Corrigendum: The association between metabolic disturbance and cognitive impairments in early-stage schizophrenia.

[This corrects the article DOI: 10.3389/fnhum.2020.599720.].

Bullectomy used to treat a patient with pulmonary vesicles related to COVID-19: A case report.

BACKGROUND: The corona virus disease 2019 (COVID-19) has been a pandemic for more than one year and estimated to affect the whole world in the near future. CASE SUMMARY: Here we reported that one COVID-19 patient with vesicles was treated by bullectomy. The patient's perioperative laboratory tests were analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. CONCLUSION: This patient with vesicles underwent bullectomy and had a poor prognosis. He showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. We hope our report will be of interest for clinicians who will treat COVID-19 patients in the future.

Corrigendum: The association between cognitive deficits and clinical characteristic in first-episode drug naïve patients with schizophrenia.

[This corrects the article DOI: 10.3389/fpsyt.2021.638773.].

Developments in Biological Mechanisms and Treatments for Negative Symptoms and Cognitive Dysfunction of Schizophrenia.

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade. The first part of this review summarizes the pathogenesis of schizophrenia, especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics. The second part describes the novel medications and several advanced physical therapies (e.g., transcranial magnetic stimulation and transcranial direct current stimulation) for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

Corrigendum: The Association Between Cognitive Deficits and Clinical Characteristic in First-Episode Drug Naïve Patients With Schizophrenia.

[This corrects the article DOI: 10.3389/fpsyt.2021.638773.].

The Association Between Cognitive Deficits and Clinical Characteristic in First-Episode Drug Naïve Patients With Schizophrenia.

Background: Schizophrenia is a severe mental disease which characterized by positive symptom, negative symptom, general pathology syndrome and cognitive deficits. In recent years, many studies have investigated the relationship between cognitive deficits and clinical characteristics in schizophrenia, but relatively few studies have been performed on first-episode drug-naïve patients. Methods: Eighty seven first-episode drug-naïve schizophrenia patients were assessed for positive symptom, negative symptom, general pathology symptom and cognitive deficits from the Positive and Negative Symptom Scale and MATRICS Consensus Cognitive Battery. Psychotics depression were assessed using the Calgary depressing scale for schizophrenia. The relationship between clinical characteristics and cognitive deficits were assessed using correlation analysis and linear regression analysis. Results: The prevalence of cognitive deficits among the patients in our study was 85.1% (74/87) which was much higher than that in the general population. According to correlation analysis, negative symptom was negatively correlated with speed of processing and social cognition, and general pathology showed a negative correlation with attention/vigilance. In addition, a positive correlation was found between age and speed of processing. No correlation was found between cognitive deficits and positive symptom. Conclusions: This study confirmed that negative symptom is negatively related with some domains of cognitive function in first-episode drug naïve schizophrenia patients. Trail Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients

Weight gain and metabolic disturbances, potentially influenced by increased appetite, are common effects of olanzapine treatment in patients with schizophrenia. In this study, we explored the association between olanzapine-induced weight gain and metabolic effects with increased appetite. Drug-naïve, first-episode schizophrenia patients were treated with olanzapine for 12 weeks. Assessments included time to increased appetite, body weight, body mass index, biochemical indicators of blood glucose and lipids, proportion of patients who gained more than 7% or 10% of their baseline weight upon treatment conclusion, patients who developed dyslipidemia, and Positive and Negative Syndrome Scale scores. In total, 33 patients with schizophrenia receiving olanzapine were enrolled and 31 completed the study. During the 12-week olanzapine treatment, 77.4% (24/31) patients had increased appetite with 58.1% (18/31) patients having increased appetite within the first 4 weeks. The mean time for increased appetite was 20.3 days. More patients in the increased appetite group increased their initial body weight by more than 7% after 12 weeks when compared to patients with unchanged appetite (22/24 [91.7%] vs. 3/7 [42.9%], p = 0.004). Earlier increased appetite led to more weight gain during the following month. Overall, 50% of patients in the increased appetite group had dyslipidemia after 12 weeks. Our results demonstrated that olanzapine induced significantly appetite increase in first-episode patients with schizophrenia and appetite increase played a key role in olanzapine-induced weight gain and dyslipidemia. Clinical Trial Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).

Corrigendum: Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients.

[This corrects the article DOI: 10.3389/fphar.2020.00739.].

The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia.

Background: Cognitive impairment is one of the core symptoms of schizophrenia, which is considered to be significantly correlated to prognosis. In recent years, many studies have suggested that metabolic disorders could be related to a higher risk of cognitive defects in a general setting. However, there has been limited evidence on the association between metabolism and cognitive function in patients with early-stage schizophrenia. Methods: In this study, we recruited 172 patients with early-stage schizophrenia. Relevant metabolic parameters were examined and cognitive function was evaluated by using the MATRICS Consensus Cognitive Battery (MCCB) to investigate the relationship between metabolic disorder and cognitive impairment. Results: Generally, the prevalence of cognitive impairment among patients in our study was 84.7% (144/170), which was much higher than that in the general population. Compared with the general Chinese setting, the study population presented a higher proportion of metabolic disturbance. Patients who had metabolic disturbance showed no significant differences on cognitive function compared with the other patients. Correlation analysis showed that metabolic status was significantly correlated with cognitive function as assessed by the cognitive domain scores (p < 0.05), while such association was not found in further multiple regression analysis. Conclusions: Therefore, there may be no association between metabolic disorder and cognitive impairment in patients with early-stage schizophrenia. Trial Registration: Clinicaltrials.gov, NCT03451734. Registered March 2, 2018 (retrospectively registered).

Effects of Aspirin in Rats With Ouabain Intracerebral Treatment-Possible Involvement of Inflammatory Modulation?

Bipolar disorder (BD) is a chronic and refractory disease with high probability of morbidity and mortality. Although epidemiological studies have established a strong association between BD and immune dysfunction, the precise etiology is still debatable, and the underpinning mechanism remains poorly investigated and understood. In the present study, manic-like symptoms of BD were induced in rats after intracerebroventricular administration of ouabain. Aspirin, a commonly used anti-inflammatory agent, was used to treat the induced manic-like symptoms and inflammation. Concentrations of a spectrum of inflammatory cytokines were examined by enzyme-linked immunosorbent assay in both plasma and brain tissues, and expression of Toll-like receptors 3 and 4 were determined in rat brains. Locomotor activity was monitored with open-field test to assess the effects of ouabain challenge and to evaluate the treatment efficacy of aspirin. Ouabain administration recapitulated many mania-like features such as increased stereotypic counts, traveling distance in open-field test, and decreased expression of brain-derived neurotrophic factor, interferon gamma, and Toll-like receptor 3, which were frequently found in patients with BD. These abnormalities could be partially reversed by aspirin. Our findings suggest that aspirin could be used as a promising adjunctive therapy for BD.

Increased frontal gray matter volume in individuals with prodromal psychosis.

BACKGROUND: Brain anatomical deficits associated with cognitive dysfunction have been reported in patients with schizophrenia. However, it remains unknown whether such anatomical deficits exist in individuals with prodromal psychosis. The present study is designed to investigate anatomical deficits in prodromal individuals and their associations with clinical/cognitive features. METHODS: Seventy-four prodromal individuals and seventy-six healthy controls were scanned using structural magnetic resonance imaging. Support vector machines were applied to test whether anatomical deficits might be used to discriminate prodromal individuals from healthy controls. RESULTS: Prodromal individuals showed significantly increased gray matter volume (GMV) in the right inferior frontal gyrus (IFG) and right rectus gyrus relative to healthy controls. No correlations were observed between increased GMV and clinical/cognitive characteristics. The combination of increased GMV in the right rectus gyrus and right IFG showed a sensitivity of 74.32%, a specificity of 67.11%, and an accuracy of 70.67% in differentiating prodromal individuals from healthy controls. CONCLUSION: Our results provide evidence of increased frontal GMV in prodromal individuals. A combination of GMV values in the two frontal brain areas may serve as potential markers to discriminate prodromal individuals from healthy controls. The results thus highlight the importance of the frontal regions in the pathophysiology of psychosis.

The reliability and validity of a newly developed self-rating functional scale compared with Personal and Social Performance Scale and World Health Organization Disability Assessment Schedule II.

A new self-rating functional scale (SRFS) was developed to assess the functionality of patients with schizophrenia, referred to the structure of Personal and Social Performance Scale (PSP). The main aim of this study was to evaluate the reliability and validity of the SRFS. A total of 210 patients with schizophrenia were recruited from outpatient clinics in six sites in China. Demographic information, SRFS, PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale were assessed. Spearman's correlation coefficient and path analysis were used to assess the reliability and validity of the SRFS. Cronbach's α coefficient was used to assess the internal consistency reliability. Cronbach's α was 0.83, and ranged from 0.80 to 0.82 stably, indicating that the scale was reliable in internal consistency. Spearman's correlation coefficient between split two parts was 0.68 (P<0.01), suggesting a moderate to strong split-half reliability. The standardized regression coefficients ranged from 0.48 to 0.79, indicating moderate construct validity. Spearman's correlation coefficients between SRFS and PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale are 0.59, 0.65, and 0.47 (all P<0.01), respectively, indicating moderate criteria validities. The SRFS is a reliable and valid instrument for assessing personal and social functionality in patients with schizophrenia.

Maternal dietary patterns, supplements intake and autism spectrum disorders: A preliminary case-control study.

The aim of this study was first to investigate associations between maternal dietary patterns and autism spectrum disorders (ASDs) and second to investigate association between maternal supplement intake and ASD.We used a case-control study design to enroll typically developing (TD) children and children with ASD, and data were derived from the Autism Clinical and Environmental Database (ACED).Three seventy four children with AUTISM and 354 age matched TD children were included. The multivariate logistic regression model revealed that maternal unbalanced dietary patterns before conception had a significant increased risk of ASD in offspring (mostly meat: adjusted OR, 4.010 [95% CI, 1.080, 14.887]; mostly vegetable: adjusted OR, 2.234 [95% CI, 1.009, 4.946]); maternal supplementation of calcium during pregnancy preparation was associated with decreased ASD risk (adjusted OR, 0.480 [95% CI, 0.276, 0.836]).This study provided preliminary evidence that maternal unbalanced dietary patterns may be a risk factor for ASD and supplementation of calcium during pregnancy preparation may be inversely associated with ASD in offspring.

Social impairment of children with autism spectrum disorder affects parental quality of life in different ways.

This study evaluated the life quality of Chinese parents of preschool children with autism spectrum disorder (ASD) and their association with child social impairment and childcare burden. The participants included 406 families of children with ASD and 513 families with typically developing (TD) children. The findings indicated that parents in the ASD group had a lower quality of life than parents in the TD group, whereas only mother of children with ASD experienced a greater childcare burden than mother with TD children. Lower parental quality of life were associated with higher social impairment of children. To further clarify the correlativity of child social impairment, parental quality of life and childcare burden, the mediation analyses were conducted. The results showed that childcare burden mediated the influence of child social impairment on maternal quality of life, while it has no mediating effect on fathers. It implies that social impairment of children affects parental quality of life in different ways.

Altered functional connectivity strength and its correlations with cognitive function in subjects with ultra-high risk for psychosis at rest.

AIMS: Evidence of altered structural and functional connectivity in the frontal-occipital network is associated with cognitive deficits in patients with schizophrenia. However, the altered patterns of functional connectivity strength (FCS) in individuals with ultra-high risk (UHR) for psychosis remain unknown. In this study, whole-brain FCS was assessed to examine the altered patterns of FCS in UHR subjects. METHODS: A total of 34 UHR subjects and 37 age- and sex-matched healthy controls were enrolled to undergo resting-state functional magnetic resonance imaging. The imaging data were analyzed using the graph theory method. RESULTS: Compared with healthy controls, UHR subjects showed significantly decreased FCS in the left middle frontal gyrus and significantly increased FCS in the left calcarine cortex. The FCS values in the left middle frontal gyrus were positively correlated to the scores of the Brief Assessments of Cognitionin Schizophrenia Symbol Coding Test (r = 0.366, P = 0.033) in the UHR subjects. A negative correlation was found between the FCS values in the left calcarine cortex and the scores of the Stroop color-naming test (r = -0.475, P = 0.016) in the UHR subjects. A combination of the FCS values in the 2 brain areas showed an accuracy of 87.32%, a sensitivity of 73.53%, and a specificity of 100% for distinguishing UHR subjects from healthy controls. CONCLUSIONS: Significantly altered FCS in the frontal-occipital network is observed in the UHR subjects. Furthermore, decreased FCS in the left middle frontal gyrus and increased FCS in the left calcarine have significant correlations with the cognitive measures of the UHR subjects and thus improve our understanding of the underlying pathophysiological mechanisms of schizophrenia. Moreover, a combination of the FCS values in the 2 brain areas can serve as a potential image marker to distinguish UHR subjects from healthy controls.

Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder.

Aggressive behaviors of children with autism spectrum disorder (ASD) are common. We conducted this study to describe the aggressive mode of preschool children with ASD and examine the associations between specific aggressive behaviors and two treatable factors: sleep problems and attention deficit hyperactivity disorder (ADHD) symptoms. In total, 577 typically developing (TD) children and 490 children with ASD were investigated in this study. The Institute for Basic Research - Modified Overt Aggression Scale (IBR-MOAS) was used to assess aggressive behaviors. Children's social impairments, sleep problems and ADHD symptoms were also measured with specific scales. The total IBR-MOAS score was significantly higher (worse) in the TD group [4.47 (5.36)] than in the ASD group [3.47 (5.63), P = 0.004]. The aggressive modes differed between groups: when compared with each other, the TD group received higher scores on Verbal and Physical Aggression Toward Others (all P < 0.01), while the ASD group had higher scores on Physical Aggression Against Self (P = 0.006). The linear regression model demonstrated that the aggressive behaviors of children with ASD were significantly associated with two treatable factors: sleep problems and ADHD symptoms. These findings have substantial clinical implications: treatment of these two risk factors may be helpful in managing aggressive behavior in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1155-1162. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Contribution of long duration of undiagnosed bipolar disorder to high frequency of relapse: A naturalistic study in China.

BACKGROUND: With attention to misdiagnosis of bipolar disorder (BP), long duration of undiagnosed bipolar disorder (DUBP) had been reported recently in years. This study aims to investigate the contributions of long DUBP to the frequency of relapse in bipolar patients, and explore affect factors of DUBP. METHOD: From 26 hospitals throughout China, 3896 participants diagnosed with BP according to International Classification of Diseases 10th criteria were enrolled in this study. Socio-demographic and clinical data were collected from medical records and specific questionnaires through clinical interviews with patients and their relatives. RESULTS: (1) Our results showed that the mean of DUBP was 40.52months. In total, 779 patients (19.995%) reported DUBP greater than 5years, and 1931 patients (49.564%) reported their DUBP greater than 2years. The number of mood episodes was averaged 5.44, and the frequency ratio of (hypo) mania to depressive episodes was 1.49 (3.27/2.19). (2) Multiple linear regression analysis revealed that DUBP was significantly contributed to the number of relapse (Beta=0.072, p<0.001) after considering the confounding including gender, age at study entry, age of onset, age of first (hypo) manic episodes, age of first depressive episodes, type of first episodes and family history of mental illness. (3) Factors including age at the study entry (Beta=0.526, p<0.001), age of onset (Beta=-1.654, p<0.001), age of first (hypo) manic episode (Beta=0.348, p<0.001), age of first depressive episode (Beta=0.983, p<0.001), depression as the type of first episode (Beta=0.058, p<0.001) and family history of mental illness (Beta=0.029, p<0.05) were significantly contributed to long DUBP. CONCLUSION: It was concluded that long DUBP might lead to high frequent relapse in bipolar patients. The factors correlated with long DUBP include older age, early age of onset, depression as the type of first episode and family history of mental illness. The findings of our study suggest emergency task to early reorganization of bipolar disorder, and improving clinicians' recognition of bipolar disorder from patients with depressive episodes, especially in children and adolescents.

Association Between Maternal Obesity and Autism Spectrum Disorder in Offspring: A Meta-analysis.

As the link between maternal obesity and risk of autism among offspring is unclear, the present study assessed this association. A systematic search of an electronic database was performed to identify observational studies that examined the association between maternal obesity and autism. The outcome measures were odds ratios comparing offspring autism risk between obese and normal-weight mothers. Five observational studies were included in the meta-analysis. A fixed-effects model was used since low heterogeneity was observed between studies. The pooled adjusted odds ratio was 1.47 (95 % CI 1.24-1.74). The meta-analysis results support an increased risk of autism spectrum disorder in children of women who were obese during pregnancy. However, further study is warranted to confirm these results.

Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population.

BACKGROUND: Human P-glycoprotein encoded by the ATP-binding cassette sub-family B member 1 (ABCB1) gene is expressed in the blood-brain barrier. ABCB1 protects the brain from many drugs and toxins such as glucocorticoids through the efflux pump. Recent evidence suggests that a specific allele of the ABCB1 gene confers susceptibility to major depressive disorder (MDD) in the Japanese population. The aim of this study was to explore the association of ABCB1 gene polymorphisms with MDD in a local Chinese Han population. METHODS: Two hundred and ninety-two MDD patients and 208 unrelated individuals were matched by age and sex and examined using a case-control design. Six single nucleotide polymorphisms (SNPs) of the ABCB1 gene, including rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, and rs2235015, were genotyped by ligase detection reaction and multiplex polymerase chain reaction. Linkage disequilibrium and haplotype analysis were investigated in the two study groups. RESULTS: Significant protection for MDD individuals carrying the TG haplotype of rs1045642-rs2032582 was observed (odds ratio 0.470, 95% confidence interval 0.251-0.897, P=0.01). The rs2032582 (G2677T) and rs1128503 (C1236T) SNPs of ABCB1 showed nominal associations with MDD; the other four SNPs of the ABCB1 gene were not associated with MDD. CONCLUSION: Chinese individuals carrying the TG haplotype of rs1045642-rs2032582 had a nearly 53% lower risk of developing MDD. To the best of our knowledge, this is the first report to analyze the effect of ABCB1 polymorphism on the risk of MDD in a Chinese population.