Gut microbiome profiles may be related to atypical antipsychotic associated overweight in Asian children with psychiatric disorder: a preliminary study.

Objective: Atypical antipsychotics (APs) modify the gut microbiome, and weight gain in response to AP could be mediated by the gut microbiome. Thus, the present study aimed to explore the changes in the gut bacterial microbiome in AP-exposed children with obesity. Methods: To rule out the confounder of AP indication, the gut bacterial microbiome was compared between healthy controls (Con) and AP-exposed individuals with overweight (APO) or normal weight (APN). Fifty-seven AP-treated outpatients (21 APO and 36 APN) and 25 Con were included in this cross-sectional microbiota study. Results: AP users, regardless of body mass index, exhibited decreased microbial richness and diversity and a distinct metagenomic composition compared to the Con. Although no differences in the microbiota structure were observed between APO and APN groups, the APO group was characterised by a higher abundance of Megamonas and Lachnospira. Additionally, the differences in the microbial functions were observed between APO and APN groups. Conclusions: The gut bacterial microbiota of APO children revealed taxonomic and functional differences compared to Con and APN. Further studies are needed to verify these findings and to explore the temporal and causal relationships between these variables.

Altered gut bacterial-fungal interkingdom networks in children and adolescents with depression.

BACKGROUND: Most studies of the gut-brain axis have focused on bacteria; little is known about commensal fungi. Children and adolescents with depression were reported to have gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been evaluated. METHODS: Faecal samples were obtained from 145 children and adolescents with depression and 110 age- and gender-matched healthy controls. We analysed the fungal microbiota, including in terms of their associations with the gut microbiota, and subjected the internal transcribed spacer 2 (ITS2) rRNA gene to mitochondrial sequencing. RESULTS: Our findings revealed unaltered fungal diversity, but altered taxonomic composition, of the faecal fungal microbiota in the children and adolescents with depression. Key fungi such as Saccharomyces and Apiotrichum were enriched in the depressed patients, while Aspergillus and Xeromyces showed significantly decreased abundance. Interestingly, the bacterial-fungal interkingdom network was markedly altered in the children and adolescents with depression, and mycobiome profiles were associated with different bacterial microbiomes. LIMITATION: The cross-sectional design precluded the establishment of a causal relationship between the gut mycobiota and the children and adolescents with depression. CONCLUSIONS: The gut mycobiome is altered in the children and adolescents with depression. Our findings suggest that fungi play an important role in the balance of the gut microbiota and may help identify novel therapeutic targets for depression.

Exposure to selective noradrenalin reuptake inhibitors during the first trimester of pregnancy and risk of congenital malformations: A meta-analysis of cohort studies.

Selective serotonin-noradrenalin reuptake inhibitors (SNRIs) are used to treat depression and anxiety during pregnancy; however, information regarding their foetal safety is limited. Cohort studies concerning congenital malformations in infants born to mothers exposed to SNRIs during the first trimester of pregnancy were identified. Eight studies were included in the analysis. In general, the use of SNRIs was not associated with an increased risk of overall congenital malformations when compared with no exposure (rate ratio [RR] = 1.07, 95% confidence interval [CI] = 0.94-1.22; P = 0.31), exposure to SSRIs (RR = 1.12, 95% CI = 0.97-1.31; P = 0.12) and no exposure with clinical indication (RR = 1.04, 95% CI = 0.9-1.2; P = 0.564). A significantly increased risk of cardiac malformations was observed (RR = 1.33, 95% CI = 1.15-1.53; P < 0.001); however, this association was not statistically significant when the reference group comprised mothers exposed to SSRIs (RR = 1.1, 95% CI = 0.85-1.43; P = 0.47) or no exposure with clinical indication (RR = 1.17, 95% CI = 0.95-1.42; P = 0.13). The evidence shows no increased risk of congenital malformations and argues against a substantial cardiac teratogenic effect of SNRIs.

Gut microbiota is associated with weight gain in children treated with atypical antipsychotic: A pilot longitudinal study.

We studied longitudinal changes in the microbiome with weight gain during atypical antipsychotics (APs) treatment. 43 inpatients naive to AP paediatric medication were included in the longitudinal microbiota study. The baseline composition of the gut microbiome in the case group was characterised by an increase in Parabacteroides and Eubacterium_hallii_group. During the follow-up, the relative abundances of Romboutsia and Klebsiella increased significantly after 3 months of AP treatment; however, no significant changes in these two gut bacteria were observed in the control group. The baseline composition of the gut microbiome contributed to the risk of AP-associated weight gain.

Fecal microbiota in pediatric depression and its relation to bowel habits.

Although gut microbiota dysbiosis has been observed in the fecal samples of depressive adult patients, the detailed structure and composition of microbiota in pediatric depression remain unclear. To enhance our understanding of gut microbiota structure in depressive children, as well as the relationship between gut microbiota and bowel habits, we performed 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 171 children (101 depressive patients and 70 controls) aged 12-18 years. Further analysis consisting of 30 drug-naive patients and 23 controls was performed to validate the results. Compared to controls, we found markedly decreased microbial richness and diversity, a distinct metagenomic composition with reduced short-chain fatty acid-producing bacteria (associated with healthy status), and overgrowth of bacteria such as Escherichia-Shigella and Flavonifractor in pediatric depression. Further analyses limited to drug-naive patients found similar results. Notably, we also observed that several taxa may be involved in the pathogenesis of disordered bowel habits in pediatric depression. Our findings suggest could inform future pediatric depression interventions specifically targeting the bacteria associated with bowel movements.

Labor epidural analgesia and risk of autism Spectrum disorders in offspring: A systematic review and meta-analysis.

Background: The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent. Methods: We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall relative risk. Results: Our results showed that LEA was associated with an increased risk of ASD in offspring [HR = 1.3, 95% confidence interval (CI): 1.25-1.35; P < 0.001] after combining crude estimates from the included studies. This association was gradually reduced, but still statistically significant, when potential confounding factors were considered (HR 1.13, 95% CI 1.03-1.25, P = 0.014). However, there was no significant association when we combined data of siblings from other pregnancies (HR = 1.07, 95% CI: 0.99-1.16, P = 0.076), implying that the association was due to confounding factors. Conclusion: The statistically significant association between LEA and ASD in the offspring can be partially explained by unmeasured confounding. Systematic Review Registration: Identifier CRD42022302892.

Early Life Antibiotic Exposure and the Subsequent Risk of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

This study was conducted to assess this association between early life antibiotic exposure and the risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in later life. The results showed that early life antibiotic exposure was associated with an increased risk of ASD (OR = 1.13, 95% confidence interval (CI): 1.07-1.21) or ADHD (OR = 1.18, 95% CI: 1.1-1.27). However, this association for ASD (OR = 1.04, 95% CI: 0.97-1.11) or ADHD (OR = 0.98, 95% CI: 0.94-1.02) disappeared when data from sibling-matched studies were pooled. The statistically significant association between early life antibiotic exposure and ASD or ADHD in later life can be partially explained by unmeasured genetic and familial confounding factors.

Maternal infection exposure and the risk of psychosis in the offspring: A systematic review and meta-analysis.

The relationship between maternal infection exposure and the risk of psychosis in the offspring is inconsistent. We systematically assessed this relationship. Unrestricted searches of the PubMed and Embase databases were conducted, with an end date of February 1, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Twenty-three observational studies were included in the analysis. The results showed that mothers who had a history of infection during pregnancy experienced a significantly increased risk of developing psychosis in offspring (OR = 1.25, 95% confidence interval (CI): 1.1-1.41; P = 0.001). Sensitivity and subgroup analyses yielded consistent results. For specific pathogens, the risk of developing psychosis in offspring was increased among mothers with herpes simplex virus 2 (HSV-2) exposure (OR, 1.32; 95% CI, 1.09-1.6; P = 0.004). However, other maternal-specific pathogen exposures were not significantly associated with the risk of psychosis in offspring. No evidence of publication bias was observed. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal infection exposure may be associated with a greater risk of psychosis in the offspring.

Altered gut bacterial-fungal interkingdom networks in patients with current depressive episode.

INTRODUCTION: Bacterial dysbiosis has been described in patients with current depressive episode (CDE); however, the fungal composition in the gut has not been investigated in these patients. METHODS: Here, we characterized the fungal gut mycobiota in patients with CDE. We systematically characterized the microbiota and mycobiota in fecal samples obtained from 24 patients with CDE and 16 healthy controls (HC) using 16S rRNA gene- and ITS1-based DNA sequencing, respectively. RESULTS: In patients with CDE, bacterial dysbiosis was characterized by an altered composition and reduced correlation network density, and the gut mycobiota was characterized by a relative reduction in alpha diversity and altered composition. Most notably, the CDE group had higher levels of Candida and lower level of Penicillium than the HC group. Compared with the HC group, the gut microbiota in patients with CDE displayed a significant disruption in the bacteria-fungi correlation network suggestive of altered interkingdom interactions. Furthermore, a gut microbial index based on the combination of eight genera (four bacterial and four fungal CDE-associated genera) distinguished CDE patients from controls with an area under the curve of approximately 0.84, suggesting that the gut microbiome signature is a promising tool for disease classification. CONCLUSIONS: Our findings suggest that both bacteria and fungi contribute to gut dysbiosis in patients with CDE. Future studies involving larger cohorts and metagenomic or metabolomic analyses may clarify the structure and potential roles and functions of the gut mycobiome and its impact on the development of CDE.

Analysis of gut mycobiota in first-episode, drug-naïve Chinese patients with schizophrenia: A pilot study.

BACKGROUND: Accumulating evidence has focused on elucidating the bacterial component of the gut microbiota in patients with schizophrenia (SC); however, the fungal composition in the gut has not been investigated, although previous studies have suggested that gut mycobiota may be intricately linked to this disorder. The purpose of this analysis was to examine gut bacterial and fungi in first-episode, drug- naïve adult SC patients in relation to age- and sex-matched healthy controls (HC). METHODS: Ten SC patients and 16 HCs were enrolled in this cross-sectional study, and their gut microbiota and mycobiota were systematically characterized using 16S rRNA gene- and ITS1-based DNA sequencing. RESULTS: The microbiota of the SC patients were characterized by increased abundance of harmful bacterial (Proteobacteria) and decreased short-chain fatty acid (SCFA)-producing bacteria, such as the Faecalibacterium and Lachnospiraceae genera. The gut mycobiota were characterized by a relative reduction in alpha diversity and altered composition. Most notably, the SC group had a higher level of Chaetomium and a lower level of Trichoderma than the HC group. Furthermore, the gut microbiota in patients with SC displayed a significant enhancement in the bacteria-fungi correlation network, suggestive of altered interkingdom interactions. CONCLUSIONS: Both the bacterial gut microbiota as well as the gut mycobiota contributed to gut dysbiosis in patients with SC. However, our study was limited by sample size, and additional studies involving larger cohorts characterizing the gut mycobiome in SC patients are needed to form a foundation for research into the relationship between mycobiota, dysbiosis, and SC development.

Infection, antibiotic exposure, and risk of celiac disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta-analysis to investigate this relationship. METHODS: To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: The meta-analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2-1.56; P < 0.001). The I2 was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new-onset CD (odds ratio, 1.2; 95% CI: 1.04-1.39; P < 0.001). CONCLUSION: Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.

Meta-analysis found that studies may have overestimated Caesarean section risks for attention-deficit hyperactivity disorder by ignoring confounding factors.

AIM: Epidemiological studies on associations between Caesarean sections (C-sections) and attention-deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta-analysis. METHODS: We systematically searched PubMed and Embase to December 2018 and included nine hospital-based and population registry studies published in 2011-2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account. RESULTS: We found that that C-sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C-sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C-sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00-1.13, I2 0%), implying that the association was due to confounding. CONCLUSION: The statistically significant association between C-sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.

The prevalence of psychiatric disorders among students aged 6~ 16 years old in central Hunan, China.

BACKGROUND: Though several epidemiological surveys of psychiatric disorders have been carried out in China, only a few of them are concerned about the prevalence of psychiatric disorders in central Hunan and reveal the distribution of common psychiatric disorders and their comorbidities. METHODS: Achenbach's Child Behavior Checklist (CBCL), the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) were administered to a stratified sample of 17,071 participants aged 6 to 16 years old from two cities in the central part of Hunan province. Twelve-month prevalence rates were calculated. RESULTS: Twelve-month prevalence of the population was 9.74%. The most common psychiatric disorders were attention deficit hyperactivity disorder (ADHD) (4.96%), oppositional defiant disorder (ODD) (2.98%) and generalized anxiety disorder (GAD) (1.77%). Of those with a 12-month prevalence diagnosis, 34.6% had one or more comorbid psychiatric disorders. Most notably, ADHD had comorbidity rates of 25.15% with ODD, 18.18% with CD, 6.38% with GAD, and 3.66% with MDD. CONCLUSIONS: Psychiatric disorders are common in Chinese children and adolescents. Being the most prevalent mental disorder, ADHD requires continued focus and support in awareness and education.

Gut microbiota profiles in treatment-naïve children with attention deficit hyperactivity disorder.

BACKGROUNDS: Although increasing evidence suggests a role for the gut microbiota in neurodevelopment, the actual structure and composition of microbiota in children with attention-deficit/hyperactivity disorder (ADHD) remain unclear. METHODS: Thus, the present study aimed to define the characteristics of gut microbiota in treatment-naive children with ADHD and to assess their relationship with the severity of ADHD symptoms. High-throughput pyrosequencing was used to investigate the microbiota composition in fecal matter from 51 children with ADHD and 32 healthy controls (HC). RESULTS: An operational taxonomical unit (OTU)-level analysis revealed a significant decrease in the fractional representation of Faecalibacterium in children with ADHD compared to HC. In individuals with ADHD, the abundance of Faecalibacterium was negatively associated with parental reports of ADHD symptoms. However, there was no significant difference in alpha diversity between the ADHD and control groups. CONCLUSIONS: This present findings support the involvement of microbiota alteration in psychiatric diseases and Faecalibacterium may represent a potential novel marker of gut microbiota in ADHD. Future studies are needed to validate these findings and to elucidate the temporal and causal relationships between these variables.

Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis.

AIM: There is emerging concern that antipsychotics may be associated with an increased risk of myocardial infarction (MI). A previous review identified five observational studies that did not provide an accurate estimate of the association between antipsychotic drug use and MI risk. More recent studies have produced variable results. METHODS: We performed a systematic review and meta-analysis of observational studies to determine whether antipsychotic use affects the risk for MI. Our analysis included all observational studies that compared MI incidence among patients receiving antipsychotics vs. no treatment. RESULTS: Nine observational studies were included in the analysis. The odds for developing MI were 1.88-fold higher (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.39, 2.54) in antipsychotic users compared with individuals who had not taken antipsychotics. Subgroup analyses found an OR of 2.48 (95% CI 1.66, 3.69) among patients with schizophrenia and an OR of 2.64 (95% CI 2.48, 2.81) among short term (<30 days) antipsychotic users. CONCLUSION: The findings of this meta-analysis support an increased risk of MI in antipsychotic drug users. The present systematic review expands previous knowledge by demonstrating an increased and more pronounced risk in short term users.

Broad autism phenotype features of Chinese parents with autistic children and their associations with severity of social impairment in probands.

BACKGROUND: Parents of children with autism have higher rates of broad autism phenotype (BAP) features than parents of typically developing children (TDC) in Western countries. This study was designed to examine the rate of BAP features in parents of children with autism and the relationship between parental BAP and the social impairment of their children in a Chinese sample. METHODS: A total of 299 families with autistic children and 274 families with TDC participated in this study. Parents were assessed using the Broad Autism Phenotype Questionnaire (BAPQ), which includes self-report, informant-report, and best-estimate versions. Children were assessed using the Chinese version of the Social Responsiveness Scale (SRS). RESULTS: Parents of children with autism were significantly more likely to have BAP features than were parents of TDC; mothers and fathers in families with autistic children had various BAP features. The total scores of the informant and best-estimate BAPQ versions for fathers were significantly associated with their children's SRS total scores in the autism group, whereas the total scores of the three BAPQ versions for mothers were significantly associated with their children's SRS total scores in the TDC group. In the autism group, the total SRS scores of children with "BAP present" parents (informant and best-estimate) were higher than the total SRS scores of children with"BAP absent" parents. In the TDC group, the total SRS scores of children with "BAP present" parents were higher than the total SRS scores of children with"BAP absent" parents (best-estimate). CONCLUSIONS: Parents of autistic children were found to have higher rates of BAP than parents of TDC in a sample of Chinese parents. The BAP features of parents are associated with their children's social functioning in both autism families and TDC families, but the patterns of the associations are different.