Identifying clinical risk factors correlated with addictive features of non-suicidal self-injury among a consecutive psychiatric outpatient sample of adolescents and young adults.

Non-suicidal self-injury (NSSI) is an issue primarily of concern in adolescents and young adults. Recent literature suggests that persistent, repetitive, and uncontrollable NSSI can be conceptualized as a behavioral addiction. The study aimed to examine the prevalence of NSSI with addictive features and the association of this prevalence with demographic and clinical variables using a cross-sectional and case-control design. A total of 548 outpatients (12 to 22 years old) meeting the criteria for NSSI disorder of DSM-5 were enrolled and completed clinical interviews by 4 psychiatrists. NSSI with addictive features were determined by using a single-factor structure of addictive features items in the Ottawa self-injury inventory (OSI). Current suicidality, psychiatric diagnosis, the OSI, the revised Chinese Internet Addiction Scale, the Childhood Trauma Questionnaire, and the 20-item Toronto Alexithymia Scale were collected. Binary logistic regression analyses were used to explore associations between risk factors and NSSI with addictive features. This study was conducted from April 2021 to May 2022. The mean age of participants was 15.93 (SD = 2.56) years with 418 females (76.3%), and the prevalence of addictive NSSI was 57.5% (n = 315). Subjects with addictive NSSI had a higher lifetime prevalence of nicotine and alcohol use, a higher prevalence of current internet addiction, suicidality, and alexithymia, and were more likely to have physical abuse/neglect, emotional abuse, and sexual abuse than NSSI subjects without addictive features. Among participants with NSSI, the strongest predictors of addictive features of NSSI were female (OR = 2.405, 95% CI 1.512-3.824, p < 0.0001), alcohol use (OR = 2.179, 95% CI 1.378-3.446, p = 0.001), current suicidality (OR = 3.790, 95% CI 2.351-6.109, p < 0.0001), and psysical abuse in childhood (OR = 2.470, 95% CI 1.653-3.690, p < 0.0001). Nearly 3 out of 5 patients (12-22 years old) with NSSI met the criteria of NSSI with addictive features in this psychiatric outpatients sample. Our study demonstrated the importance of the necessity to regularly assess suicide risk, and alcohol use, as well as focus more on females and subjects who had physical abuse in childhood to prevent addictive NSSI.

A multicomponent digital intervention to promote help-seeking for mental health problems and suicide in sexual and gender diverse young adults: A randomized controlled trial.

BACKGROUND: LGBTQ+ community's higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults. METHODS AND FINDINGS: We recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur. CONCLUSIONS: The current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100053248.

NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism.

NCKAP1/NAP1 regulates neuronal cytoskeletal dynamics and is essential for neuronal differentiation in the developing brain. Deleterious variants in NCKAP1 have been identified in individuals with autism spectrum disorder (ASD) and intellectual disability; however, its clinical significance remains unclear. To determine its significance, we assemble genotype and phenotype data for 21 affected individuals from 20 unrelated families with predicted deleterious variants in NCKAP1. This includes 16 individuals with de novo (n = 8), transmitted (n = 6), or inheritance unknown (n = 2) truncating variants, two individuals with structural variants, and three with potentially disruptive de novo missense variants. We report a de novo and ultra-rare deleterious variant burden of NCKAP1 in individuals with neurodevelopmental disorders which needs further replication. ASD or autistic features, language and motor delay, and variable expression of intellectual or learning disability are common clinical features. Among inherited cases, there is evidence of deleterious variants segregating with neuropsychiatric disorders. Based on available human brain transcriptomic data, we show that NCKAP1 is broadly and highly expressed in both prenatal and postnatal periods and demostrate enriched expression in excitatory neurons and radial glias but depleted expression in inhibitory neurons. Mouse in utero electroporation experiments reveal that Nckap1 loss of function promotes neuronal migration during early cortical development. Combined, these data support a role for disruptive NCKAP1 variants in neurodevelopmental delay/autism, possibly by interfering with neuronal migration early in cortical development.

Association between history of miscarriage and autism spectrum disorder.

This case-control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327-3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259-3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939-4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153-4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978-3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534-4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252-2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894-4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus.

Relationship between RELN signaling pathway genes and language development of autism based on a cluster model. / RELNä¿¡å·é€šè·¯åŸºå› ä¸ŽåŸºäºŽèšç±»åˆ†æžæ¨¡åž‹çš„å­¤ç‹¬ç—‡è¯­è¨€å‘è‚²çš„å ³ç³».

OBJECTIVES: Autism is a neurodevelopment disorder with unclear etiology. High heterogeneity is one of the main issues in the etiological studies. This study explores the relationship between RELN signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, CDK5, FYN) and language development of autism patients based on a cluster analysis model which is established to reduce the heterogeneity. METHODS: Autism children were recruited from 5 different medical/autism training institutes from Hunan, Shandong, and Henan provinces, and were divided into 2 parts according to the recruitment time: The first part was the training sample, which was recruited from October 2006 to May 2011, and the second part was the validation sample, which was recruited from July 2011 to May 2012. A two-step cluster analysis was performed to cluster 374 Chinese Han autism patients into different subgroups based on 2 parameters: Onset age of the first word and interval from the first word to the first phase. A Bayes discriminatory equation was established followed the cluster results. Then we used this equation to divide another 310 autism children into prior defined subgroups. After the genotyping data was screened, a single marker case-control association study was conducted. RESULTS: The cluster analysis clustered 374 samples into 3 subgroups. Onset ages of the first word in the Group A were (11.83±4.37) months and intervals from the first word to the first phase were (24.55±8.67) months; onset ages of the first word in the Group B were (12.17±3.46) months, intervals from the first word to the first phase were (7.07±3.79) months; onset ages of the first word of Group C were (30.94±7.60) months, intervals from the first word to the first phase were (4.73±4.80) months. The established equations based on the cluster analysis were YA=-14.442+0.525X1+0.810X2, YB=-4.964+0.477X1+0.264X2, YC=-19.843+1.175X1+0.241X2. Cross validated analysis showed that the false rate of the equation was 3.8%. A total of 341 single nucleotide polymorphism (SNP) in 6 genes passed the quality control. Before divided subgroups, none of these SNPs reached the significant P value (P>2.44×10-5, Bonferroni adjustment). However the result showed that rs1288502 of LRP8 in Group B was significantly different from the control group (P=6.45×10-6). CONCLUSIONS: Based on the cluster analysis of language development, we could establish a discriminatory equation to reduce heterogeneity of autism sample. The association test indicates that LRP8 genein RELN signaling pathway is related to a particular type of language development of autism patients.

Acute Stress Disorder Among Frontline Health Professionals During the COVID-19 Outbreak: A Structural Equation Modeling Investigation.

OBJECTIVE: The outbreak of COVID-19 that commenced in December 2019 in Wuhan, China, has caused extensive public health concerns and posed substantial challenges to health professionals, especially for those in the center of the epidemic. The current study aimed to assess the prevalence, related factors, and mechanism of acute stress disorder (ASD) among health professionals in Wuhan during this critical period. METHODS: The study used a cross-sectional design. Self-administered questionnaires were distributed to the frontline health professionals in Wuhan hospitals from January 28 to February 1, 2020. Mental health-related measurements included ASD, depression, anxiety, conflict experiences, hostility, and psychosomatic symptoms. Structural equation modeling was used to analyze the factors associated with ASD among health professionals. RESULTS: A total of 332 frontline health professionals were included in the analysis (mean [standard deviation] age = 32.21 [8.77] years; 78.0% women). ASD was a prominent mental health problem in the health professionals surveyed, with a prevalence of 38.3%. Anxiety (24.7%) and depression (20.2%) were also common. Structural equation modeling analyses revealed that emotional distress (i.e., anxiety and depressive symptoms) fully mediated the association between conflicts with ASD (the standardized indirect coefficient ß = 0.47, p = .016). The most common reported symptom was chest pain (51.2%). ASD was significantly associated with psychosomatic symptoms. The majority (67.8%) reported being easily annoyed or irritated, and ASD was associated with hostility. CONCLUSIONS: During the COVID-19 outbreak, a substantial number of health professionals in Wuhan suffered from ASD. Furthermore, ASD was found to be associated with psychosomatic symptoms as well as the hostility. The poor mental health of health professionals has detrimental impacts both on the well-being of staff in health care systems and may adversely affect the quality of patient care. We call for interventions that aim to relieve the psychological and occupational stress. Considering that most of our participants were young, female frontline health professionals, the results may not be generalized to more heterogenous samples.

Autism spectrum disorder and severe social impairment associated with elevated plasma interleukin-8.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unclear etiology and pathophysiology. Previous studies have indicated that the dysregulation of cytokines may be involved in the pathogenesis of ASD and that the levels of cytokines may serve as potential biomarkers of this disorder. METHODS: The current study employed a family triad-based case-control design to study the levels of plasma cytokines in families with ASD (n = 45 triads) and controls (n = 38 triads) with a Human Cytokine Twenty-Five-Plex Kit. The Social Responsiveness Scale (SRS) was used to measure social impairment of ASD children. RESULTS: After controlling for the levels of parental cytokines, we identified that interferon-α (IFN-α), interleukin-7 (IL-7), IL-8, IFN-γ-inducible protein-10, and macrophage inflammatory protein-1ß were associated with ASD, and IL-8 was the only cytokine also associated with the levels of both parental cytokines in the offspring-parents regression analysis and three subdomains of SRS (social awareness, cognition, and motivations) in the children with ASD. The receiver operating characteristic curve showed that the log-transformed IL-8 level discriminated children with autism from controls with an area under the curve of 0.858 (95% confidence interval: 0.777-0.939). CONCLUSIONS: Our study suggests that IL-8 is a potential biomarker for ASD and may be involved in the pathogenesis of ASD. IMPACT: The study suggests that IL-8 is a promising biomarker for ASD and may be involved in the pathogenesis of ASD. Only a very few studies have reported the parental cytokine levels. The significant strength of this article is that we applied the family triad-based approach to explore cytokine levels in families with autism and controls. There are no objective biomarkers, making the accurate diagnosis, prognostic prediction and effective treatment difficult, and our study provides promising results.

Parents' and medical staff's experience of adolescents with suicide-related behaviors admitted to a general hospital in China: qualitative study.

BACKGROUND: Currently, there is increasing awareness of suicide-related behaviors. Mental health services are a key location for assisting people with suicide-related behaviors. However, few studies focused on the evaluation and experience of the mental health care system from families and the medical staff's perspective in China. The study aims to explore parents' and the front-line medical staff's experience of an adolescent with suicide-related behaviors admitted to the psychiatry department of a general hospital in China. DESIGN: Qualitative study was employed in the study. Participants were recruited from a general hospital in China characterized by high levels in the Chinese mental health system. METHODS: Semi-structured in-depth interviews were conducted exploring their experience and perceptions when an adolescent was admitted to the hospital. The theme analysis method is used for data analysis. RESULTS: Participants expressed dissatisfaction in the psychiatric department. Other barriers in their work were identified, such as the shortage of staff and difficulties in caring or communicating with patients. Besides, the imperfect treatment system also contributes to the low satisfaction of patients and their families. Two themes and six subthemes were identified: 1) staff perceive patients with SRBs as difficult to engage (feelings of helplessness, the need for compassion, challenges of professional self-efficacy, the recommendations to the health care service); 2) parents not satisfied with the existing hospital services (doubt the hospitalization treatment and the advice to the health care service). CONCLUSION: This study found that insufficient staffing and lacking of systematic professional treatment models are the major challenges. We suggest increasing the input of mental health resources to expand and train the mental health service team and establish a complete set of a treatment model for SRBs.

Counselling and psychotherapy service use in Chinese sexual minority populations: a nationwide survey.

BACKGROUND: This study investigated the prevalence and factors associated with counselling and psychotherapy service use among Chinese sexual minority populations. METHODS: A nationwide cross-sectional study was performed using snowball sampling method, which led to the inclusion of 18,193 participants. Participants' sociodemographic background, clinical, and psychological data were gathered. Multivariate logistic regression analysis was performed to explore any associated factors. RESULTS: There were 2007 participants who had used counselling and psychotherapy service out of the total population. Among those who had used psychotherapy services, 80.2% participants perceived discrimination, 1.1% reported that they had been refused treatment by a counsellor and/or psychotherapist, 1.6% had experienced verbal harassment, and 8.4% reported that their counsellor and/or psychotherapist lacked knowledge and experience in treating sexual minorities. In addition, regression analyses indicated that those who were divorced/widowed, had religious beliefs, and those who had experienced discrimination, verbal harassment, and rejection for treatment by health professionals all had an increased likelihood of utilising counselling and psychotherapy service. CONCLUSIONS: Service providers and policy makers in China should improve the quality and availability of counselling and psychotherapy services to address the mental health needs of sexual minority populations.

Anesthesia, sex and miscarriage history may influence the association between cesarean delivery and autism spectrum disorder.

BACKGROUND: To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association. METHODS: In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD. RESULTS: CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311-1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273-2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392-5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094-4.291; aOR = 2.919, 95% CI = 1.789-4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (ß = - 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD. CONCLUSIONS: The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.

Sleep Problems of Children with Autism May Independently Affect Parental Quality of Life.

The current study explored how and to what extent sleep problems in children with autism spectrum disorder (ASD) impacted their parents' quality of life (QOL). A total of 440 ASD children and 344 age-matched typically developing (TD) children were included in the case-control designed study. In the TD group, a linear regression model showed that the Children's Sleep Habits Questionnaire (CSHQ) total scores were negatively associated with maternal mental health summary (MCS) scores in the SF-36v2 (ß = - 2.831), while in the ASD group, the CSHQ total scores were negatively associated with the parental physical health summary (PCS) scores (ß = - 3.030 for mothers, ß = - 3.651 for fathers). Path analysis showed that sleep problems in ASD children had both direct and indirect effects on maternal PCS scores. The results indicated that sleep problems in children with ASD might affect parental QOL differently from TD children, and act as independent impact factors on parental physical health.

Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.

The genotype-first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype-specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype-to-genotype approach, we performed whole-exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head-size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3) implicated in ASD and related neurodevelopmental disorders. We identify genotype-phenotype correlations for head-size-associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype-to-genotype strategy would accelerate the elucidation of genotype-phenotype relationships for ASD by using phenotype-restricted cohorts.

Mapping out a spectrum of the Chinese public's discrimination toward the LGBT community: results from a national survey.

BACKGROUND: China has the world's largest lesbian, gay, bisexual, and transgender (LGBT) population. This study assessed the discrimination experienced by LGBT individuals in China in a comprehensive way, covering discrimination perpetrated by family, media, medical services, religious communities, schools, social services, and in the workplace. METHODS: The current study involved a national survey of 31 provinces and autonomous regions. Discrimination was measured both in terms of heterosexual participants' attitudes towards LGBT individuals, and LGBT participants' self-perceived discrimination. Pearson correlation analysis was performed to examine the difference between heterosexual participants' attitudes towards LGBT individuals and LGBT participants' self-perceived discrimination. Linear regression was used to investigate the association between gross domestic product per capita and discrimination. RESULTS: Among 29,125 participants, 2066 (7.1%) identified as lesbian, 9491 (32.6%) as gay, 3441 (11.8%) as bisexual, 3195 (11.0%) as transgender, and 10,932 (37.5%) as heterosexual. Heterosexual people were generally friendly towards the LGBT community with a mean score of 21.9 (SD = 2.7, total scale score = 100) and the grand averaged score of self-perceived discrimination by LGBT participants was 49.9 (SD = 2.5). Self-perceived discrimination from family and social services is particularly severe. We created a series of provincial level choropleth maps showing heterosexual participants' acceptance towards the LGBT community, and self-perceived discrimination reported by members of the LGBT community. We found that a higher level of economic development in provinces was associated with a decrease in discrimination, and we identified that every 100 thousand RMB increase in per capita GDP lead to a 6.4% decrease in discriminatory events perpetrated by heterosexuals. CONCLUSIONS: Chinese LGBT groups consistently experience discrimination in various aspects of their daily lives. The prevalence of this discrimination is associated with the economic development of the province in which it occurs. In order to reduce discrimination, it is important for future studies to discover the underlying reasons for discrimination against LGBT individuals in China.

Association between parental body mass index and autism spectrum disorder: a systematic review and meta-analysis.

Studies have examined the association between parental body mass index (BMI) and autism spectrum disorder (ASD) in offspring, with inconsistent results, especially regarding maternal obesity, overweight and underweight. Cochrane Library, EMBASE, PubMed and PsycINFO databases were searched up to March 2018 for relevant observational studies with no language restriction. Our literature search identified 13 eligible studies for meta-analysis (involving 943,293 children and 30,337 cases). For maternal BMI (13 studies), both maternal obesity [OR 1.41 (95% CI 1.19-1.67)] and maternal overweight [OR 1.16 (95% CI 1.05-1.27)] were significantly associated with ASD, while maternal underweight was not associated with ASD [OR 1.08 (95% CI 0.98-1.20)]. For paternal BMI (three studies), no association was found (paternal obesity: OR 1.28, 95% CI 0.94-1.74; overweight: OR 1.07, 95% CI 0.99-1.15; underweight: OR 1.12, 95% CI 0.87-1.44). Pooled estimates were robust in sensitivity analysis and subgroup analyses. Publication bias may exist for studies assessing maternal BMI and ASD risk, but the filled estimates were not altered. Relative to normal weight, maternal obesity and overweight were significantly associated with increased ASD risk, while maternal underweight was not associated with ASD. Although no association between paternal BMI and ASD was found, current evidence is limited (three studies). Future studies are warranted to address more confounding factors and to identify potential mediators of the association, but pre-pregnancy weight control is suggested.

[Metformin treatment of antipsychotic-induced dyslipidemia: analysis of two randomized, placebo-controlled trials].

OBJECTIVE: To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L (P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.

Genotype and phenotype correlations for SHANK3 de novo mutations in neurodevelopmental disorders.

SHANK3 has been identified as the causative gene of 22q13.3 microdeletion syndrome phenotype. De novo mutations (DNMs) of SHANK3 were subsequently identified in patients with several neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia (SCZ), a Rett syndrome-like phenotype, and intellectual disability (ID). Although broad developmental phenotypes of these patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with SHANK3 DNMs. In this study, we identified a de novo splice mutation (NM_033517.1: c.2265+1G>A) that functionally impairs mRNA splicing, produces multiple splice variants, and results in the reduction of the amounts of mRNA. To analyze the genotype and phenotype correlations for SHANK3 DNMs, we reviewed 37 previously published patients with 28 SHANK3 DNMs. Our results revealed that haploinsufficiency of SHANK3 causes a broad spectrum of neurodevelopmental phenotypes with impaired social interaction, repetitive behavior, speech impairment, ID, and regression as the most common observations. Seizures, hypotonia, global development delay, dysmorphic features, and several other features also occurred recurrently. Specific phenotypes are also observed in certain genotypes. Our study provides the frequency of the heterogeneous co-occurring conditions caused by SHANK3 DNMs, which will be beneficial for diagnosis and clinical management.

Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy.

Intermediate phenotype could be used to investigate genetic susceptibility. However, genetic and environmental heterogeneity may interfere with identification of intermediate phenotypes. In this study, we minimized these interferences by using a novel group strategy. A total of 22 drug-naive and first-episode schizophrenia (FES) patients, along with 22 of their kin healthy siblings (HS), 22 non-kin healthy siblings (nHS) of other schizophrenia patients and 22 healthy controls (HC), were recruited. Brain imaging was acquired from the participants. Voxel-based analysis was used to investigate differences in white matter integrity derived from diffusion tensor imaging among the four groups. Two cognitive tests related to our findings were selected to confirm the related phenotypic changes. All of the FES, HS, and nHS groups showed decreased fractional anisotropy (FA) values in the left inferior frontal gyrus (IFG) compared with the HC group (p < 0.05, FDR corrected). The scores of Hopkins Verbal learning Test-Revised and Animal Naming in FES patients were significantly lower than in participants belonging to the other three groups (p < 0.05). Significant correlation between Animal Naming scores and FA values in the left IFG was found in FES patients (r = 0.53, p = 0.01). Moreover, FES patients also showed decreased FA values in the left medial frontal gyrus, left inferior temporal gyrus, left parahippocampal gyrus, left posterior cingulate, and right middle temporal gyrus compared with HC (p < 0.05, FDR corrected). Decreased FA values in the left IFG is a possible intermediate phenotype of schizophrenia, and this finding supports the hypothesis that disrupted connectivity of white matter may be the key substrate of schizophrenia.

Associations among maternal pre-pregnancy body mass index, gestational weight gain and risk of autism in the Han Chinese population.

BACKGROUND: Autism is a neurodevelopmental disorder with an unclear etiology. Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) have been suggested to play a role in the etiology of autism. The current study explores the associations among maternal pre-pregnancy BMI, GWG and the risk of autism in the Han Chinese population. METHODS: Demographic information, a basic medical history and information regarding maternal pre-pregnancy and pregnancy conditions were collected from the parents of 705 Han Chinese children with autism and 2236 unrelated typically developing children. Binary logistic regressions were conducted to calculate the odds ratio (OR) for the relationship among pre-pregnancy BMI, GWG and the occurrence of autism. The interaction between pre-pregnancy BMI and GWG was analyzed by performing stratification analyses using a logistic model. RESULTS: After adjusting for the children's gender, parental age and family annual income, excessive GWG was associated with autism risk in the entire sample (OR = 1.327, 95% CI: 1.021-1.725), whereas the relationship between maternal pre-pregnancy BMI and autism was not significant. According to the stratification analyses, excessive GWG increased the risk of autism in overweight/obese mothers (OR = 2.468, 95% CI: 1.102-5.526) but not in underweight or normal weight mothers. CONCLUSIONS: The maternal pre-pregnancy BMI might not be independently associated with autism risk. However, excessive GWG might increase the autism risk of offspring of overweight and obese mothers.

A comparative study of magnetic resonance imaging on the gray matter and resting-state function in prodromal and first-episode schizophrenia.

It is very difficult to predict the future development possibility of schizophrenia through the clinical symptoms of the high-risk cases. Therefore, how to determine the possibility of developing into schizophrenia individuals before the onset of the diseases are particularly important. The study investigated cerebral gray matter volume differences and resting-state functional connections among patients with psychosis risk syndrome (PRS), patients with first-episode schizophrenic (FES), and healthy controls (HC), aiming to provide scientific clinical evidence for schizophrenia early identification and intervention. A total of 19 PRS patients, 18 FES patients, and 29 HC were recruited. Gray matter volume and amplitude of low-frequency fluctuation (fALFF) during resting-state functional studies were measured. Comparison of gray matter volumes showed that PRS and FES groups had common reduced gray matter volume in the right caudate. PRS and FES patients showed altered connectivity mainly in the semantic processing-related brain areas. fALFF analysis found that PRF and FES patients had significant differences in fALFF values of the brain region mainly located in the subcortical network, visual recognition network, and auditory network. In addition, PRF individuals had a higher fALFF value and a lower fALFF value in the anterior wedge of the cerebral network than the HC group. Gray matter volume loss between related brain areas might appear prior to illness onset. Similar fALFF values occurred in PRS and FES groups indicated that multiple brain regions of neuronal activity abnormalities and unconventional neural network mechanism have been existed in PRS patients.

A novel de novo POGZ mutation in a patient with intellectual disability.

POGZ, the gene encoding pogo transposable element-derived protein with zinc-finger domain, has been implicated in autism spectrum disorder and it is widely expressed in the human tissues, including the brain. Intellectual disability (ID) is highly heterogeneous neurodevelopment disorder and affects ~2-3% of the general population. Here we report the identification of a novel frameshift mutation in the coding region of the POGZ gene (c.1277_1278insC), which occurred de novo in a Chinese patient with ID. In silico analysis and western blotting revealed this frameshift mutation generating truncated protein in peripheral blood lymphocytes, and this may disrupt several important domains of POGZ gene. Our finding broadens the spectrum of POGZ mutations and may help to understand the molecular basis of ID and aid genetic counseling.