The interactions between host genome and gut microbiome increase the risk of psychiatric disorders: Mendelian randomization and biological annotation.

BACKGROUND: The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS. METHODS: Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases. RESULTS: METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues. CONCLUSIONS: Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.

Self-rated health as a predictor of hospitalizations in patients with bipolar disorder or major depressive disorder: A prospective cohort study of the UK Biobank.

BACKGROUND: To determine the association between self-rated health (SRH) and subsequent all-cause hospitalizations in patients with bipolar disorder (BD) or major depression (MDD). METHODS: We conducted a prospective cohort study on people with BD or MDD in the UK from 2006 to 2010 using UK Biobank touchscreen questionnaire data and linked administrative health databases. The association between SRH and 2-year all-cause hospitalizations was assessed using proportional hazard regression after adjustment for sociodemographics, lifestyle behaviors, previous hospitalization use, the Elixhauser comorbidity index, and environmental factors. RESULTS: A total of 29,966 participants were identified, experiencing 10,279 hospitalization events. Among the cohort, the average age was 55.88 (SD 8.01) years, 64.02 % were female, and 3029 (10.11 %), 15,972 (53.30 %), 8313 (27.74 %), and 2652 (8.85 %) reported excellent, good, fair, and poor SRH, respectively. Among patients reporting poor SRH, 54.19 % had a hospitalization event within 2 years compared with 22.65 % for those having excellent SRH. In the adjusted analysis, patients with good, fair, and poor SRH had 1.31 (95 % CI 1.21-1.42), 1.82 (95 % CI 1.68-1.98), and 2.45 (95 % CI 2.22, 2.70) higher hazards of hospitalization, respectively, than those with excellent SRH. LIMITATIONS: Selection bias can exist as our cohort cannot fully represent all the BD and MDD cases in the UK. Moreover, the causality is questionable. CONCLUSION: SRH was independently associated with subsequent all-cause hospitalizations in patients with BD or MDD. This large study underscores the need for proactive SRH screening in this population, which might inform resource allocation in clinical care and enhance high-risk population detection.

Automated Digital Interventions and Smoking Cessation: Systematic Review and Meta-analysis Relating Efficiency to a Psychological Theory of Intervention Perspective.

BACKGROUND: Smoking remains a highly significant preventable global public health problem. In this context, digital interventions offer great advantages in terms of a lack of biological side effects, possibility of automatic delivery, and consequent human resource savings relative to traditional interventions. Such interventions have been studied in randomized controlled trials (RCTs) but have not been systematically reviewed with the inclusion of text-based and multiplatform-based interventions. In addition, this area has not been evaluated from the perspective of the psychological theoretical basis of intervention. OBJECTIVE: The aim of this paper is to assess the efficiency of digital interventions in RCT studies of smoking cessation and to evaluate the effectiveness of the strategies used for digital interventions. METHODS: An electronic search of RCTs was conducted using PubMed, Embase, and the Cochrane Library by June 30, 2021. Eligible studies had to compare automated digital intervention (ADI) to the use of a self-help guideline or no intervention. Participants were current smokers (aged 16 years or older). As the main outcome, abstinence after endpoint was extracted from the studies. Systematic review and meta-analysis were conducted to assess the efficiency of ADIs. Metaregressions were conducted to assess the relationship between intervention theory and effectiveness. RESULTS: A total of 19 trials (15,472 participants) were included in the analysis. The overall abstinence rate (95% CI) at the endpoint was 17.8% (17.0-18.7). The overall risk ratio of the intervention group compared to the controls at the endpoint was 17.8% (17.0-18.7). Cochrane risk-of-bias tool for randomized trials (ROB 2) suggested that most of the studies had a low risk of bias (56.3%). Psychological theory-related constructs or predictors, which refer to other theory-based concepts (rather than only behavioral theory) such as craving or anxiety, are associated with effectiveness. CONCLUSIONS: This study found that ADI had a clear positive effect compared to self-help guidelines or to no intervention, and effectiveness was associated with theory-related constructs or predictors. ADIs should be promoted by policy makers and clinical practitioners to address the huge gap between the need for smoking cessation and availability of traditional treatment resources. Possible increases in ADI efficiency may be achieved by optimally integrating psychotherapeutic theories and techniques. TRIAL REGISTRATION: PROSPERO CRD42021256593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=256593.