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Anhedonia is one of the core features of the negative symptoms of schizophrenia and can be extremely burdensome. Our study applied resting-state functional magnetic resonance imaging (fMRI)-based support vector regression (SVR) to predict anhedonia in patients with first-episode schizophrenia (FES) and analysed the correlation between the wavelet-based amplitude low-frequency fluctuation (wavelet-ALFF) of the main brain region and anhedonia. We recruited 31 patients with FES and 33 healthy controls (HCs) from the Affiliated Brain Hospital of Guangzhou Medical University. All subjects completed the Temporal Experience of Pleasure Scale (TEPS) and received resting-state fMRI (rs-fMRI). We used the wavelet-ALFF method and SVR to analyse the data. Patients with FES had lower consummatory pleasure scores than healthy subjects (t = -2.71, P<0.01). FES displays variable wavelet-ALFF in a wide range of cerebral cortices (P<0.05, GFR corrected). The SVR analysis showed that wavelet-ALFF, based primarily on the right putamen (r = 0.40, P<0.05) and right superior occipital gyrus (r = -0.39, P<0.05), was effective in predicting consummatory pleasure scores with an accuracy of 56.43 %. Our study shows that abnormal spontaneous neural activity in FES may be related to the state of consummatory anhedonia in FES. Wavelet-ALFF changes in the right putamen and superior occipital gyrus may be a biological feature of FES with anhedonia and could serve as a potential biological marker of FES with anhedonia., (Copyright © 2024 The Affiliated Brain Hospital, Guangzhou Medical University. Published by Elsevier Inc. All rights reserved.)

Background: A growing body of evidence supports the comorbidity between depression (DEP) and obesity, yet the genetic mechanisms underlying this association remain unclear. Our study explored the shared genetic architecture and causal associations of DEP with BMI., Methods: We investigated the multigene overlap and genetic correlation between DEP (N > 1.3 million) and BMI (N = 806,834) based on genome-wide association studies (GWAS) and using the bivariate causal mixture model and linkage disequilibrium score regression (LDSC). The causal association was explored by bi-directional Mendelian randomization (MR). Common risk loci were identified through cross-trait meta-analyses. Stratified LDSC and multi-marker gene annotation analyses were applied to investigate single-nucleotide polymorphisms enrichment across tissue types, cell types, and functional categories. Finally, we explored shared functional genes by Summary Data-Based Mendelian Randomization (SMR) and further detected differential expression genes (DEG) in brain tissues of individuals with depression and obesity., Results: We found a positive genetic correlation between DEP and BMI (r g = 0.19, P = 4.07 × 10 -26 ), which was more evident in local genomic regions. Cross-trait meta-analyses identified 16 shared genetic loci, 5 of which were newly identified, and they had influence on both diseases in the same direction. MR analysis showed a bidirectional causal association between DEP and BMI, with comparable effect sizes estimated in both directions. Combined with gene expression information, we found that genetic correlations between DEP and BMI were enriched in 6 brain regions, predominantly in the nucleus accumbens and anterior cingulate cortex. Moreover, 6 specific cell types and 23 functional genes were found to have an impact on both DEP and BMI across the brain regions. Of which, NEGR1 was identified as the most significant functional gene and associated with DEP and BMI at the genome-wide significance level (P < 5 × 10 -8 ). Compared with healthy controls, the expression levels of NEGR1 gene were significant lower in brain tissues of individuals with depression and obesity., Conclusions: Our study reveals shared genetic basis underpinnings between DEP and BMI, including genetic correlations and common genes. These insights offer novel opportunities and avenues for future research into their comorbidities., (© 2024. The Author(s).)

Background: Deficits in speech and emotion perception are intertwined with psychiatric symptoms. How the happy prosody embedded in speech affects target speech-in-noise recognition (TSR) and relates to psychiatric symptoms in patients with schizophrenia (SCHs) remains unclear. This study examined spontaneous brain activity underlying happy TSR and its association with psychiatric symptom dimensions in SCHs., Methods: Fifty-four SCHs and 59 healthy control participants (HCs) underwent the TSR task, Positive and Negative Syndrome Scale (PANSS) assessment, and magnetic resonance imaging scanning. Multivariate analyses of partial least squares (PLS) regression were used to explore the associations between whole-brain fractional amplitude of low-frequency fluctuations (fALFF), happy-neutral TSR (target pseudo-sentences were uttered in happy and neutral prosodies), and five PANSS factor scores (excitement/hostility, depression/anxiety, cognition, positive, and negative)., Results: The happy prosody did not alter TSR or TSR changing rates in either SCHs or HCs. SCHs exhibited lower happy and neutral TSR than HCs. A fALFF PLS component (including precentral/postcentral gyrus, Subcallosal Cortex, several temporal regions, and cerebellum) was associated with happy and neutral TSR. SCHs demonstrated higher PLS fALFF scores and PLS TSR scores than HCs. In SCHs, PLS fALFF scores were correlated with the PANSS positive factor score, and PLS TSR scores were correlated with the PANSS cognition factor score., Conclusions: The positive-psychiatric-symptoms-related spontaneous activity profile was associated with happy and neutral TSR, contributing to the cognition psychiatric symptoms dimension. The findings suggest the potential to improve positive and cognitive symptoms by enhancing happy and neutral TSR in schizophrenia based on neuroplasticity., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To identify the risk and protective factors affecting thirst symptoms in patients with heart failure (HF) and intervention strategies to alleviate thirst symptoms., Design: An integrative review., Methods: A total of 61 articles were retrieved. Screening yielded a total of 21 articles which were appraised for quality. The quality of studies was assessed using the Mixed Methods Appraisal Tool., Data Sources: Ten electronic databases were searched in October 2023, including Embase, Pubmed, CINAHL, Cochrane, Web of Science, Wiley, CNKI, VIP, CBM and WanFang. In addition, we searched grey databases and manually searched reference lists of included and relevant reviews., Results: In total, 1644 articles were retrieved, of which 21 were included. Eight studies addressed the factors. Six themes emerged as risk factors, including demographics, severity of disease, psycho-environmental, medication, fluid restriction and homeostasis. Conversely, an increase in fluid intake, a high score of sodium restriction diet attitude and using ARB were identified as protective factors. Thirteen studies focus on intervention strategies. Five unique intervention strategies were identified, including Traditional Chinese Medicine, mint-related interventions, sour-flavour interventions, improved water restriction and cluster nursing strategy., Conclusion: This finding identified the factors associated with thirst symptoms in patients with HF, especially concerning the elaboration of risk factors, which suggests that healthcare professionals should focus on the risk factors for thirst in patients with HF and consciously avoid the occurrence of these risk factors. Additionally, there are considerable cultural differences in interventions, therefore, to increase adherence during symptom management, careful selection of appropriate intervention strategies based on the requirements and preferences of patients is required. While there are some therapies, there aren't enough high-quality empirical investigations. Thus, multi-centre, large-sample studies are also required in subsequent research to demonstrate the interventions' effectiveness., Implications for the Profession: The nurse must notice the symptoms of thirst in HF to slow down the disease's progression and improve the patient's physical and emotional well-being., Reporting Method: The review complies with the PRISMA guidelines for reporting systematic reviews., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Background: Abnormal functional connectivity (FC) in the brain has been observed in schizophrenia patients. However, studies on FC between homotopic brain regions are limited, and the results of these studies are inconsistent. The aim of this study was to compare homotopic connectivity between first-episode schizophrenia (FES) patients and healthy subjects and assess its correlation with clinical symptoms., Methods: Thirty-one FES patients and thirty-three healthy controls (HC) were included in the study. The voxel-mirrored homotopic connectivity (VMHC) method of resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyse the changes in homotopic connectivity between the two groups. The 5-factor PANSS model was used to quantitatively evaluate the severity of symptoms in FES patients. Partial correlation analysis was used to assess the correlation between homotopic connectivity changes and clinical symptoms., Results: Compared to those in the HC group, VMHC values were decreased in the paracentral lobule (PL), thalamus, and superior temporal gyrus (STG) in the FES group (P < 0.05, FDR correction). No significant differences in white matter volume (WMV) within the subregion of the corpus callosum or in brain regions associated with reduced VMHC were observed between the two groups. Partial correlation analyses revealed that VMHC in the bilateral STG of FES patients was positively correlated with negative symptoms (r left  = 0.46, p < 0.05; r right  = 0.47, p < 0.05), and VMHC in the right thalamus was negatively correlated with disorganized/concrete symptoms (r right  = 0.45, p < 0.05)., Conclusion: Our study revealed that homotopic connectivity is altered in the resting-state brain of FES patients and correlates with the severity of negative symptoms; this change may be independent of structural changes in white matter. These findings may contribute to the development of the abnormal connectivity hypothesis in schizophrenia patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China., Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m 2 was considered obese, and BMI < 25 kg/m 2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University., Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients., Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yi et al.)

Background: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia., Methods: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively., Results: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%)., Conclusions: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks., Trial Registration: This study was registered on Clinicaltrials.gov (NCT03451734)., (© 2023. The Author(s).)

Background: Patients with schizophrenia (SCH) have deficits in source monitoring (SM), speech-in-noise recognition (SR), and auditory prosody recognition. This study aimed to test the covariation between SM and SR alteration induced by negative prosodies and their association with psychiatric symptoms in SCH., Methods: Fifty-four SCH patients and 59 healthy controls (HCs) underwent a speech SM task, an SR task, and the assessment of positive and negative syndrome scale (PANSS). We used the multivariate analyses of partial least squares (PLS) regression to explore the associations among SM (external/internal/new attribution error [AE] and response bias [RB]), SR alteration/release induced by four negative-emotion (sad, angry, fear, and disgust) prosodies of target speech, and psychiatric symptoms., Results: In SCH, but not HCs, a profile (linear combination) of SM (especially the external-source RB) was positively associated with a profile of SR reductions (induced especially by the angry prosody). Moreover, two SR reduction profiles (especially in the anger and sadness conditions) were related to two profiles of psychiatric symptoms (negative symptoms, lack of insight, and emotional disturbances). The two PLS components explained 50.4% of the total variances of the release-symptom association., Conclusion: Compared to HCs, SCH is more likely to perceive the external-source speech as internal/new source speech. The SM-related SR reduction induced by the angry prosody was mainly associated with negative symptoms. These findings help understand the psychopathology of SCH and may provide a potential direction to improve negative symptoms via minimizing emotional SR reduction in schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

It was still unclear that the correlation between the resting-state intrinsic activity in brain regions and facial emotion recognition (FER) ability in patients with first-episode schizophrenia (FSZ). Our aim was to analyse the correlation between the fractional amplitude of low-frequency fluctuation (fALFF) and FER ability in FSZ patients. A total of 28 patients with FSZ and 33 healthy controls (HCs) completed visual search tasks for FER ability. Regions of interest (ROIs) related to facial emotion were obtained from a previous meta-analysis. Pearson correlation analysis was performed to understand the correlation between fALFF and FER ability. Our results indicated that the patients performed worse than the HCs in the accuracy performances of happy FER and fearful FER. The previous meta-analysis results showed that the brain regions related to FER included the bilateral amygdala (AMY)/hippocampus (HIP), right fusiform gyrus (FFG), and right supplementary motor area (SMA). Partial correlation analysis showed that the fALFF of the right FFG was associated with high-load fearful FER accuracy (r = - 0.60, p = 0.004). Our study indicated that FER ability is correlated with resting-state intrinsic activity in brain regions related to facial emotion, which may provide a reference for the study of FER deficiency in schizophrenia., (© 2022. The Author(s).)

Objective: This study aims to identify the functional heterogeneity in fully or partially remitted patients with bipolar disorder and explore the correlations between psychosocial functioning and sociodemographic, clinical, neurocognitive and biochemical variables., Methods: One hundred and forty fully or partially remitted patients with bipolar disorder ( BD ) and seventy healthy controls were recruited. The patients were grouped into different profiles based on the Functioning Assessment Short Test ( FAST ) domain scores by hierarchical cluster analysis. The characteristics of subgroups and the correlations between psychosocial functioning and sociodemographic, clinical, neurocognitive and biochemical variables in each cluster were then analyzed., Results: There were three subgroups in fully or partially remitted patients with BD: the lower functioning group (LF ), performed global functioning impairments; the moderate functioning group ( MF ), presented selective impairments in functional domains; and the good functioning subgroup ( GF ), performed almost intact functioning. Among the three subgroups, there were differences in FAST domains, sociodemographic variables, clinical variables, some neurocognitive domains and several biochemical indexes., Conclusions: The study successfully identified three functional subgroups. The characteristics of discrete subgroups and the specific clinical factors, neurocognitive domains and biochemical indexes that are correlated with functional subgroups will allow for making tailored interventions to promote functional recovery and improve the quality of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ba, Chen, Lai, Liao, Fang, Lu, Zheng, Zong and Lin.)

Object: Despite abundant literature demonstrating a high prevalence of obesity and overweight in people with bipolar disorder (BD), little is known about this topic in China. Therefore, we assessed the prevalence and associated factors of obesity and overweight among inpatients with BD in our hospital, one of the largest public psychiatric hospitals in China., Methods: In this retrospective, cross-sectional study, 1,169 inpatients ≥18 years with BD during 2019 were included. Obesity was defined as having a BMI ≥25 kg/m 2 , and overweight was defined as having a BMI from 23 kg/m 2 to <25 kg/m 2 . Binary logistic regression analysis was performed to identify factors associated with obesity and overweight., Results: The prevalence of obesity and overweight was 21.0% and 32.2% in patients with BD, respectively. Compared to patients with overweight and normal weight, patients with obesity were older, had a longer duration of BD and a longer length of hospital stay, had a higher prevalence of diabetes and hypertension, and had a higher level of all metabolic indices, except for HDL cholesterol. Binary logistic regression analysis showed that duration of BD, uric acid, alanine aminotransferase (ALT), triglyceride, and LDL cholesterol were significantly associated with obesity, and male sex and uric acid level were significantly associated with overweight ( p < 0.05)., Conclusions: Obesity and overweight were fairly prevalent in Chinese BD patients, and several factors were related to obesity and overweight. The results of the present study call for the need to implement early screening, prevention and interventions for obesity and overweight in patients with BD in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yi, Wu, Li, Li, Song, She and Zheng.)

Objective: Cognitive symptoms are associated with significant dysfunction in schizophrenia. Oxidative stress and inflammation involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. The objective of this study was to determine the efficacy of sulforaphane on cognition dysfunction for patients with schizophrenia., Methods: This double-blind randomized 22-week trial of patients with first-episode schizophrenia was conducted in four psychiatric institutions in China. Patients were randomized to three groups (two doses of sulforaphane vs. placebo) and symptomatic and cognitive assessments were completed at multiple times. The primary outcome measure was change in the MATRICS Composite score. The secondary outcomes were change in MATRICS Domain scores, PANSS Total Scores and change in side-effects., Results: A total of 172 patients were randomized and 151 patients had at least one follow up evaluation. There were no significant effects of sulforaphane, on the primary outcome, MATRICS overall composite score. However, on secondary outcomes, sulforaphane did significantly improve performance scores on MATRICS battery Domains of spatial working memory ( F = 5.68, P = 0.004), reasoning-problem solving ( F = 2.82, P = 0.063), and verbal learning ( F = 3.56, P = 0.031). There were no effects on PANSS symptom scores. Sulforaphane was well tolerated., Conclusion: Although the primary outcome was not significant, improvement in three domains of the MATRICS battery, suggests a positive cognitive effect on some cognitive functions, which warrants further clinical trials to further assess whether sulforaphane may be a useful adjunct for treating some types of cognitive deficits in schizophrenia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Patients with bipolar disorder ( BD ) may experience family dysfunction, which might result in worse psychosocial functioning through environmental and psychological factors. Research investigating the mediating role of social support, resilience and suicidal ideation on family and psychosocial functioning in BD is rare. The study aims to explore the predicting and mediating effects of social support, resilience and suicidal ideation on family and psychosocial functioning in BD patients. Two hundred forty-six patients with BD and sixty-nine healthy controls were recruited. The Family Assessment Device ( FAD ), Functioning Assessment Short Test ( FAST ), Social Support Rating Scale ( SSRS ), Connor-Davidson Resilience Scale ( CD-RISC ) and Beck Scale for Suicide Ideation ( BSI ) were used to assess family functioning, psychosocial functioning, social support, resilience and suicidal ideation, respectively. Bipolar patients exhibited worse family and psychosocial functioning than healthy controls. Family functioning, social support, resilience and suicidal ideation significantly predict psychosocial functioning in the bipolar group. Social support, resilience and suicidal ideation indirectly mediate the effect of family functioning on psychosocial functioning in bipolar patients. Cross-sectional design and mixed sample including acute and remitted stages. Treatments for patients with bipolar disorder should be combined with family strategies that are formulated to improve psychosocial functioning. An emphasis should be placed on enhancing social support and resilience while paying attention to suicidal ideation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dou, Yu, Fang, Lu, Cai, Zhu, Zong, Zheng and Lin.)

Schizophrenia is a chronic disorder characterized by specific positive and negative primary symptoms, social behavior disturbances and cognitive deficits (e.g., impairment in working memory and cognitive flexibility). Mounting evidence suggests that altered excitability and inhibition at the molecular, cellular, circuit and network level might be the basis for the pathophysiology of neurodevelopmental and neuropsychiatric disorders such as schizophrenia. In the past decades, human and animal studies have identified that glutamate and gamma-aminobutyric acid (GABA) neurotransmissions are critically involved in several cognitive progresses, including learning and memory. The purpose of this review is, by analyzing emerging findings relating to the balance of excitatory and inhibitory, ranging from animal models of schizophrenia to clinical studies in patients with early onset, first-episode or chronic schizophrenia, to discuss how the excitatory-inhibitory imbalance may relate to the pathophysiology of disease phenotypes such as cognitive deficits and negative symptoms, and highlight directions for appropriate therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Ouyang, Zheng, Mi, Zhao, Ning and Guo.)

Detection of transient changes in interaural correlation is based on the temporal precision of the central representations of acoustic signals. Whether schizophrenia impairs the temporal precision in the interaural correlation process is not clear. In both participants with schizophrenia and matched healthy-control participants, this study examined the detection of a break in interaural correlation (BIC, a change in interaural correlation from 1 to 0 and back to 1), including the longest interaural delay at which a BIC was just audible, representing the temporal extent of the primitive auditory memory (PAM). Moreover, BIC-induced electroencephalograms (EEGs) and the relationships between the early binaural psychoacoustic processing and higher cognitive functions, which were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), were examined. The results showed that compared to healthy controls, participants with schizophrenia exhibited poorer BIC detection, PAM and RBANS score. Both the BIC-detection accuracy and the PAM extent were correlated with the RBANS score. Moreover, participants with schizophrenia showed weaker BIC-induced N1-P2 amplitude which was correlated with both theta-band power and inter-trial phase coherence. These results suggested that schizophrenia impairs the temporal precision of the central representations of acoustic signals, affecting both interaural correlation processing and higher-order cognitions., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Impaired face perception is considered as a hallmark of social disability in schizophrenia. It is widely believed that inverted faces and upright faces are processed by distinct mechanisms. Previous studies have identified that individuals with schizophrenia display poorer face processing than controls. However, the mechanisms underlying the face inversion effect (FIE) in patients with first-episode schizophrenia (FSZ) remain unclear., Methods: We designed an fMRI task to investigate the FIE mechanism in patients with schizophrenia. Thirty-four patients with FSZ and thirty-five healthy controls (CON) underwent task-related fMRI scanning, clinical assessment, anhedonia experience examination, and social function and cognitive function evaluation., Results: The patients with FSZ exhibited distinct functional activity regarding upright and inverted face processing within the cortical face and non-face network. These results suggest that the differences in quantitative processing might mediate the FIE in schizophrenia. Compared with controls, affected patients showed impairments in processing both upright and inverted faces; and for these patients with FSZ, upright face processing was associated with more severe and broader impairment than inverted face processing. Reduced response in the left middle occipital gyrus for upright face processing was related to poorer performance of social function outcomes evaluated using the Personal and Social Performance Scale., Conclusion: Our data suggested that patients with FSZ exhibited similar performance in processing inverted faces and upright faces, but were less efficient than controls; and for these patients, inverted faces are processed less efficiently than upright faces. We also provided a clue that the mechanism under abnormal FIE might be related to an aberrant activation of non-face-selective areas instead of abnormal activation of face-specific areas in patients with schizophrenia. Finally, our study indicated that the neural pathway for upright recognition might be relevant in determining the functional outcomes of this devastating disorder., Competing Interests: The authors declare no conflicts of interest., (© 2021 Liu et al.)

Background: Development and validation of a deep learning method to automatically segment the peri-ampullary (PA) region in magnetic resonance imaging (MRI) images., Methods: A group of patients with or without periampullary carcinoma (PAC) was included. The PA regions were manually annotated in MRI images by experts. Patients were randomly divided into one training set, one validation set, and one test set. Deep learning methods were developed to automatically segment the PA region in MRI images. The segmentation performance of the methods was compared in the validation set. The model with the highest intersection over union (IoU) was evaluated in the test set., Results: The deep learning algorithm achieved optimal accuracies in the segmentation of the PA regions in both T1 and T2 MRI images. The value of the IoU was 0.68, 0.68, and 0.64 for T1, T2, and combination of T1 and T2 images, respectively., Conclusions: Deep learning algorithm is promising with accuracies of concordance with manual human assessment in segmentation of the PA region in MRI images. This automated non-invasive method helps clinicians to identify and locate the PA region using preoperative MRI scanning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tang, Zheng, Chen, Wang, Guo, Shu, Wu and Su.)

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions., Methods: Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions., Results: A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular-dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients., Conclusions: The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.

Background: Working memory (WM) deficit is considered a core feature and cognitive biomarker in patients with schizophrenia. Several studies have reported prominent object WM deficits in patients with schizophrenia, suggesting that visual WM in these patients extends to non-spatial domains. However, whether non-spatial WM is similarly affected remains unclear., Aim: This study primarily aimed to identify the processing of visual object WM in patients with first-episode schizophrenia., Methods: The study included 36 patients with first-episode schizophrenia and 35 healthy controls. Visual object WM capacity, including face and house WM capacity, was assessed by means of delayed matching-to-sample visual WM tasks, in which participants must distribute memory so that they can discriminate a target sample. We specifically examined their anhedonia experience by the Temporal Experience of Pleasure Scale and the Snaith-Hamilton Pleasure Scale. Cognitive performance was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)., Results: Both face and house WM capacity was significantly impaired in patients with schizophrenia. For both tasks, the performance of all the subjects was worse under the high-load condition than under the low-load condition. We found that WM capacity was highly positively correlated with the performance on RBANS total scores (r=-0.528, p=0.005), RBANS delayed memory scores (r=-0.470, p=0.013), RBANS attention scores (r=-0.584, p=0.001), RBANS language scores (r=-0.448, p=0.019), Trail-Making Test: Part A raw scores (r=0.465, p=0.015) and simple IQ total scores (r=-0.538, p=0.005), and correlated with scores of the vocabulary test (r=-0.490, p=0.011) and scores of the Block Diagram Test (r=-0.426, p=0.027) in schizophrenia. No significant correlations were observed between WM capacity and Positive and Negative Syndrome Scale symptoms., Conclusions: Our research found that visual object WM capacity is dramatically impaired in patients with schizophrenia and is strongly correlated with other measures of cognition, suggesting a mechanism that is critical in explaining a portion of the broad cognitive deficits observed in schizophrenia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Major Depressive Disorder (MDD) with childhood trauma is one of the functional subtypes of depression. Frequency-dependent changes in the amplitude of low-frequency fluctuations (ALFF) have been reported in MDD patients. However, there are few studies on ALFF about MDD with childhood trauma. Resting-state functional magnetic resonance imaging was used to measure the ALFF in 69 MDD patients with childhood trauma (28.7 ± 9.6 years) and 30 healthy subjects (28.12 ± 4.41 years). Two frequency bands (slow-5: 0.010-0.027 Hz; slow-4: 0.027-0.073 Hz) were analyzed. Compared with controls, the MDD with childhood trauma had decreased ALFF in left S1 (Primary somatosensory cortex), and increased ALFF in left insula. More importantly, significant group × frequency interactions were found in right dorsal anterior cingulate cortex (dACC). Our finding may provide insights into the pathophysiology of MDD with childhood trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Luo, Wu, Wu, Zheng, Yang, He, Ding, Yu and Peng.)

Affective temperaments and childhood-trauma experiences are associated with major depressive disorder (MDD). So far, how the covariation between distinct affective temperaments and childhood-trauma insulted brain functional connectivities (FCs) contribute to MDD remains unclear. Here, we aimed to investigate whether certain brain FC patterns are related to certain affective temperaments and whether the FCs contribute to depressive symptom dimensions of MDD patients. Twenty-nine medication-free MDD patients and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Two multivariate analyses of partial least squares (PLS) regression were used to explore the associations among childhood-trauma related resting-state FCs, affective temperaments and depressive symptom dimensions. In all participants, a linear combination of 81 FCs (involving parahippocampus, amygdala, cingulate cortex, insula, frontal-temporal-parietal-occipital cortex, pallidum, and cerebellum) were associated with a linear combination of increased depressive, irritable, anxious, and cyclothymic temperaments. Moreover, the covariation between the PLS FC profile and the PLS affective-temperament profile were enhanced in the MDD patients compared to healthy controls. In MDD participants alone, the affective-temperament modulated FC profile (mainly of the lingual and temporal cortex) was associated with the somatization symptom dimension when age, sex, ill-duration, age-of-onset, and HARS scores were adjusted. The findings imply possible neural correlates of affective temperaments and may find applications in intervention of the somatization-depression symptoms by stimulation of the related neural correlates., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Previous studies suggest that clozapine is commonly underutilized and that its initiation is delayed in patients with first-episode schizophrenia. Knowledge regarding clozapine use among Chinese patients with early-stage schizophrenia is limited. The aim of the present study was to investigate the point prevalence of and patterns and factors associated with clozapine use in patients with early-stage schizophrenia discharged from a psychiatric hospital in China., Methods: A retrospective study was conducted to analyze the prescriptions of 867 consecutive patients with early-stage schizophrenia who were admitted to the Affiliated Brain Hospital of Guangzhou Medical University between Jan 1, 2011 and Dec 31, 2016., Results: At discharge from the hospital, 114 (13.1%) patients were prescribed clozapine. Among the patients taking clozapine, 93 patients (81.6%) were prescribed clozapine polypharmacy, and only 21 patients (18.4%) were prescribed clozapine monotherapy. None of the patients were prescribed an overdose of clozapine. The mean daily dosage of clozapine was 160.97 mg, 149.05 mg and 213.69 mg among all patients taking clozapine, patients taking clozapine polypharmacy and patients taking clozapine monotherapy, respectively. The antipsychotic most frequently combined with clozapine was risperidone. Logistic regression suggested that the length of hospital stay, high school education, lower benzodiazepine use and antipsychotic polypharmacy were independently and significantly associated with clozapine use (P<0.05)., Conclusion: Although clozapine has been commonly used in China in recent years, the present study found that clozapine was not commonly used in patients with early-stage schizophrenia. An underutilization and delayed initiation of clozapine may exist in a portion of patients with early-stage schizophrenia. Given the unfavorable outcomes of underutilized and delayed clozapine use, future studies may be needed to assess and increase clozapine use in this population., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Yi et al.)

Schizophrenia patients often show impaired facial expression recognition, which leads to difficulties in adaptation to daily life. However, it remains unclear whether the deficit is at the perceptual or higher cognitive level of facial emotion processing. Recent studies have shown that earlier face-evoked event-related potential (ERP) components such as N170 and P100 can effectively distinguish schizophrenia patients from healthy controls; however, findings for later waveforms are ambiguous. To clarify this point, in this study we compared electroencephalographic signals in schizophrenia patients and control subjects during a facial expression judgment task. We found that group effects of the occipital N170 and frontal lobe contingent negative variation (CNV) were both significant. The effect sizes (ESs) of N170 and CNV amplitudes were generally medium or small, whereas that of CNV slope for an upright face was large (>0.8). Moreover, N170 amplitude and CNV slope but not CNV amplitude was correlated with Personal and Social Performance (PSP) Scale score. These results suggest that the slope of CNV drift during facial expression processing has a potential clinical value for schizophrenia., (Copyright © 2020 Wang, She, Luo, Li, Ning, Ren, Wu, Huang and Zheng.)

Purpose: Working memory (WM) deficits have been observed in people with schizophrenia (SZ) and are considered a core cognitive dysfunction in these patients. However, little is known about how stimuli and memory load influence visual WM deficits., Patients and Methods: In the present study, we adopted a match-to-sample task to examine the visual WM in 18 first-episode patients with SZ and 18 healthy controls (HCs). Faces and houses were used as the stimuli, and there were two levels of memory load - one item and two items; the average accuracy (ACC) and reaction time were calculated for each condition. The Positive and Negative Syndrome Scale and the Personal and Social Performance scale were used to assess the psychiatric symptoms and social function, respectively., Results: The results showed equivalent levels of WM deficit when using face and house stimuli. Moreover, the WM deficits were not related to the duration of illness, medication, or SZ symptoms., Conclusion: These results demonstrate that stimuli may have little impact on ACC in WM tasks in people with SZ. In addition, the memory load may have little impact on WM ACC when the load is relatively low., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

To investigate the emotional face processing in patients with schizophrenia, the preattentive automatic processing of emotional faces in individuals with schizophrenia was compared with that of age-matched healthy control group as indexed by the expressional mismatch negativity (EMMN) elicited by facial expressions. Compared with neutral faces as standard stimuli, deviant emotional faces elicited posterior EMMN between 150 and 500 ms after stimuli onset, with larger amplitudes for sad than happy deviant faces. Both early and late EMMNs significantly decreased in the schizophrenia group, regardless of sad or happy EMMN, in comparison with the healthy control group. These data suggest the dysfunction of automatic processing of expressional information in patients with schizophrenia.

People with schizophrenia exhibit impairments in target-speech recognition (TSR) against multiple-talker-induced informational speech masking. Up to date, the underlying neural mechanisms and its relationships with psychotic symptoms remain largely unknown. This study aimed to investigate whether the schizophrenia-associated TSR impairment contribute to certain psychotic symptoms by sharing underlying alternations in cortical gray-matter volume (GMV) with the psychotic symptoms. Participants with schizophrenia ( N = 34) and their matched healthy controls ( N = 29) were tested for TSR against a two-talker-speech masker. Psychotic symptoms of participants with schizophrenia were evaluated using the Positive and Negative Syndrome Scale. The regional GMV across various cortical regions was assessed using the voxel-based morphometry. The results of partial-correlation and mediation analyses showed that in participants with schizophrenia, the TSR was negatively correlated with the delusion severity, but positively with the GMV in the bilateral superior/middle temporal cortex, bilateral insular, left medial orbital frontal gyrus, left Rolandic operculum, left mid-cingulate cortex, left posterior fusiform, and left cerebellum. Moreover, the association between GMV and delusion was based on the mediating role played by the TSR performance. Thus, in people with schizophrenia, both delusions and the augmented vulnerability of TSR to informational masking are associated with each other and share the underlying cortical GMV reduction, suggesting that the origin of delusion in schizophrenia may be related to disorganized or limited informational processing (e.g., the incapability of adequately filtering information from multiple sources at the perceptual level). The TSR impairment can be a potential marker for predicting delusion severity.

Background: Speech recognition under noisy "cocktail-party" environments involves multiple perceptual/cognitive processes, including target detection, selective attention, irrelevant signal inhibition, sensory/working memory, and speech production. Compared to health listeners, people with schizophrenia are more vulnerable to masking stimuli and perform worse in speech recognition under speech-on-speech masking conditions. Although the schizophrenia-related speech-recognition impairment under "cocktail-party" conditions is associated with deficits of various perceptual/cognitive processes, it is crucial to know whether the brain substrates critically underlying speech detection against informational speech masking are impaired in people with schizophrenia., Methods: Using functional magnetic resonance imaging (fMRI), this study investigated differences between people with schizophrenia (n = 19, mean age = 33 ± 10 years) and their matched healthy controls (n = 15, mean age = 30 ± 9 years) in intra-network functional connectivity (FC) specifically associated with target-speech detection under speech-on-speech-masking conditions., Results: The target-speech detection performance under the speech-on-speech-masking condition in participants with schizophrenia was significantly worse than that in matched healthy participants (healthy controls). Moreover, in healthy controls, but not participants with schizophrenia, the strength of intra-network FC within the bilateral caudate was positively correlated with the speech-detection performance under the speech-masking conditions. Compared to controls, patients showed altered spatial activity pattern and decreased intra-network FC in the caudate., Conclusions: In people with schizophrenia, the declined speech-detection performance under speech-on-speech masking conditions is associated with reduced intra-caudate functional connectivity, which normally contributes to detecting target speech against speech masking via its functions of suppressing masking-speech signals.

Depressive symptoms are common in first episode schizophrenia. However, the prevalence and its associations of comorbid depressive symptoms with clinical variables are less well characterized in Chinese Han patients with schizophrenia. In this cross-sectional study, we recruited 240 first-episode and drug naïve (FEDN) inpatients with schizophrenia. All patients were rated on the 17-item Hamilton Depression Rating Scale (HAMD-17) to measure depressive symptoms, and also on the Positive and Negative Syndrome Scale (PANSS) for psychopathology. Our results showed that 131 patients had a total score of 8 or more points on HAMD-17, making the prevalence of comorbid depressive symptoms 54.6%. Fewer women (48.1%, 62 of 129) than men (62.2%, 69 of 111) had comorbid depressive symptoms. Compared to those patients without depressive symptoms, those with depressive symptoms showed higher PANSS total, general psychopathology, cognitive factor and negative symptom scores (all p<0.05). Further stepwise multiple logistic regression analysis indicated that the PANSS general psychopathology, the PANSS total score and gender (all p<0.05) remained significantly associated with depressive symptoms. In addition, correlation analysis showed significant correlations between HAMD total score and the following parameters: the PANSS general psychopathology, total score, and cognitive factor (Bonferroni corrected p's<0.05). Our results suggest that depressive symptoms occur with high prevalence in FEND schizophrenia in a Chinese Han population, and show association with general psychopathology, as well as with cognitive impairment., (Copyright © 2017. Published by Elsevier B.V.)

Background: Childhood trauma has long-term adverse effects on physical and psychological health. Previous studies demonstrated that suicide and mental disorders were related to childhood trauma. In China, there is insufficient research available on childhood trauma in patients with mental disorders., Methods: Outpatients were recruited from a psychiatric hospital in southern China, and controls were recruited from local communities. The demographic questionnaire, the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Social Support Rating Scale (SSRS) were completed by all participants, and the Self-rating Idea of Suicide Scale (SIOSS) were completed only by patients. Prevalence rates of childhood trauma were calculated. Kruskal-Wallis test and Dunnett test were used to compare CTQ-SF and SSRS scores between groups. Logistic regression was used to control demographic characteristics and examine relationships between diagnosis and CTQ-SF and SSRS scores. Spearman's rank correlation test was conducted to analyze relationships between suicidal ideation and childhood trauma and suicidal ideation and social support., Results: The final sample comprised 229 patients with depression, 102 patients with bipolar, 216 patient with schizophrenia, and 132 healthy controls. In our sample, 55.5% of the patients with depression, 61.8% of the patients with bipolar disorder, 47.2% of the patients with schizophrenia, and 20.5% of the healthy people reported at least one type of trauma. In patient groups, physical neglect (PN) and emotional neglect (EN) were most reported, and sexual abuse (SA) and physical abuse (PA) were least reported. CTQ-SF and SSRS total scores, and most of their subscale scores in patient groups were significantly different from the control group. After controlling demographic characteristics, mental disorders were associated with higher CTQ-SF scores and lower SSRS scores. CTQ-SF scores and number of trauma types were positively correlated with the SIOSS score. Negative correlations existed between SSRS scores and the SIOSS score., Limitations: Our sample may not be sufficiently representative. Some results might have been interfered by demographic characteristics. The SIOSS was not completed by controls. Data from self-report scales were not sufficiently objective., Conclusions: In southern China, childhood trauma is more severe and more prevalent in patients with mental disorders (depression, bipolar disorder and schizophrenia) than healthy people. Among patients with mental disorders in southern China, suicidal ideation is associated with childhood trauma and poor social support., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recent studies have reported that hyperhomocystinemia (HHcy) is highly prevalent in patients with bipolar disorder (BD), placing them at greater risk of cardiovascular disease and possibly serving as a disease biomarker. However, the correlation of HHcy with demographic or clinical parameters is not well known. In this study, we examined the prevalence of HHcy and its association with these parameters in a sample of Chinese BD patients. Fasting plasma homocysteine (Hcy) levels were determined in 198 BD inpatients and 84 healthy controls. HHcy was defined when Hcy concentration exceeded 15.0µmol/L. Affective symptomatology was assessed by the Young Mania Rating Scale, Hamilton Depression Rating Scale and the Clinical Global Impressions severity scale. Compared to healthy controls, BD patients had a significantly higher prevalence (34.85% vs. 19.05%) of HHcy and a higher absolute level of homocysteine. Logistic regression analysis demonstrated that BD patients with HHcy were more likely to be male, have elevated BMI, more frequent treatment on lithium but less on valproate. These results suggest that Chinese inpatients with bipolar disorder have a higher rate of HHcy than the general population, and those at greatest risk are male, have an elevated BMI, and take more lithium but less valproate therapy., (Copyright © 2017. Published by Elsevier B.V.)

Aims: This study aimed to investigate the mediating pathway of 3 factors (psychotic symptoms, attitude toward medication, and cognitive processing speed) on the effect of insight on personal-social functioning in patients with schizophrenia., Methods: Chinese inpatients with schizophrenia (n = 168; mean age 18 ± 50 years) diagnosed according to the DSM-IV were randomly assigned to treatment with antipsychotic medication alone or combined treatment. Positive and Negative Syndrome Scale (PANSS), Drug Attitude Inventory (DAI), Assessment of Insight (SAI), and Social-Personal Performance Scale (PSPS) scores were evaluated at baseline and at 3, 6, and 12 months. Cognitive function was assessed at baseline. Multiple mediation analyses were conducted with baseline data, end point data, and changes-in-scale scores between baseline and the end point, respectively., Results: At baseline and at 12 months, only psychotic symptoms mediated the effect of insight on personal-social functioning. For changes-in-scale scores over the 12-month follow-up, in patients receiving treatment with medication alone, the effect of improved insight on improved personal-social function was mediated by psychotic symptoms only; in patients receiving a combined treatment, the effect of improved insight on improved personal-social functioning was mediated by both psychotic symptoms and attitudes toward medication, independently., Conclusions: The link between insight and personal-social functions is mainly mediated by psychotic symptoms. Psychosocial intervention improves the predicting effect of insight on personal-social function by improving both the attitude toward medication and psychotic symptoms independently., (© 2018 S. Karger AG, Basel.)

Schizophrenia is considered a complex illness with multiple cognitive dysfunctions, including a deficit in visual processing. However, whether the deficiency of visual processing in schizophrenia is general across stimuli or stimulus-specific remains the subject of debate. In the current study, eighteen first-episode schizophrenic patients and eighteen healthy controls participated in three visual search tasks in which they were asked to search a specific target of a triangle, face identity or facial affect. The results showed that, compared to healthy controls, the accuracies for face identity and facial affect searches were significantly lower in schizophrenic patients, while the performance of the triangle search was the same. Furthermore, the accuracy of the facial affect search was negatively correlated to negative symptoms in schizophrenia. These results revealed a face-related deficit in schizophrenia and suggest that visual processing deficits in schizophrenia were stimuli-specific., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The superior temporal gyrus (STG) is involved in speech recognition against informational masking under cocktail-party-listening conditions. Compared to healthy listeners, people with schizophrenia perform worse in speech recognition under informational speech-on-speech masking conditions. It is not clear whether the schizophrenia-related vulnerability to informational masking is associated with certain changes in FC of the STG with some critical brain regions. Using sparse-sampling fMRI design, this study investigated the differences between people with schizophrenia and healthy controls in FC of the STG for target-speech listening against informational speech-on-speech masking, when a listening condition with either perceived spatial separation (PSS, with a spatial release of informational masking) or perceived spatial co-location (PSC, without the spatial release) between target speech and masking speech was introduced. The results showed that in healthy participants, but not participants with schizophrenia, the contrast of either the PSS or PSC condition against the masker-only condition induced an enhancement of functional connectivity (FC) of the STG with the left superior parietal lobule and the right precuneus. Compared to healthy participants, participants with schizophrenia showed declined FC of the STG with the bilateral precuneus, right SPL, and right supplementary motor area. Thus, FC of the STG with the parietal areas is normally involved in speech listening against informational masking under either the PSS or PSC conditions, and declined FC of the STG in people with schizophrenia with the parietal areas may be associated with the increased vulnerability to informational masking., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

Integrated care can reduce rate of relapse and improve personal and social functions in patients with schizophrenia. We established and evaluated a new model of "intensive-consolidation" two-stage integrated care (IC) for inpatients with schizophrenia. Data were collected between 2012 and 2015. Chinese inpatients with schizophrenia (n=170) diagnosed according to DSM-IV were randomly assigned to antipsychotic medication-alone (n=84) or two-stage IC (n=86) and followed up for 12 months. The IC model included intensive treatments (antipsychotics plus the cognitive behavior therapy and rehabilitation treatment) during hospitalization and 3-time consolidation treatments with 3-month intervals at clinics. Outcome measures included the rate of relapse, psychiatric symptoms and social functioning. Compared with medication-alone group, the rate of relapse were significantly lower in IC group (p=0.012); the Mixed-Effects Model for Repeated-Measures analyses showed that the IC group significantly improved in positive symptoms over time; greater improvement in self-care and less aggressive behaviors were observed over time in IC group (all p<0.008). The findings support the feasibility and effectiveness of the new two-stage model of integrated care as an intervention for middle-acute-phase inpatients with schizophrenia. The model is particularly informative to countries where medical resources are mainly distributed in developed regions., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

The use of event-related potential (ERP) recording technology during perceptual and cognitive processing has been studied in order to develop objective diagnostic indexes for people with neuropsychiatric disorders. For example, patients with schizophrenia exhibit consistent abnormalities in face-evoked early components of ERPs and mismatch negativities (MMNs). In most studies, the choice of reference has been the average reference (AVE), but whether this is the most suitable choice is still unknown. The aim of this study was to systematically compare the AVE and reference electrode standardization technique (REST) methods for assessing expressional face-evoked early visual ERPs and visual MMNs (vMMNs) in patients with schizophrenia and healthy controls. The results showed that both the AVE and REST methods could: (1) obtain primary visual-evoked ERPs in the two groups, (2) reveal the neutral and emotional expression discrimination deficit of the P1 component in the patients, which was normal in the healthy controls, (3) reflect reductions of happy vMMNs in the patients compared to the healthy controls, and (4) show right-dominant sad vMMNs only in the patients. On the other hand, compared to the energy distributions of the AVE-obtained potentials, those of REST-obtained early visual ERPs and vMMNs were more concentrated around the temporo-occipital areas. Furthermore, only the REST-obtained vMMNs revealed a significant difference between happy and sad mismatch stimuli in patients with schizophrenia. These results demonstrate that REST technology might provide new insights into neurophysiological factors associated with neuropsychiatric disorders.

Obesity is a common comorbidity in schizophrenia. Few studies have addressed obesity in Chinese schizophrenia patients. The aims of this current study were to evaluate the prevalence, risk factors and clinical correlates of obesity in Chinese patients with schizophrenia. A total of 206 patients were recruited from a hospital in Beijing. Their clinical and anthropometric data together with plasma glucose and lipid parameters were collected. Positive and Negative Syndrome Scale (PANSS) was rated for all patients. Overall, 43 (20.9%) patients were obese and 67 (32.5%) were overweight. The obese patients had significantly higher glucose levels, triglyceride levels than non-obese patients. Females and patients with type 2 diabetes mellitus had increased risk for obesity. Correlation analysis showed that BMI was associated with sex, education levels, negative symptoms, total PANSS score, triglyceride levels and type 2 diabetes mellitus. Further stepwise regression analysis showed that sex, type 2 diabetes, education level, triglyceride and amount of smoking/day were significant predictors for obesity. Our study showed that the prevalence of obesity in Chinese patients with schizophrenia is higher than that in the general population. Some demographic and clinical variables are risk factors for obesity in schizophrenia., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Long-term antipsychotic treatment for schizophrenia is associated with the development of tardive dyskinesia (TD), which is involved in increased cognitive impairment. Dopamine beta-hydroxylase (DBH) gene associated with dopamine and norepinephrine systems influences cognition. Schizophrenia with TD have higher DBH activity than those without TD. This study examined whether DBH5'-insertion/deletion (-Ins/Del) polymorphism could influence cognitive function in schizophrenia with and without TD. The presence of DBH5'-Ins/Del polymorphism was determined in 345 schizophrenia with TD and 397 schizophrenia without TD. The Abnormal Involuntary Movement Scale and Repeatable Battery for Assessment of Neuropsychological Status (RBANS) were used to assess TD severity and cognition. The allele and genotype frequencies of DBH5'-Ins/Del polymorphism did not differ between patients with and without TD (both p>0.05). RBANS total score and subscales did not differ by DBH5'-Ins/Del genotype groups in patients with TD (all p>0.05). However, attention score significantly differed by DBH5'-Ins/Del genotype groups in those without TD (p<0.05). Patients without TD who were Del homozygous had significantly lower attention score than those without TD who were Ins alleles (p<0.05). Immediate memory and attention scores were lower in patients with TD than without TD (both p<0.05). This study indicated that DBH5'-Ins/Del polymorphism may not play a role in the susceptibility to TD and cognitive deficits in schizophrenia with TD, but it may influence cognitive function in schizophrenia with non-TD. Moreover, schizophrenia with TD experienced greater cognitive deficits than those with non-TD, especially in immediate memory and attention., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Under a "cocktail-party" listening condition with multiple-people talking, compared to healthy people, people with schizophrenia benefit less from the use of visual-speech (lipreading) priming (VSP) cues to improve speech recognition. The neural mechanisms underlying the unmasking effect of VSP remain unknown. This study investigated the brain substrates underlying the unmasking effect of VSP in healthy listeners and the schizophrenia-induced changes in the brain substrates. Using functional magnetic resonance imaging, brain activation and functional connectivity for the contrasts of the VSP listening condition vs. the visual non-speech priming (VNSP) condition were examined in 16 healthy listeners (27.4 ± 8.6 years old, 9 females and 7 males) and 22 listeners with schizophrenia (29.0 ± 8.1 years old, 8 females and 14 males). The results showed that in healthy listeners, but not listeners with schizophrenia, the VSP-induced activation (against the VNSP condition) of the left posterior inferior temporal gyrus (pITG) was significantly correlated with the VSP-induced improvement in target-speech recognition against speech masking. Compared to healthy listeners, listeners with schizophrenia showed significantly lower VSP-induced activation of the left pITG and reduced functional connectivity of the left pITG with the bilateral Rolandic operculum, bilateral STG, and left insular. Thus, the left pITG and its functional connectivity may be the brain substrates related to the unmasking effect of VSP, assumedly through enhancing both the processing of target visual-speech signals and the inhibition of masking-speech signals. In people with schizophrenia, the reduced unmasking effect of VSP on speech recognition may be associated with a schizophrenia-related reduction of VSP-induced activation and functional connectivity of the left pITG.

Patients with schizophrenia consistently exhibit abnormalities in the N170 event-related potential (ERP) component evoked by images of faces. However, the relationship between these face-specific N170 abnormalities in patients with schizophrenia and the clinical characteristics of this disorder has not been elucidated. Here, ERP recordings were conducted for patients with schizophrenia and healthy controls. The amplitude and latency of the N170 component were recorded while participants passively viewed face and non-face (table) images to explore the correlation between face-specific processing and clinical characteristics in schizophrenia. The results provided evidence for a face-specific N170 latency delay in patients with schizophrenia. The N170 latency in patients with schizophrenia was significantly longer than that in healthy controls when images of faces were presented in both upright and inverted orientations. Importantly, the face-related N170 latencies of the left temporo-occipital electrodes (P7 and PO7) were positively correlated with both negative and general psychiatric symptoms in these patients. The N170 amplitudes were weaker in patients than in controls for inverted images of both faces and non-faces (tables), with a left-hemisphere dominance. The face inversion effect (FIE), meaning the difference in N170 amplitude between upright and inverted faces, was absent in patients with schizophrenia, suggesting an abnormality of holistic face processing. Together, these results revealed a marked symptom-relevant neural delay associated with face-specific processing in patients with schizophrenia, providing additional evidence to support the demyelination hypothesis of schizophrenia.

Structural abnormalities in schizophrenia (SZ) patients have been well documented with structural magnetic resonance imaging (MRI) data using voxel-based morphometry (VBM) and region of interest (ROI) analyses. However, these analyses can only detect group-wise differences and thus, have a poor predictive value for individuals. In the present study, we applied a machine learning method that combined support vector machine (SVM) with recursive feature elimination (RFE) to discriminate SZ patients from normal controls (NCs) using their structural MRI data. We first employed both VBM and ROI analyses to compare gray matter volume (GMV) and white matter volume (WMV) between 41 SZ patients and 42 age- and sex-matched NCs. The method of SVM combined with RFE was used to discriminate SZ patients from NCs using significant between-group differences in both GMV and WMV as input features. We found that SZ patients showed GM and WM abnormalities in several brain structures primarily involved in the emotion, memory, and visual systems. An SVM with a RFE classifier using the significant structural abnormalities identified by the VBM analysis as input features achieved the best performance (an accuracy of 88.4%, a sensitivity of 91.9%, and a specificity of 84.4%) in the discriminative analyses of SZ patients. These results suggested that distinct neuroanatomical profiles associated with SZ patients might provide a potential biomarker for disease diagnosis, and machine-learning methods can reveal neurobiological mechanisms in psychiatric diseases., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: Focal cortical dysplasia (FCD) type IIb is a cortical malformation characterized by cortical architectural abnormalities, dysmorphic neurons, and balloon cells. It has been suggested that FCDs are caused by somatic mutations in cells in the developing brain. Here, we explore the possible involvement of somatic mutations in FCD type IIb., Methods: We collected a total of 24 blood-brain paired samples with FCD, including 13 individuals with FCD type IIb, 5 with type IIa, and 6 with type I. We performed whole-exome sequencing using paired samples from 9 of the FCD type IIb subjects. Somatic MTOR mutations were identified and further investigated using all 24 paired samples by deep sequencing of the entire gene's coding region. Somatic MTOR mutations were confirmed by droplet digital polymerase chain reaction. The effect of MTOR mutations on mammalian target of rapamycin (mTOR) kinase signaling was evaluated by immunohistochemistry and Western blotting analyses of brain samples and by in vitro transfection experiments., Results: We identified four lesion-specific somatic MTOR mutations in 6 of 13 (46%) individuals with FCD type IIb showing mutant allele rates of 1.11% to 9.31%. Functional analyses showed that phosphorylation of ribosomal protein S6 in FCD type IIb brain tissues with MTOR mutations was clearly elevated, compared to control samples. Transfection of any of the four MTOR mutants into HEK293T cells led to elevated phosphorylation of 4EBP, the direct target of mTOR kinase., Interpretation: We found low-prevalence somatic mutations in MTOR in FCD type IIb, indicating that activating somatic mutations in MTOR cause FCD type IIb., (© 2015 American Neurological Association.)

Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. Activation of microglia is a key event in the reaction of the cerebral immune system to pathological changes. It can be hypothesized that microglia contribute to the neuropathology of schizophrenia. In this study, at embryonic day (ED) 9 pregnant mice were treated with intraperitoneal injection of polyriboinosinic-polyribocytidilic acid (Poly I:C) at a single dose of 20 mg/kg. At postnatal day 42, descendants were treated with minocycline (40 mg/kg) or saline for consecutive 14 days. Behavioral changes (locomotor activity, social interaction, and prepulse inhibition) were examined and the number of microglia was assessed after the treatment. The adult offspring exposed to Poly I:C at ED 9 showed behavioral changes (hyperlocomotion, deficits in social interaction and prepulse inhibition) and significant microglial activation in these brain areas (hippocampus, thalamus, and cerebral cortex) compared to those in saline-injected group. Moreover, minocycline attenuated the behavioral deficits and inhibited the activated microglia. These findings suggest that maternal infection may contribute to microglial activation in the offspring. In addition, the effect of minocycline in this immune model may be related to the inhibition of microglial activation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Several lines of evidence have suggested that the dysregulation of immune system is involved in the pathogenesis of schizophrenia. Microglia are the resident macrophage of the brain and the major player in innate immunity in the brain. We hypothesized that microglia activation may be closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (PD7), and they were separately treated with saline or minocycline for consecutive 3days. Behavioral changes (locomotor activity, social interaction and prepulse inhibition) were examined in adulthood, and the number of microglia was assessed using immunohistochemistry at PD9, PD21 and PD67. The adult rats in LPS-injected group showed obvious behavioral alterations (deficits in social behavior and prepulse inhibition) and a persistently dramatic increase of number of activated microglial cells in the hippocampus, cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, pretreatment with minocycline could significantly rescue the behavioral deficits and prevent microglia activation. Our results suggest that neonatal intrahippocampal LPS injection may serve as a potential schizophrenia animal model, and inhibition of microglia activation may be a potential treatment strategy for schizophrenia., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Various signs of activation of microglia have been reported in schizophrenia, and it is hypothesized that microglia activation is closely associated with the neuropathology of schizophrenia., Methods: Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (P7), and they were separately given saline, risperidone (0.5 mg/kg), minocycline (40 mg/kg) or a combination of both of them at P42 for consecutive 14 days. Behavioral changes (locomotion activity, social interaction, novel object recognition and prepulse inhibition) were examined and the number of microglia was assessed by using immunohistochemistry in adulthood., Results: The adult rats in LPS-injected group showed obvious behavioral alteration (e. g. deficits in social interaction, novel object recognition and prepulse inhibition) and a dramatic increase of number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, application of either minocycline, risperidone or both of them significantly rescued behavioral deficits and attenuated microglia activation., Conclusion: Our results suggest that inhibition of microglia activation may be one of mechanisms underlying the antipsychotic effect of minocycline and risperidone.