managed at EPIS. Notably, it establishes an association between TRS and heightened clinical severity and psychosocial and treatment burden. These findings highlight the imperative for early detection of treatment resistance and timely and specialised interventions for this condition in mental health services. [ABSTRACT FROM AUTHOR]

Schizophrenia is believed to be a developmental disorder with one hypothesis suggesting that symptoms arise due to abnormal interactions (or disconnectivity) between different brain regions. While some major deep white matter pathways have been extensively studied (e.g. arcuate fasciculus), studies of short-ranged, “U”-shaped tracts have been limited in patients with schizophrenia, in part due to the sheer abundance of tracts present and due to the spatial variations across individuals that defy probabilistic characterization in the absence of reliable templates. In this study, we use diffusion magnetic resonance imaging (dMRI) to investigate frontal lobe superficial white matter that are present in the majority of study participants, comparing healthy controls and minimally treated patients with first-episode schizophrenia (

Cognitive impairments in schizophrenia are well-documented, present across several cognitive domains and found to be relatively stable over time. However, there is a high degree of heterogeneity and indications of domain-specific developmental courses. The present study investigated the 10-year cognitive course in participants with first-episode schizophrenia (FES) and healthy controls on eight cognitive domains and a composite score, looking at group- and individual-level changes.A total of 75 FES participants and 91 healthy controls underwent cognitive assessment at baseline and follow-up. Linear mixed models were used for group-level analyses and reliable change index (RCI) analyses were used to investigate individual change. The prevalence of clinically significant impairment was explored at both time points, using a cut-off of < −1.5 SD, with significant cognitive impairment defined as impairment on ≥2 domains.Group-level analyses found main effects of group and time, and time by group interactions. Memory, psychomotor processing speed and verbal fluency improved, while learning, mental processing speed and working memory were stable in both groups. FES participants showed deteriorations in attention and cognitive control. Individual-level analyses mainly indicated stability in both FES and controls, except for a higher prevalence of decline in cognitive control in FES. At baseline, 68.8 % of FES participants had clinically significant impairment, compared to 62.3 % at follow-up.We mainly found long-term stability and modest increases in cognition over time in FES, as well as a high degree of within-group heterogeneity. We also found indications of deterioration in participants with worse cognitive performance at baseline.

Background: Early intervention is essential for improving the prognosis in patients with first-episode schizophrenia (FES). The Mental Health Act limits involuntary hospitalization in South Korea to cases where an individual exhibits both a mental disorder and a potential for harming themselves or others, which could result in a delay in the required treatment in FES. We investigated the effect of delay in the first psychiatric hospitalization on clinical outcomes in FES. Methods: The South Korean Health Insurance Review Agency database (2012–2019) was used. We identified 15,994 patients with FES who had a record of at least one psychiatric hospitalization within 1 year from their diagnosis. A multivariate linear regression model and a generalized linear model with a gamma distribution and log link were used to examine associations between the duration from the diagnosis to the first psychiatric admission and clinical outcomes as well as direct medical costs after 2 and 5 years. Results: Within both the 2-year and the 5-year period, longer durations from the diagnosis to the first psychiatric admission were associated with an increase in the number of psychiatric hospitalizations (2-y: B = 0.003, p = 0.003, 5-y: B = 0.007, p = 0.001) and an increase in direct medical costs (total: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.005; inpatient care: 2-y: B = 0.005, p < 0.001, 5-y: B = 0.004, p = 0.017). Conclusions: Earlier psychiatric admission from the diagnosis is associated with a decrease in the number of psychiatric admissions as well as in direct medical costs in patients with FES. [ABSTRACT FROM AUTHOR]

Mentalizing impairment is one of the core features of schizophrenia, and bias judgement of others' gaze as self-directing is common to schizophrenia patients. In this case–control study, 30 patients with first-episode schizophrenia (FES) and 30 matched healthy controls were assigned gaze perception tasks with variable stimulus presentation times (300 ms and no time limit) to determine the presence of self-referential gaze perception (SRGP) bias. The eye movement pattern during the task were tracked and data were analysed using hidden Markov models (HMMs). The SRGP involves reporting of others' gaze intent and was used as a measurement of explicit mentalizing process. Eye movement measurement represents automated visual attention pattern and was considered as a measurement of implicit mentalizing process. The patients with FES had significantly more SRGP bias than the controls in the 300 ms condition but not in the no-time-limit condition. Social cognitive function was related to SRGP bias in the patient group. Two distinct eye movement patterns were identified: eye-focused and nose-focused. Significant group differences in eye movement patterns in the 300 ms condition were found with more controls had eye-focused pattern. Social anxiety symptoms were related to the nose-focused pattern, positive psychotic symptoms were related to the eye-focused pattern, and depressive symptoms were related to less consistent eye movement patterns. No significant relationship was found between SRGP bias and eye movement patterns. The dissociation between explicit and implicit mentalizing processes with different cognitive and symptom dimensions associated with the two processes suggests the presence of different mechanisms. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. Methods: Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups. Results: Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups. Conclusions: PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages. [ABSTRACT FROM AUTHOR]

Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response. However, molecular contributions to response across insular regions remain largely unknown. We used 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to measure glutamate (Glu), Glutamine (Gln), and GABA from anterior and posterior regions of the insula across antipsychotic treatment. A total of 36 participants were examined, including 15 individuals with FES and moderate to severe psychosis who were scanned at two time points, while starting and after 6 weeks of antipsychotic treatment. Symptoms were carefully monitored across the study period to characterize treatment response. GABA, Glu, and Gln levels were calculated relative to creatine in anterior and posterior insular regions, bilaterally. In relation to psychotic symptom reduction, we observed a significant increase in Glu across all insular regions with (p < 0.001), but no corresponding changes in Gln or GABA. In group analyses, the FES cohort showed lower levels of Glu (p < 0.001) and GABA (p = 0.02) at baseline. Finally, in exploratory analyses, treatment remitters demonstrated a normalization of lower insular Glu levels across treatment, unlike non-remitters. Overall, these findings contribute to our understating of molecular changes associated with antipsychotic response and demonstrate abnormalities specific to the insula in FES. [ABSTRACT FROM AUTHOR]