Family-based genetic analysis in schizophrenia by whole-exome sequence to identify rare pathogenic variants.

Schizophrenia (SCZ) is influenced by a combination of genetic and environmental factors. Although several studies have been conducted to identify the causative loci and genes, few of these loci or genes can be repeated due to the high phenotypic and genetic heterogeneity of disease, and their mechanisms are not fully understood. There may be some "missing heritability" that has not yet been found. In order to investigate the deleterious heritable mutations, whole-exome sequencing (WES) in pedigrees with SCZ was used in the current work. Two unrelated pedigrees with SCZ were recruited to perform WES. Genetic analysis was next performed to find potential variants in accordance with the prioritized strategy. Followed by genetic analysis to detect candidate variants according to the prioritized strategy. Next, a series of algorithms was used to predict the pathogenicity of variants. Sanger sequencing was finally conducted to verify the co-segregation. Recessive mutations in six genes (TFEB, SNAI2, TFAP2B, PRKDC, ST18 in Pedigree 1 and PKHD1L1 in Pedigree 2) that co-segregated with SCZ in two families were discovered through genetic analysis by WES. Sanger sequencing verified that all of the mutations in the affected siblings were homozygous. These results corroborated the hypothesis that SCZ exhibits strong heterogeneity and complex inheritance patterns. The newly discovered homozygous variations deepen our understanding of the mutation spectrum and offer more proof for the involvement of TFEB, SNAI2, TFAP2B, PRKDC, ST18, and PKHD1L1 in the development of SCZ.

Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia.

Schizophrenia (SCZ) is a prevalent, severe, and persistent mental disorder with an unknown etiology. Growing evidence indicates that immunological dysfunction is vital in the development of SCZ. Our study aims to uncover potential immune-linked hub genes and immune infiltration characteristics of SCZ, as well as to develop a diagnostic model based on immune-linked central genes. GSE38484 and GSE54913 chip expression data for patients with SCZ and healthy controls were retrieved. Weighted gene co-expression network analysis (WGCNA) was performed to identify major module genes and critical immune-linked genes. Functional enrichment analysis was conducted to elucidate the involvement of key genes in the immunological response to SCZ, along with the examination of their protein interactions. Moreover, 202 peripheral blood samples were examined using the single-sample gene set enrichment analysis (ssGSEA) method to detect distinct immune cell types. Hub immune-linked genes in SCZ were identified using the minimal absolute contraction and selection operator analysis. Receptor profiles of central immune-linked genes were analyzed to distinguish the two groups. Finally, the association between immune-linked hub genes and various types of immune cells was assessed. Our findings revealed ten immune cell types and nine key genes involved in SCZ, including effector memory CD4+ T cells, activated CD8+ T cells, mast cells, naive CD8+ T cells, PBMC, type 17 helper cells (Th17), central memory CD8+ T cells, CD56 bright NK cells, memory B cells, and regulatory T cells. Diagnostic models constructed using LASSO regression exhibited an average area under the curve (AUC) of 0.866. Our results indicate immunological dysfunction as a factor in the development of SCZ. ASGR2, ADRM1, AHANK, S100A8, FUCA1, AKNA, GATA3, AHCYL2, and PTRH2 are the key regulatory genes of immune cells, highlighting their potential as novel therapeutic targets for SCZ.

Validity and Cutoff Score of the Autism Mental Status Exam for an Autism Spectrum Disorder Diagnosis in Chinese Children.

The Autism Mental Status exam (AMSE) has demonstrated excellent sensitivity and specificity in Western high-risk population with suspected autism spectrum disorder (ASD). This study aimed to evaluate the psychometric properties of the AMSE in a sample of high-risk Chinese children, and to determine the optimal cutoff score of the Chinese version of the AMSE in supporting ASD diagnosis. 66 young children aged from 2 to 11 years with suspected ASD were enrolled in the present study. A diagnosis of ASD or non-ASD was determined by a Best Estimate Diagnosis protocol according to the DSM-5 criteria. Receiver operating characteristic (ROC) curve analysis was conducted to assess the validity of the AMSE and search for the most effective cutoff score. The ROC curve analysis yields the area under the ROC curve of 0.98 which represents excellent diagnostic accuracy. Findings indicate the optimal cutoff score of the Chinese version of the AMSE was estimated as 6, producing the highest sensitivity of 98% and a specificity of 87%. Preliminary findings of the study suggest the AMSE has promising psychometric properties as an assessment tool for identifying ASD symptoms and supporting diagnostic decision-making in high-risk Chinese children population.

Mobile phone addiction and non-suicidal self-injury among adolescents in China.

Background: Non-suicidal self-injury (NSSI) has recently widely discussed. Independently, mobile phone addiction (MPA) has also attracted academic attention. A few research have examined the correlation between the two. However, there is inadequate knowledge to characterize this relationship altogether. This study further explores the correlation between MPA and NSSI, specifically repeated and severe NSSI. Method: A population-based cross-sectional survey was conducted among 2,719 adolescents in Lincang, Yunnan. The mobile phone addiction index (MPAI) and the Modified Adolescents Self-Harm Survey (MASHS) were administered in combination. The connection between the MPAI and NSSI, as well as both repeated and severe NSSI, was studied using univariate and multivariate logistic regression models. (The copyright holders have permitted the authors to use the MPAI and the MASHS). Results: The prevalence of NSSI was 47.11% (95% CI [36.2-58.0%]), and the detection rate of MPA was 11.11% (95% CI [6.7-18.0%]). The prevalence of NSSI among those with MPA was 4.280 times (95% CI [3.480-5.266]) that of respondents not exhibiting MPA. In addition, all subscales of the MPAI, except for the feeling anxious and lost subscale (FALS), were positively correlated with NSSI. Risk factors, represented by odds ratios, of repeated NSSI with the inability to control cravings subscale (ICCS), the FALS, and the withdrawal and escape subscale (WES) was 1.052 (95% CI [1.032-1.072]), 1.028 (95% CI [1.006-1.051]), and 1.048 (95% CI [1.019-1.078]) respectively. Risk factors of these same three subscales for severe NSSI, had odds ratios of 1.048 (95% CI [1.029-1.068]), 1.033 (95% CI [1.009-1.057]), and 1.045 (95% CI [1.018-1.073]). Conclusion: MPA was shown to be a risk factor for NSSI in adolescents. Individuals with high scores on the ICCS, the WES, and the FALS were more prone to experience repeated and severe NSSI. As a result, early assessment using the MPAI to determine the need for intervention can contribute to the prediction and prevention of NSSI.

Two-stage mental health survey of first-line medical staff after ending COVID-19 epidemic assistance and isolation.

Facing with COVID-19 epidemic such a catastrophic health emergency, the mental health status of medical staff deserves attention. We conducted a two-stage of psychological status monitoring after the end of the assistance and 14 days of isolation, further targeted the vulnerable groups in need of intervention. The study is a cross-sectional survey on 1156 Yunnan medical staff aid to Hubei. Used Cluster sampling method to collect data at 2 time points (at the end of returning from Wuhan and the 14th day of isolation), from March 18, 2020 to April 6, 2020. Female and nurse had higher rates of depressive symptoms than male and doctors and other occupations. The proportion of female with mild and above moderate anxiety levels (22.91%, 2.61%) was higher than male (17.35%, 1.03%) (p < 0.05). Female had a better impaired sleep quality (45.06%, 17.49%) more than male (28.57%, 7.94%). Medical staff supported in Wuhan and with junior professional titles reported a higher proportion of sleep quality impairment. At the 14th isolation day stage, the proportion of nurses changed from depression to health (9.15%) and from health to depression (6.1%) better than doctors. The front-line medical staffs had suffered greater psychological pressure in the treatment process of major public health emergency. Researches on the dynamic monitor for the change of psychological status after aiding epidemic areas were still in relatively blank stage. Targeting the vulnerable characteristics of aiding medical staff is significant for effective psychological intervention and sustainable operation of health system.

Childhood maltreatment and suicidal ideation in Chinese children and adolescents: the mediation of resilience.

BACKGROUND: Childhood maltreatment could increase the risk of suicidal ideation (SI) in adolescents. However, the mediation of resilience in this association remains unclear. METHODS: A population-based cross-sectional study has been done among 3,146 Chinese adolescents. We collected relevant information from the study participants by using self-administered questionnaire. Chinese version of the Childhood Trauma Questionnaire (CTQ), the Resilience Scale for Chinese Adolescents (RSCA), and the Beck Scale for Suicide Ideation (BSSI) were used to measure childhood maltreatment, resilience, and SI, respectively. Univariate and multivariate binary Logistic regression models were employed to estimate crude and adjusted associations between childhood maltreatment, resilience, and SI. Path analysis has subsequently been performed to measure the mediation of resilience in this association. RESULTS: Multivariate Logistic regression models revealed that compared to non-abused counterparts, adolescents who had ever experienced any type of childhood maltreatment was 1.74 times likely to report SI. Among the specific types of childhood maltreatment, emotional abuse showed the strongest association with SI (adjusted OR = 3.01, 95% CI [2.37-3.82]). Path model suggested that over one-third (39.8%) of the total association between childhood maltreatment and SI was mediated via resilience. Emotion regulation and interpersonal assistance were the most prominent mediators among all dimensions of resilience. CONCLUSIONS: Resilience played as a significant mediator in the association between childhood maltreatment and SI. Resilience-oriented intervention measures could be considered for suicidal risk prevention among abused Chinese adolescents.

Psychometric properties of the Caregiver Strain Questionnaire among Chinese parents of children with ADHD or ASD.

BACKGROUND: There is an urgent need in clinical practice to measure the stress of parenting. The Caregiver Strain Questionnaire (CGSQ) was found to be useful to measure parenting stress, but it has not been validated among the Chinese population. AIMS: To assess the reliability and construct validity of the Chinese version of CGSQ among Chinese parents. METHODS: From 2016 to 2017, 266 parents (patient group) with a child having DSM-5-defined attention deficit hyperactivity disorder (ADHD) (n=107) or autism spectrum disorder (ASD) (n=159) and 268 parents of healthy children (control group) were recruited to the present study in Kunming, Yunnan province. All the parents were asked to fill out the Chinese version of CGSQ. We conducted exploratory factor analysis and confirmatory factor analysis (CFA) to verify construct validity of CGSQ in both patient and control groups. Cronbach's α coefficient as an index of internal consistency was assessed for each subscale. Fourteen days later, 23 subjects filled out the scale again. Intra-class correlation coefficient was calculated to evaluate the test-retest reliability. RESULTS: (1) Cronbach's alpha of the global scale was 0.901 for the control group and 0.952 for the patient group. The test-retest reliability for the whole scale was 0.890; (2) CFA indicated that the three-factor model had better fitting indices compared with the two-factor model in both groups. Besides, the fitting indices in the patient group were more favourable than those of the control group, with χ2/df=1.564, Goodness-of-Fit Index=0.841, Comparative Fit Index=0.954, and root mean square error of approximation=0.065 for the patient group at three-factor model; (3) The caregiver strain of ASD parents was statistically higher than that of ADHD parents, and caregiver strain of ADHD parents was higher than that of control group. CONCLUSION: These findings provide initial evidence to support the construct validity and reliability of CGSQ as a parenting stress measurement tool for Chinese parents, especially for parents of children with ADHD or ASD.

Childhood maltreatment with school bullying behaviors in Chinese adolescents: A cross-sectional study.

OBJECTIVE: Although childhood maltreatment and school bullying are common among Chinese adolescents, their possible connection remains severely under-discussed in this population. This study primarily aims to explore the association between childhood maltreatment experience and school bullying behaviors in a large sample of Chinese teenagers. METHOD: A school-based sampling survey was implemented with 2579 adolescents in southwest China. Self-administered questionnaire was used to collect relevant information form the participants. Binary Logistic regression models were adopted to estimate the crude and adjusted associations between childhood maltreatment experience and school bullying involvement in general, as well as between different types of child maltreatment and school bullying. RESULTS: Multivariate Logistic regression models revealed that, for adolescents who had experienced any type of childhood maltreatment, their risk of implicating into school bullying significantly increased (OR=1.75, 95% CI: 1.41-2.16). Further analysis revealed that, for all types of childhood maltreatment and school bullying, only child abuse showed prominent association with bullying victimization: adolescents who reported a history of sexual abuse and emotional abuse were found 4.31 (95% CI: 2.79-6.68) and 2.11 (95% CI: 1.32-3.39) folds of odds for bullying victimization. However, the dose-response association was not apparent between the severity of child abuse and bullying victimization based on subgroup analysis of abused participants. CONCLUSIONS: Childhood maltreatment, especially sexual abuse and emotional abuse, were significantly associated with increased risk of school bullying victimization among Chinese adolescents. Targeted intervention measures should be designed and implemented to protect the abused adolescents from being bullied at school.

Association between parenting and non-suicidal self-injury among adolescents in Yunnan, China: a cross-sectional survey.

BACKGROUND: Non-suicidal self-injury (NSSI) among adolescents is prevalent and its rate has increased in recent years worldwide. Previous studies had investigated the association between parenting and childhood NSSI, but little is known about the relationship between parental rearing and repetition and severity of NSSI. The aim of this study was to investigate associations of parenting with NSSI and its repetition and severity in a representative adolescent sample from southwestern China. METHODS: In this cross-sectional study, a sample of 2,705 adolescents (F/M: 1,245/1,460; mean age: 13.4 ± 2.2 years) was recruited from 14 randomly selected schools in Lincang municipality, Yunnan province, China. A self-report questionnaire was used to collect data. The Adolescent Non-Suicidal Self-Injury Function Assessment Scale and the short Chinese Egna Minnen av Barndoms Uppfostran (s-EMBU-C) were used to evaluate NSSI behaviors and parenting style, respectively. Univariate and multivariate logistic regression models were adopted to examine association between parenting and NSSI. RESULTS: Overall lifetime prevalence of NSSI was 47.1% (95% CI [36.2-58.0]), with self-cutting being the most common form (23.5% (95% CI [19.3-27.7])), followed by hitting hard objects (23.4% (95% CI [20.2-26.7])) and pulling hairs (20.9% (95% CI [18.8-22.6])). In multiple logistic regression analyses, NSSI was positively associated with high level of father's rejection (OR: 1.32 (95% CI [1.01-1.72])), high level of mother's rejection (OR: 1.76 (95% CI [1.46-2.13])), low level of mother's emotional warmth (OR: 1.42 (95% CI [1.15-1.75])), and high level of mother's overprotection (OR: 1.74 (95% CI [1.49-2.03])), repeated NSSI was positively associated with low level of father's emotional warmth (OR: 1.39 (95% CI [1.10-1.75])) and high level of mother's overprotection (OR: 1.79 (95% CI [1.33-2.41])), and severe NSSI was positively associated with low level of father's emotional warmth (OR: 1.64 (95% CI [1.11-2.43])) and high level of mother's rejection (OR: 2.16 (95% CI [1.71-2.71])). CONCLUSION: NSSI is common among adolescents in southwestern China. Negative parenting styles are associated with NSSI, repeated NSSI, and severe NSSI. The development of intervention measures for preventing or reducing NSSI among Chinese adolescents in school settings should consider parenting styles.

Resilience is inversely associated with self-harm behaviors among Chinese adolescents with childhood maltreatment.

BACKGROUND: Abundant studies have identified the association between childhood maltreatment and self-harm (SH), but little has been discussed with regard to the role of resilience in SH behaviors of adolescents who had experienced childhood maltreatment. In this study, we investigated if resilience, as well as its five dimensions, could present negative associations with presence, repetition, and severity of SH among maltreated and neglected adolescents in China. METHODS: A cross-sectional survey including 2,084 maltreated teenagers aged from 10 to 17 years was conducted in southwest China Yunnan province. The Childhood Trauma Questionnaire (CTQ), The Resilience Scale for Chinese Adolescents (RSCA), and the Modified version of Adolescents Self-Harm Scale (MASHS) were adopted to measure childhood maltreatment experiences, psychological resilience, and SH behaviors of the respondents, respectively. Binary univariate and multivariate logistic regression models were employed to discuss the associations between resilience and occurrence, repetition, severity of SH. RESULTS: Among the participants who met the criteria of CTQ, the prevalence rates of SH were 63.83%, 73.94%, 71.50%, 55.53%, and 58.21% for physical abuse (PA), emotional abuse (EA), sexual abuse (SA), physical neglect (PN), and emotional neglect (EN). Final regression model demonstrated that resilience was in general inversely associated with SH, repeated SH, and severe SH for all types of childhood maltreatment, with adjusted odds ratios (aORs) ranging from 0.29 (95% CI: 0.19-0.44) to 0.46 (95% CI: 0.26-0.81). Of the five dimensions of resilience, emotion regulation served as the strongest associated factor of SH among abused youths, regardless of maltreatment types. Besides, compared with those who had lower level of goal concentration and interpersonal assistance, subjects with higher resilience level reported significantly decreased risks of SH occurrence, SH repetition, and more severe SH, in adolescents who had experienced EA and PN. CONCLUSIONS: Resilience showed inverse association with childhood maltreatment related SH in Chinese adolescents. These findings preliminarily indicated that interventions targeting on building up resilience, especially enhancing emotion regulation ability, improving goal concentration, and consolidating interpersonal assistance, could be effective in reducing SH risk, repetition, and severity in maltreated Chinese teenagers.

Resilience mediates the association between school bullying victimization and self-harm in Chinese adolescents.

OBJECTIVE: The association between school bullying and self-harm (SH) in adolescents has been extensively discussed. Nevertheless, little is known about the mechanism of this relationship, particularly the role of resilience. Our research aimed to explore and evaluate the potential moderation and mediation of resilience in the association between school bullying victimization and SH in a large sample of Chinese adolescents. METHOD: We conducted a population-based cross-sectional survey of 3146 adolescents in southwest China. The data were collected by a self-administered questionnaire. Multivariate Logistic regression which incorporated the product term of bullying victimization and resilience was used to estimate the moderation of resilience. Mediation of resilience in bullying victimization and SH were evaluated by path model. RESULTS: The prevalence of bullying involvement and SH were 13.13% (95% CI:9.31%-18.00%) and 47.0% (95% CI: 36.3%-58.0%), respectively. School bullying victimization was positively associated with SH. Resilience was a prominent mediator which accounted for 27.7% of the total association. Among all five dimensions of resilience, emotion regulation (30.90%), interpersonal assistance (24.78%), and family support (22.16%) showed the strongest mediation. Nevertheless, the moderation of resilience in this association was not statistically significant. CONCLUSIONS: The findings of the present study suggest that resilience strengthening measures, particularly those aimed at improving emotion regulation ability and building social support could be effective in reducing school bullying victimization related SH behaviors among Chinese teenagers.

Course, outcome and diagnosis stability of early-onset schizophrenia in Yunnan Province, China-a three years follow-up study.

The aim of the study was to describe diagnostic stability and psychosocial outcomes of subjects with early-onset schizophrenia (EOS). All the subjects who had been hospitalized in the Department of Psychiatry of the First Affiliated Hospital of Kunming Medical University between January 2011 and July 2015 with the diagnosis of International Classification of Diseases (ICD)-10 defined schizophrenia, and discharged from the hospital for more than 12 months were enrolled to the study. The Mini International Neuropsychiatric Interview was applied for life-time ICD -10 diagnoses, and Personal and Social Performance (PSP) for global function evaluation. Altogether 249 patients were targeted for follow-up, in which 101 were followed up and the dropout rate was 59.4%. After average 37.2 ±â€¯16.2 months, 92 patients (including 1 death) were still met the ICD-10 diagnosis of schizophrenia (F20). In terms of global functioning, 48.5% of patients had good outcome, 43.6% had moderate outcome, and 7.9% had poor outcome. A relatively high diagnostic stability of ICD-10 defined schizophrenia was obtained in the current study .Moreover, our results draw a much more optimistic picture of the outcome for EOS than what has previously been reported from Western counties.

DAT1 methylation is associated with methylphenidate response on oppositional and hyperactive-impulsive symptoms in children and adolescents with ADHD.

OBJECTIVES: To examine the association of the DNA methylation of DAT1 and DRD4 gene with methylphenidate (MPH) response in attention deficit hyperactivity disorder (ADHD). METHODS: One hundred and eleven DSM-IV defined ADHD Chinese Han children were recruited. Inattention, hyperactivity-impulsivity and oppositional symptoms were evaluated by the Swanson, Nolan and Pelham-IV-parent rating scale (SNAP-IV-P) at baseline and 6 weeks after MPH treatment. DNA methylation of CpG sites in the promoter sequences of DAT1 and DRD4 was examined for association with treatment response. RESULTS: Greater improvement on the SNAP-IV-P total score and percentage change from baseline score were both significantly correlated with DAT1 methylation (rho =-0.222, P = .019 and rho = -0.203, P = .032, respectively). A secondary analysis demonstrated that the effect of DAT1 methylation on symptom response was primarily related to the percentage change in oppositional symptoms (rho = -0.242; P = .012), with a smaller significant effect on hyperactivity-impulsivity (rho = -0.192; P = .045). No significant correlation was found between the treatment effect on inattention and DAT1 methylation (rho = -0.101; P = .292). No significant correlation was observed between mean DRD4 methylation and measures of treatment outcome or baseline symptoms. CONCLUSIONS: Our findings provide initial evidence for the involvement of the epigenetic alterations of DAT1 in modulating the response to MPH treatment in ADHD, primarily on oppositional and hyperactive-impulsive symptoms.

[Effect of parent training in combination with methylphenidate treatment on family relationships for children with attention deficit/hyperactivity disorder].

OBJECTIVE: To investigate the effect of parent training combined with methylphenidate treatment on family relationships in children with attention deficit/hyperactivity disorder (ADHD). METHODS: Fifty-nine parents of children with ADHD under methylphenidate treatment participated in a modified 5-week training program. The intervention effect was evaluated using the Conners Parent Symptom Questionnaire, ADHD Rating Scale-IV Home Version (ADHD-RS-IV Home Version), Caregiver Strain Questionnaire, Parent-Child Relationship Self-rating Scale and Piers-Harris Children's Self-Concept Scale. Parents also completed the training satisfaction survey before and after the intervention. RESULTS: After the 5-week parent training, compared with the baseline values, total scores of Conners Parent Symptom Questionnaire and scores of conduct problems and anxiety significantly decreased, and scores of attention deficit, hyperactivity, impulsivity and oppositional defiant behaviors of ADHD-RS-IV Home Version, and Caregiver Strain Questionnaire total scores were all significantly decreased (P<0.05), while total scores of the Parent-Child Relationship Self-Rating Scale and Piers-Harris Children's Self-Concept Scale were significantly increased (P<0.05). CONCLUSIONS: Modified 5-week parent training program may improve parent-child relationship and reduce parenting stress in ADHD families.

[Study on attention-deficit hyperactivity disorder in children based on resting-state functional magnetic resonance imaging].

OBJECTIVE: To compare resting-state functional magnetic resonance imaging (fMRI) findings of children with attention-deficit hyperactivity disorder (ADHD) and normal children, and to investigate the possible mechanism of brain dysfunction in children with ADHD. METHODS: Resting-state fMRI was performed on 18 children who met the DSM-IV diagnostic criteria for ADHD (ADHD group) and 18 normal children (control group) matched for age, sex, IQ, degree of education and handedness. The two groups were compared in terms of amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo). RESULTS: Compared with the control group, the ADHD group had decreased ALFF in the bilateral posterior lobes of the cerebellum and the left side of the pons, increased ALFF in the right precentral gyrus, decreased ReHo in the left medial frontal gyrus, right superior frontal gyrus, and left precuneus, and increased ReHo in the left anterior lobe of the cerebellum, left caudate nucleus, right parahippocampal gyrus, left precentral gyrus, and right middle frontal gyrus. CONCLUSIONS: In resting state, children with ADHD have decreased brain activity in some regions, including the cerebellum and frontal cortex, compared with normal children, which supports the hypothesis of dysfunctional fronto-cerebellar circuits in ADHD.