Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

DNA Hyper-methylation Associated With Schizophrenia May Lead to Increased Levels of Autoantibodies.

Background and Hypothesis: Environmental stressors may influence immune surveillance in B lymphocytes and stimulate autoimmune responses via epigenetic DNA methylation modifications in schizophrenia (SCZ). Study Design: A total of 2722, Chinese Han origin subjects were recruited in this study (2005-2011), which included a discovery follow-up cohort with 40 remitters of SCZ (RSCZ), 40 nonremitters of SCZ (NRSCZ), and 40 controls (CTL), and a replication follow-up cohort (64 RSCZ, 16 NRSCZ, and 84 CTL), as well as a case-control validation cohort (1230 SCZ and 1208 CTL). Genomic DNA methylation, target gene mRNA transcripts, and plasma autoantibody levels were measured across cohorts. Study Results: We found extensive differences in global DNA methylation profiles between RSCZ and NRSCZ groups, wherein differential methylation sites (DMS) were enriched with immune cell maturation and activation in the RSCZ group. Out of 2722 participants, the foremost DMS cg14341177 was hyper-methylated in the SCZ group and it inhibited the alternative splicing of its target gene BICD2 and may have increased its autoantigen exposure, leading to an increase in plasma anti-BICD2 IgG antibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in RSCZ endpoint samples but not in NRSCZ endpoint samples. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and positive and negative syndrome scale (PANSS) scores in the RSCZ groups, but not in the NRSCZ groups. Conclusions: These data suggest that abnormal DNA methylation could affect autoreactive responses in SCZ, and that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.

Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Longitudinal changes in cognitive function in early psychosis: a meta-analysis with the MATRICS consensus cognitive battery (MCCB).

INTRODUCTION: A previous meta-analysis indicated stable progress in cognitive functions in early psychosis, assessed through various tools. To avoid assessment-related heterogeneity, this study aims to examine the longitudinal cognitive function changes in early psychosis utilizing the MATRICS Consensus Cognitive Battery (MCCB). METHODS: Embase, PubMed, and Scopus were systematically searched from their inception to September 26th 2023. The inclusion criteria were longitudinal studies that presented follow-up MCCB data for individuals experiencing first-episode psychosis (FEP) and those with ultra-high risk for psychosis (UHR). RESULTS: Twelve studies with 791 participants (566 FEP patients and 225 healthy controls) were subjected to analysis. Suitable UHR studies were absent. Over time, both FEP patients and healthy controls showed significant improvements in MCCB total scores. Furthermore, FEP patients demonstrated improvements across all MCCB domains, while healthy controls only showed augmentations in specific domains such as speed of processing, attention, working memory, and reasoning and problem-solving. Visuospatial learning improvements were significantly greater in FEP patients compared to healthy controls. Subgroup analyses suggested that neither diagnostic type nor follow-up duration influenced the magnitude of cognitive improvement in FEP patients. CONCLUSION: The magnitude of cognitive improvement for MCCB domains was not significantly different between FEP and healthy controls other than visuospatial learning. This underscores visuospatial learning as a potentially sensitive cognitive marker for early pathologic state changes in psychotic disorders.

Disrupted default mode network connectivity in bipolar disorder: a resting-state fMRI study.

BACKGROUND: Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD. METHODS: A total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis. RESULTS: Compared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies. CONCLUSIONS: Our findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia.

BACKGROUND: Cognitive reserve (CR) and the catechol-O-methyltransferase (COMT) Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia. However, the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined. AIM: To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism. METHODS: In a cross-sectional study, 54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype, CR, and negative symptoms. CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale. RESULTS: COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes. In the total sample, significant negative correlations were found between negative symptoms and information, similarities. Associations between information, similarities and negative symptoms were observed in Val homozygotes only, with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms (information, ß = -0.282, 95%CI: -0.552 to -0.011, P = 0.042; similarities, ß = -0.250, 95%CI: -0.495 to -0.004, P = 0.046). CONCLUSION: This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Treatment of antipsychotic-induced hyperprolactinemia: an umbrella review of systematic reviews and meta-analyses.

Background: Hyperprolactinemia is a common antipsychotic-induced adverse event in psychiatric patients, and the quality of clinical studies investigating the best treatments has varied. Thus, to better summarize the clinical evidence, we performed an umbrella review of overlapping systematic reviews and meta-analyses for the treatment of antipsychotic-induced hyperprolactinemia. Methods: The PubMed, Cochrane Library, PsycINFO, Scopus and EMBASE were searched, and reviews and meta-analyses meeting our inclusion criteria were selected. Relevant data were extracted, and an umbrella review was conducted of all included meta-analyses. The quality of included meta-analyses was assessed by using PRISMA scores and AMSTAR 2 quality evaluation. Finally, the clinical evidence for appropriate treatments was summarized and discussed. Results: Five meta-analyses published between 2013 and 2020 met the requirements for inclusion in this umbrella review. The PRISMA scores of the included meta-analyses ranged from 19.5-26. AMSTAR 2 quality evaluation showed that 2 of the 5 included meta-analyses were of low quality and 3 were of very low quality. The included meta-analyses provide clinical evidence that adding aripiprazole or a dopamine agonist can effectively and safely improve antipsychotic-induced hyperprolactinemia. Two meta-analyses also showed that adjunctive metformin can reduce serum prolactin level, but more clinical trials are needed to confirm this finding. Conclusion: Adjunctive dopamine agonists have been proven to be effective and safe for the treatment of antipsychotic-induced hyperprolactinemia. Among the researched treatments, adding aripiprazole may be the most appropriate.

Independent effects of early life adversity on social cognitive function in patients with schizophrenia.

Objective: The aim of this study was to investigate the impact of early life adversity on cognitive function in patients with schizophrenia, with a focus on social cognition (SC). Methods: Two groups of patients with schizophrenia were recruited and matched on sociodemographic and clinical characteristics. One group consisted of 32 patients with a history of childhood trauma (SCZ-ct), and the other group consisted of 30 patients without a history of childhood trauma (SCZ-nct). In addition, 39 healthy controls without a history of childhood trauma (HC-nct) were also recruited. The intelligence of the three groups was assessed using the Wechsler Abbreviated Scale of Intelligence (WAIS-RC) short version. The cognitive function evaluation was conducted using the MATRICS Consensus Cognitive Battery (MCCB), and early life adversity was measured using the Childhood Trauma Questionnaire-Short Form (CTQ) and Bullying Scale for Adults (BSA). Results: Patients with schizophrenia endosed significantly higher scores on the CTQ (F=67.61, p<0.001) and BSA (F=9.84, p<0.001) compared to the HC-nct. Analysis of covariance (ANCOVA) and post-hoc analyses revealed that SCZ-ct (F=11.20, p<0.001) exhibited the most pronounced cognitive impairment among the three groups, as indicated in MCCB total scores and in the domain score of SC. CTQ exhibited a negative correlation with MCCB (r=-0.405, p< 0.001); SC was negatively correlated with physical abuse (PA) of CTQ (r=-0.271, p=0.030) and emotional abuse (EA) of BSA (r=-0.265, p=0.034) in the whole patient sample. Higher SC performance was significantly predicted by CT_total (Beta =-0.582, p<0.001, 95% CI -0.96-0.46), and years of education (Beta=0.260, p =0.014, 95% CI 0.20-1.75) in schizophrenia. Conclusions: Besides familial trauma, schizophrenia patients appear to have a higher likelihood of experiencing bullying in their early life. These experiences seem to contribute significantly to their severe impairments in SC.

Comparative Analysis of Personality Traits in Major Depressive Disorder and Bipolar Disorder: Impact, Differences, and Associations with Symptoms.

Purpose: This cross-sectional study aimed to compare the personality traits of patients with major depressive disorder (MDD) and bipolar disorder (BD) with those of healthy individuals. The goal was to gain insight into the potential impact of personality traits on the development and manifestation of mood disorders. Methods: One hundred seventy-eight patients with mood disorders were analyzed as either MDD or BD, with each group containing euthymic and depressive members: e-MDD, d-MDD, e-BD, and d-BD. Mood status was assessed using the Young Mania Rating Scale (YMRS), and the 17-item Hamilton Depression Rating Scale (HAMD-17). Ninety-five healthy individuals served as controls. Personality traits were assessed with the Eysenck Personality Questionnaire. Results: The scores for neuroticism in the patient groups were comparable, but each group had higher scores compared to the control group (P < 0.001). Each patient group exhibited significantly lower scores for extraversion compared to the control group, with e-MDD, d-MDD, and d-BD showing particularly notable differences (P < 0.001); these groups scored significantly lower than the e-BD (P = 0.041, 0.009, 0.038). In patients with BD, there was an inverted association between extraversion score and HAMD total score (P = 0.010, r = -0.27), and a positive association with the YMRS total score (P = 0.022, r = 0.24). In the MDD group, there was a positive association between the neuroticism score and HAMD total score (P = 0.021, r = 0.25). Conclusion: Patients with mood disorders are characterized by lower extraversion and higher neuroticism. Level of neuroticism associated with depression severity in MDD. Patients with BD may be more extraverted, but their extraversion can be affected by depressive episodes. Extraversion may be a feature of BD, and may differentiate BD from MDD. Personality traits are related to disease diathesis and state, and shaped by symptom manifestations.

Decreased dynamic variability of the cerebellum in the euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a complex mental illness characterized by different mood states, including depression, mania/hypomania, and euthymia. This study aimed to comprehensively evaluate dynamic changes in intrinsic brain activity by using dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic degree centrality (dDC) in patients with BD euthymia or depression and healthy individuals. METHODS: The resting-state functional magnetic resonance imaging data were analyzed from 37 euthymic and 28 depressed patients with BD, as well as 85 healthy individuals. Using the sliding-window method, the dfALFF and dDC were calculated for each participant. These values were compared between the 3 groups using one-way analysis of variance (ANOVA). Additional analyses were conducted using different window lengths, step width, and window type to ensure the reliability of the results. RESULTS: The euthymic group showed significantly lower dfALFF and dDC values of the left and right cerebellum posterior lobe compared with the depressed and control groups (cluster level PFWE < 0.05), while the latter two groups were comparable. Brain regions showing significant group differences in the dfALFF analysis overlapped with those with significant differences in the dDC analysis. These results were consistent across different window lengths, step width, and window type. CONCLUSIONS: These findings suggested that patients with euthymic BD exhibit less flexibility of temporal functional activities in the cerebellum posterior lobes compared to either depressed patients or healthy individuals. These results could contribute to the development of neuropathological models of BD, ultimately leading to improved diagnosis and treatment of this complex illness.

Different levels of prepulse inhibition among patients with first-episode schizophrenia, bipolar disorder and major depressive disorder.

BACKGROUND: Deficits in prepulse inhibition may be a common feature in first-episode schizophrenia, bipolar disorder (BD) and major depressive disorder (MDD). We sought to explore the levels and viability of prepulse inhibition to differentiate first-episode schizophrenia, BD and MDD in patient populations. METHODS: We tested patients with first-episode schizophrenia, BD or MDD and healthy controls using prepulse inhibition paradigms, namely perceived spatial co-location (PSC-PPI) and perceived spatial separation (PSS-PPI). RESULTS: We included 53 patients with first-episode schizophrenia, 30 with BD and 25 with MDD, as well as 82 healthy controls. The PSS-PPI indicated that the levels of prepulse inhibition were smallest to largest, respectively, in the first-episode schizophrenia, BD, MDD and control groups. Relative to the healthy controls, the prepulse inhibition deficits in the first-episode schizophrenia group were significant (p < 0.001), but the prepulse inhibitions were similar between patients with BD and healthy controls, and between patients with MDD and healthy controls. The receiver operating characteristic curve analysis showed that PSS-PPI (area under the curve [AUC] 0.73, p < 0.001) and latency (AUC 0.72, p < 0.001) were significant for differentiating patients with first-episode schizophrenia or BD from healthy controls. LIMITATIONS: The demographics of the 4 groups were not ideally matched. We did not perform cognitive assessments. The possible confounding effect of medications on prepulse inhibition could not be eliminated. CONCLUSION: The level of prepulse inhibition among patients with first-episode schizophrenia was the lowest, with levels among patients with BD, patients with MDD and healthy controls increasingly higher. The PSS-PPI paradigm was more effective than PSC-PPI to recognize deficits in prepulse inhibition. These results provide a basis for further research on biological indicators that can assist differential diagnoses in psychosis.

Trajectories of social function in patients with first-episode schizophrenia: Analysis of data from a 10-year follow-up study.

BACKGROUND: Patients with schizophrenia may have diverse functional outcomes. However, the long-term functional trajectories of patients with first-episode schizophrenia (FES) are unclear. METHODS: We extracted data from the Chinese First-Episode Schizophrenia Trial, a 10-year prospective study of antipsychotic-naïve patients with FES. We applied K means cluster modelling to longitudinal data on the social function of patients with FES and examined associations of the empirically derived trajectories with baseline clinical characteristics of the 10-year follow-up. OUTCOMES: Three distinct functional trajectories emerged: improving-favorable (39·3%), improving-poor (17·8%) and improving-stable (42·9%). All three trajectories demonstrated Personal and Social Performance (PSP) score improvement in the first six months. The improving-poor trajectory demonstrated PSP score decline during the second six months and thereafter, while PSP scores in the other two trajectories were mainly stable during the same period. Patients in the improving-favorable trajectory had higher baseline PSP scores than those in the improving-poor trajectory (OR=0·904 [0·852, 0·961], p < 0·05) and the improving-stable trajectory (OR=0·870 [0·825, 0·918], p < 0·001) and were more likely to be female than those in the improving-stable trajectory (OR=2·699 [1·030, 7·074], p < 0·05). CONCLUSIONS: Patients with FES demonstrated varied long-term functional recovery profiles. The first year, especially the second half of the first year, is a key period for social function interventions that improve long-term functional outcomes. Male patients and patients with poor baseline function may particularly benefit from such interventions.

The Role of Total White Blood Cell Count in Antipsychotic Treatment for Patients with Schizophrenia.

BACKGROUND: Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study. METHODS: Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response. RESULTS: At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly (p < 0.05). Lower baseline TWBCc predicted greater reductions in Positive and Negative Syndrome Scale (PANSS) total and negative scores over time (p < 0.05). We found significant mediation of TWBCc for effects of waist circumference, fasting low-density lipoprotein cholesterol, and glucose on reductions in PANSS total scores and PANSS negative subscale scores (p < 0.05). CONCLUSION: TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.

Cognitive deficits profiles in the first-episode of schizophrenia, clinical high risk of psychosis, and genetically high-risk of psychosis.

Background: Cognitive deficits are core characteristics of schizophrenia, presenting before the emergence of psychotic symptoms. Individuals with a clinical high-risk for psychosis (CHR) and those with genetically high-risk of psychosis (GHR) also exhibit cognitive impairments. Nonetheless, it remains uncertain in which domains of cognitive impairments in these two groups were more similar to those of schizophrenia patients. Moreover, it is unclear which domains of impairment are caused by quality factors and which are more related to the state of disease. This research initiative aimed to extensively examine the distinct cognitive impairment profiles among the CHR, GHR, and first-episode schizophrenia (FES) cohorts. Methods: We compared the cognitive functions of the three groups and a healthy control group (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). The participants for this study were recruited from the Beijing Anding Hospital of Capital Medical University. Our sample consisted of 56 patients with FES, 42 with CHR, 26 with GHR, and 62 HCs. The participants across all groups were matched in terms of gender, age, and level of education. Results: Individuals with FES, GHR, and CHR showed significant impairment across the majority of MCCB domains, with the exception of visual learning, in comparison to HCs. None of the MCCB domains demonstrated a discerning ability to accurately differentiate between individuals with CHR and those with GHR. In the speed of processing and attention/vigilance domains, individuals with GHR and CHR exhibited scores between those of FES and HCs, with all group differences reaching statistical significance. This pattern of results indicates an intermediate level of cognitive function in individuals with GHR and CHR. Conversely, the levels of impairment observed in working memory and verbal learning were relatively consistent across all three groups: FES, CHR, and GHR. Notably, individuals in the CHR group exhibited performance akin to that of the HCs in the reasoning/problem-solving domain, while showing significant differences from the FES group, with the CHR individuals demonstrating better performance. Additionally, individuals with GHR displayed performance in social cognition similar to that of the HCs, while also demonstrating significant distinctions from the FES group, with the GHR individuals demonstrating better performance. Conclusion: Significant cognitive deficits exist in individuals with CHR, GHR, and FES, and these deficits vary across domains. Processing speed and attention/vigilance could potentially serve as robust biomarkers for identifying individuals at a risk of psychosis. The impairment observed in reasoning/problem-solving abilities might signify a qualitative trait, whereas deficits in social recognition could indicate a state characteristic specific to schizophrenia.

Quality of life and its predictors in first-episode schizophrenia and individuals at clinical high-risk for psychosis.

BACKGROUND: This is a cross-sectional study comparing the degree of subjective quality of life (QOL) impairment and its predictive factors in first-episode schizophrenia (FES) and individuals at clinical high-risk (CHR) for psychosis. METHODS: Seventy-seven FES, 59 CHR, and 64 healthy controls (HC) were included. The QOL of all participants was assessed using the World Health Organization Quality of Life (WHOQOL)-Brief Form (BREF). Psychiatric symptoms of individuals with FES were assessed with the Positive and Negative Syndrome Scale (PANSS), five factors were further identified through factor analysis; for individuals with CHR and HC, the Scale of Prodromal Symptoms (SOPS) was used. RESULTS: The total and four sub-domain scores of the WHOQOL-BREF in the FES and CHR groups were lower than those of the HC group. The overall and psychological health scores in the CHR group were lowest. In the FES group, after applying Bonferroni's correction, there is a negative correlation between the total QOL scores and anxiety/depressive symptom scores (r = -0.34, P = 0.003). The stepwise multiple regression analysis showed that the QOL of both FES and CHR group were negatively affected by anxiety/depressive symptoms and unemployment (P < 0.05). CONCLUSIONS: Compared with FES, CHR individuals are more dissatisfied with their QOL. Although diagnostic assessment of FES and CHR relies heavily on positive symptoms, the QOL is more affected by anxiety/depressive symptoms and social functioning.

Core of sensory gating deficits in first-episode schizophrenia: attention dysfunction.

Background: Sensory gating deficits are a common feature of schizophrenia and may be indicative of higher-order psychopathological impairments. It has been proposed that incorporating subjective attention components into prepulse inhibition (PPI) measures may improve the accuracy of assessing these deficits. This study aimed to investigate the relationship between modified PPI and cognitive function, with a specific focus on subjective attention, to gain a better understanding of the underlying mechanisms of sensory processing deficits in schizophrenia. Methods: Fifty-four unmedicated first-episode schizophrenia (UMFE) patients and 53 healthy controls participated in this study. The modified Prepulse Inhibition paradigm, including Perceived Spatial Separation PPI (PSSPPI) and Perceived Spatial Colocation PPI (PSCPPI), was used to evaluate sensorimotor gating deficits. Cognitive function was assessed in all participants using the Chinese version of the MATRICS Consensus Cognitive Suite Test (MCCB). Results: UMFE patients had lower MCCB scores and deficient PSSPPI scores than healthy controls. PSSPPI was negatively correlated with total PANSS scores and positively correlated with the speed of processing, attention/ vigilance, and social cognition. Multiple linear regression analysis showed that the PSSPPI at 60 ms had a significant effect on attentional/ vigilance and social cognition, even after controlling for gender, age, years of education, and smoking. Conclusion: The study revealed notable impairments in sensory gating and cognitive function in UMFE patients, best reflected by the PSSPPI measure. Specifically, PSSPPI at 60 ms was significantly associated with both clinical symptoms and cognitive performance, suggesting that PSSPPI at 60 ms may capture psychopathological symptoms related to psychosis.

A brief history of clozapine in China with a look forward.

Clozapine was first manufactured in China in 1976. Clozapine is currently used not only for treatment-refractory schizophrenia (TRS), but also continues to be used in the treatment of patients with non-TRS and other mental disorders; moreover, low-dose clozapine is also used in sedative-hypnotic therapy and in combination with other drugs. There is need for studies in China using various titrations and assessing their risk for myocarditis and aspiration pneumonia. The Chinese clozapine package insert will also greatly benefit from these changes.

The deficient cue monitoring and the facilitating effect of prosocial intention on prospective memory in patients with schizophrenia spectrum disorders.

The study aimed to investigate the cognitive processing of prospective memory (PM) in patients with schizophrenia spectrum disorders (SSDs) by using an eye-tracking paradigm. In addition, the facilitating effects of prosocial intention (the desire to help others) on PM in SSDs were also examined. In phase 1, 26 patients (group1) and 25 healthy controls (HCs) were compared in an eye-tracking PM paradigm in terms of the PM accuracy and eye-tracking indices. In phase 2, 21 more patients (group2) were recruited, and a prosocial intention was introduced in the eye-tracking PM paradigm. Their PM accuracy and eye-tracking indices were compared with those in group1. The PM cue monitoring was indicated by the total fixation counts and fixation time on distractor words. In phase 1, group1 showed lower PM accuracy, fewer fixation counts and less fixation time on distractor words than HCs. In phase 2, group2 (with prosocial intention) performed significantly better than group1 (with typical instruction) on both PM accuracy and fixation time on distractor words. In both groups of SSDs, the PM accuracy was significantly correlated with both the fixation counts and the fixation time of distractor words. After controlling for the cue monitoring indices, the difference in PM accuracy remained significant between group1 and HCs but disappeared between group1 and group2. The cue monitoring deficit contributes to the PM impairment in SSDs. The facilitating effect of prosocial intention disappears after the control of cue monitoring, also indicating its critical role in PM.

Erythrocyte Membrane Fatty Acid Composition as a Potential Biomarker for Depression.

BACKGROUND: Major depressive disorders is a chronic and severe psychiatric disorder with poor prognosis and quality of life. Abnormal erythrocyte fatty acid (FA) composition in depressed patients were found in our previous study, but the relationship between erythrocyte membrane FA levels and different severity of depressive and anxiety symptoms remains to be explored. METHODS: This cross-sectional study included 139 patients with first-diagnosed, drug-naïve depression and 55 healthy controls whose erythrocyte FA composition was analyzed. Patients with depression were divided into severe depression and mild to moderate depression or depression with severe anxiety and mild to moderate anxiety. Then the differences of FA levels among different groups were analyzed. Finally, the receiver operating characteristic curve analysis was applied to identify potential biomarkers in distinguishing the severity of depressive symptoms. RESULTS: Levels of erythrocyte membrane FAs were elevated among patients with severe depression compared with healthy controls or patients with mild to moderate depression of almost all kinds. While C18:1n9t (elaidic acid), C20:3n6 (eicosatrienoic acid), C20:4n6 (arachidonic acid), C22:5n3 (docosapentaenoic acid), total fatty acids (FAs), and total monounsaturated FAs were elevated in patients with severe anxiety compared with patients with mild to moderate anxiety. Furthermore, the level of arachidonic acid, C22:4n6 (docosatetraenoic acid), elaidic acid, and the combination of all 3 were associated with the severity of depressive symptoms. CONCLUSIONS: The results suggested that erythrocyte membrane FA levels have the potential to be the biological indicator of clinical characteristics for depression, such as depressive symptoms and anxiety. In the future, more research is needed to explore the causal association between FA metabolism and depression.