Nutrition Education in Psychiatry Residency Programs: A Call to Action.

The burden of disease attributable to mental health is expected to rise in the coming decades. Poor nutritional status is considered a modifiable risk factor for general mental health. In fact, nutrition interventions are now accepted as a core strategy in mental healthcare to combat physical health inequalities and life-expectancy gap in people with certain psychiatric disorders. However, most psychiatrists are not familiar with evidence for the potential therapeutic benefits of diet in psychiatric illness, and this may be related to sparse nutrition education for physicians. Thus, there is a need to integrate nutritional management in psychiatric practice, but there is a gap in medical education which would support this practice. Here, we discuss evidence for and challenges in (1) assessing diet quality in psychiatric illness (2) recommending improvements in diet quality and specific dietary patterns in psychiatric illness, and (3) recommending dietary supplements in psychiatric illness. This discussion serves as a call to develop nutrition curricula within psychiatry residency programs.

Identifying the differentially expressed peripheral blood microRNAs in psychiatric disorders: a systematic review and meta-analysis.

Background: Evidence has suggested that microRNAs (miRNAs) may play an important role in the pathogenesis of psychiatric disorders (PDs), but the results remain inconclusive. We aimed to identify specific differentially expressed miRNAs and their overlapping miRNA expression profiles in schizophrenia (SZ), major depression disorder (MDD), and bipolar disorder (BD), the three major PDs. Methods: The literatures up to September 30, 2023 related to peripheral blood miRNAs and PDs were searched and screened from multiple databases. The differences in miRNA levels between groups were illustrated by the standardized mean difference (SMD) and 95% confidence interval (95% CI). Results: In total, 30 peripheral blood miRNAs were included in the meta-analysis, including 16 for SZ, 12 for MDD, and 2 for BD, each was reported in more than 3 independent studies. Compared with the control group, miR-181b-5p, miR-34a-5p, miR-195-5p, miR-30e-5p, miR-7-5p, miR-132-3p, miR-212-3p, miR-206, miR-92a-3p and miR-137-3p were upregulated in SZ, while miR-134-5p, miR-107 and miR-99b-5p were downregulated. In MDD, miR-124-3p, miR-132-3p, miR-139-5p, miR-182-5p, miR-221-3p, miR-34a-5p and miR-93-5p were upregulated, while miR-144-5p and miR-135a-5p were downregulated. However, we failed to identify statistically differentially expressed miRNAs in BD. Interestingly, miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD. Conclusions: Our study identified 13 differentially expressed miRNAs in SZ and 9 in MDD, among which miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD by systematically analyzing qualified studies. These miRNAs may be used as potential biomarkers for the diagnosis of SZ and MDD in the future. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, identifier CRD42023486982.

Decision tree-Markov model of perinatal depression screening: a cost-utility analysis.

Background: Perinatal depression affects the physical and mental health of pregnant women. It also has a negative effect on children, families, and society, and the incidence is high. We constructed a cost-utility analysis model for perinatal depression screening in China and evaluated the model from the perspective of health economics. Methods: We constructed a Markov model that was consistent with the screening strategy for perinatal depression in China, and two screening strategies (screening and non-screening) were constructed. Each strategy was set as a cycle of 3 months, corresponding to the first trimester, second trimester, third trimester, and postpartum. The state outcome parameters required for the model were obtained based on data from the National Prospective Cohort Study on the Mental Health of Chinese Pregnant Women from August 2015 to October 2016. The cost parameters were obtained from a field investigation on costs and screening effects conducted in maternal and child health care institutions in 2020. The cost-utility ratio and incremental cost-utility ratio of different screening strategies were obtained by multiplicative analysis to evaluate the health economic value of the two screening strategies. Finally, deterministic and probabilistic sensitivity analyses were conducted on the uncertain parameters in the model to explore the sensitivity factors that affected the selection of screening strategies. Results: The cost-utility analysis showed that the per capita cost of the screening strategy was 129.54 yuan, 0.85 quality-adjusted life years (QALYs) could be obtained, and the average cost per QALY gained was 152.17 yuan. In the non-screening (routine health care) group, the average cost was 171.80 CNY per person, 0.84 QALYs could be obtained, and the average cost per QALY gained was 205.05 CNY. Using one gross domestic product per capita in 2021 as the willingness to pay threshold, the incremental cost-utility ratio of screening versus no screening (routine health care) was about -3,126.77 yuan, which was lower than one gross domestic product per capita. Therefore, the screening strategy was more cost-effective than no screening (routine health care). Sensitivity analysis was performed by adjusting the parameters in the model, and the results were stable and consistent, which did not affect the choice of the optimal strategy. Conclusion: Compared with no screening (routine health care), the recommended perinatal depression screening strategy in China is cost-effective. In the future, it is necessary to continue to standardize screening and explore different screening modalities and tools suitable for specific regions.

Associations of Mortality Outcomes With Employment Status at Discharge From VA Vocational Rehabilitation Service Programs.

OBJECTIVE: The authors evaluated associations between employment at discharge from Veterans Health Administration Vocational Rehabilitation Service (VR) programs and suicide and other causes of death. METHODS: For veterans receiving VR between October 1, 2005, and September 30, 2014 (N=78,293), proportional hazards analyses were used to test associations of employment with suicide, drug overdose, and external and natural cause mortality rates over 1 and 5 years postdischarge and through December 31, 2019. The analyses were adjusted for clinical and sociodemographic characteristics and propensity for employment. RESULTS: Of the veterans, 94.1% had a psychiatric diagnosis, and 35.5% were employed at VR discharge. In proportional hazards analyses, employment was associated with lower mortality rates through 1 year (suicide, hazard ratio [HR]=0.54; overdose, HR=0.70; external causes, HR=0.62; and natural causes, HR=0.51) and 5 years postdischarge (overdose, HR=0.72; external causes, HR=0.81; and natural causes, HR=0.72). Through December 31, 2019, employment was associated with lower risks for overdose (HR=0.80) and death by external (HR=0.81) and natural (HR=0.80) causes. CONCLUSIONS: Employment at VR discharge was associated with lower mortality risk among veterans with psychiatric diagnoses.

Clinical and sociodemographic characteristics of patients with epilepsy attended at a regional reference psychiatric emergency unit.

OBJECTIVE: Epilepsy is one of the most prevalent chronic neurological diseases, presenting a high frequency of psychiatric disorders (PD). This study sought to evaluate the clinical and sociodemographic profile of patients with epilepsy (PWE) attended at a regional reference psychiatric emergency unit. METHODS: A retrospective, cross-sectional, and descriptive observational study was conducted utilizing a patient record database of individuals with epilepsy who were attended in a regional reference psychiatric emergency unit between January 2018 and August 2022. RESULTS: Out of the 31,800 psychiatric emergency visits, 260 (0.8 %) were of patients with epilepsy (ICD-10: G40). The majority were males (63.5 %) with a mean age of 42.11±15.39 years, single marital status (154; 59.25 %) and elementary education (75; 28.9 %). Most of them (203; 78.1 %) presented at least one psychiatric comorbidity at the emergency visit, but 109 (41.9 %) were not receiving any psychiatric follow-up. A total of 106 patients (40.8 %) had experienced at least one past psychiatric hospitalization. CONCLUSIONS: The occurrence of PD is highly prevalent in PWE, and probably with a high frequency of psychiatric emergencies occurring among them. Further studies are needed to assess such patient profile, particularly involving data from psychiatric emergency units.

Human Brain Magnetic Resonance Imaging Studies for Psychiatric Disorders: The Current Progress and Future Directions.

With the prevalence of psychiatric disorders and the limitations of the diagnostic scheme and treatment options of these disorders, magnetic resonance imaging (MRI) studies play a significant role in uncovering the pathological basis of psychiatric disorders and potentially using biological markers in clinical settings. The use of MRI in clinical research has grown over the past three decades, and current MRI research continues to provide an avenue to guide the development of diagnostic approaches and therapeutic solutions. However, the current shortcomings of MRI studies derive not only from technical limitations (i.e., the range of contrasts that MRI probes or sensors can create) but also from confounding factors in the current methodological approaches of case-control studies for psychiatric disorders. Thus, by reviewing the recent literature on MRI research on psychiatric disorders, we explain the current progress and limitations of brain MRI methodologies used to study psychiatric disorders. We consider the growing use of cross-disorder methods to identify shared and disease-specific pathological features across psychiatric disorders. In addition, we need to outline healthy developmental and aging changes of the brain and investigate the disorder difference as a deviation of the trajectory. Although these methods have provided us with new insights, the demarcation between psychiatric disorders based on a definitive set of pathologies remains limited. This challenge of disease stratification is further complicated by the presence of multiple different sets of disorder pathologies within a single disorder and the different progressive timelines of different disorders. As such, we introduce the ongoing research projects in Japan, namely, the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) and the Strategic International Brain Science Research Promotion Program (Brain/MINDS Beyond). These collaborative research initiatives across Japan use neuroimaging and travel-subject harmonization to conduct nationwide MRI studies capable of providing large-scale coherent results, which may address the current limitations of MRI psychiatric disorder research.

Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the administration of repetitive transcranial magnetic stimulation.

OBJECTIVES: To provide guidance for the optimal administration of repetitive transcranial magnetic stimulation, based on scientific evidence and supplemented by expert clinical consensus. METHODS: Articles and information were sourced from existing guidelines and published literature. The findings were then formulated into consensus-based recommendations and guidance by the authors. The guidelines were subjected to rigorous successive consultation within the RANZCP, involving the Section of ECT and Neurostimulation (SEN) Committee, its broader membership and expert committees. RESULTS: The RANZCP professional practice guidelines (PPG) for the administration of rTMS provide up-to-date advice regarding the use of rTMS in clinical practice. The guidelines are intended for use by psychiatrists and non-psychiatrists engaged in the administration of rTMS to facilitate best practice to optimise outcomes for patients. The guidelines strive to find the appropriate balance between promoting best evidence-based practice and acknowledging that evidence for rTMS use is a continually evolving. CONCLUSION: The guidelines provide up-to-date advice for psychiatrists and non-psychiatrists to promote optimal standards of rTMS practice.

Destination memory disorders: At the junction between memory and socioaffective processing.

The junction between memory dysfunction and socioaffective dysfunction is a complex area as research has typically been interested in one dysfunction rather than in the other. However, this junction can be studied under the lens of destination memory. Destination memory (i.e. the ability to remember to whom a piece of information was previously transmitted) is unique in that it draws on both memory and socioaffective processes. Research has demonstrated how destination memory is prone to distortions in neurological/psychiatric disorders. This paper aims to provide a focused review on the interplay between memory and socioaffective processes in the deterioration of destination memory within these disorders. It shows how both episodic memory and socioaffective dysfunction can jointly contribute to the decline in destination memory, although the contribution of each of the two factors may vary depending on the disorder.

Prevalence of Psychiatric Disorders among Patients with Granulomatosis with Polyangiitis (Wegener's) and the Predictive Role of Personality Traits.

Background: Wegener's disease is an autoimmune condition affecting the respiratory tract and kidneys. Mental health assessment is crucial due to the impact of psychological disorders on the immune system. Despite this, there is limited community-based research on psychiatric disorders and personality traits among patients with Wegener's disease. Objective: This study aimed to investigate the prevalence of psychiatric disorders and examine the predictive role of personality traits among patients with Wegener's disease. Methods: A total of 100 patients met the inclusion and exclusion criteria, and all of them were selected to participate in the study. Out of them, 75 individuals completed the questionnaires. The instruments included the SCL-90 questionnaire and the NEO Big Five personality traits. The data were analysed using Stata software, and the prevalence of psychiatric disorders in different patient groups was determined using the chi-square method. The predictive role of personality traits in mental disorders was examined using multivariate regression. Results: The results revealed that paranoia (53.3%) and depression (44%) had the highest prevalence in terms of psychiatric disorders, while psychosis (17.3%) and hostility (25.33%) had the lowest prevalence. Additionally, the findings demonstrated a positive correlation between most psychiatric disorders and the neuroticism personality trait. Conclusion: Given the influence of mental disorders on the immune system in Wegener's disease, it is essential to provide psychological care for these patients.

Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders.

The nervous and immune systems are highly developed, and each performs specialized physiological functions. However, they work together, and their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, and more general metabolites, are essential for the appropriate regulation of both systems. Tryptophan, an essential amino acid, is converted into functional molecules such as serotonin and kynurenine, both of which play important roles in the nervous and immune systems. The role of kynurenine metabolites in neurodegenerative and psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity of the kynurenine pathway is a critical risk factor for septic shock. In this review, we first outline neuroimmune interactions and tryptophan derivatives and then summarized the changes in tryptophan metabolism in neurological disorders. Finally, we discuss the potential of tryptophan derivatives as therapeutic targets for neuroimmune disorders.

Clinical effectiveness of nirmatrelvir plus ritonavir for patients with COVID-19 and preexisting psychiatric disorders.

OBJECTIVES: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. METHODS: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. RESULTS: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group. CONCLUSION: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

Investigating the shared genetic basis and causal relationships between mucosa-associated lymphoid tissue inflammation and psychiatric disorders.

Background: Chronic and acute inflammation of the mucosa-associated lymphoid tissue have been positively linked to the development of psychiatric disorders in observational studies. However, it remains unclear whether this association is causal. In the present study, we investigated this association, using as proxies genetically predicted tonsillectomy, appendectomy and appendicitis on psychiatric disorders including major depressive disorder (MDD), schizophrenia (SCZ), bipolar depression (BD) and anxiety (ANX) via a two-sample Mendelian randomization (MR) analysis. Methods: Genetic association summary statistics for tonsillectomy, appendectomy and appendicitis were sourced from FinnGen Consortium, comprising data from 342,000 participants. Genetic correlations between all exposures and outcome were calculated with Linkage Disequilibrium Score (LDSC) Regression analysis. MR estimates were then calculated to assess their impact on the risk of developing psychiatric disorders. Sensitivity analysis was employed to test for any directional pleiotropy. Results: Our results suggest that there is no direct causal association between tonsillectomy, appendectomy or appendicitis with a heightened risk for development of psychiatric disorders. The robustness of the results of the main MR analysis was further confirmed with additional sensitivity analyses. However, a moderate inverse genetic correlation was observed between tonsillectomy and MDD traits (rg=-0.39, p-value (P)=7.5x10-5). Conclusion: Our findings provide, for the first time, evidence that there is no causal association between tonsillectomy or appendectomy on subsequent vulnerability of developing psychiatric disorders. Future studies using larger sample size GWAS should focus on unraveling the confounding factors and mediators to investigate this relationship further.

Restless legs symptoms increased during COVID-19 pandemic. International ICOSS-survey.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) has been associated with anxiety, depression, insomnia, lifestyle factors and infections. We aimed to study the prevalence of symptoms of RLS during the COVID-19 pandemic versus pre-pandemic. We hypothesized that pre-existing RLS symptoms worsened and pandemic-related factors may have triggered new symptoms of RLS. METHODS: Adults (≥18 years) from fifteen countries across four continents participated in an online survey between May and August 2020. The harmonized questionnaire included a validated single question on RLS with response alternatives from 1 to 5 on a scale from never to every/almost every evening or night. Other measures were the Insomnia Severity Index (ISI), measures of symptoms of anxiety (GAD-2) and depression (PHQ-2), and questions on different pandemic-related factors. RESULTS: Altogether, 17 846 subjects (63.8 % women) were included in the final analyses. The mean age was 41.4 years (SD 16.1). During the pandemic, symptoms of RLS (≥3 evenings/nights per week) were more common 9.1 % (95 % CI 8.7-10.1) compared to 5.4 % (95 % CI 4.9-6.0) before the pandemic (P < 0.0001). Alltogether 1.3 % (95 % CI 1.1-1.6) respondents had new-onset symptoms (≥3 evenings/nights per week). Moderate-severe insomnia was strongly associated with RLS symptoms. The occurrences of new-onset RLS symptoms were 5.6 % (95 % CI 0.9-13.0) for participants reporting COVID-19 and 1.1 % (95 % CI 0.7-1.5) for non-COVID-19 participants. In the fully adjusted logistic regression model, the occurrence of new-onset RLS symptoms was associated with younger age, social restrictions and insomnia severity. In a similar analysis, RLS symptoms (≥3 evenings/nights per week) were associated with lower education, financial hardship, sleep apnea symptoms, use of hypnotics, insomnia severity, symptoms of depression and possible post-traumatic stress disorder. DISCUSSION: Our findings indicate that RLS symptoms were more common during the pandemic than before. Usually, the prevalence of RLS increases with age. However, during the pandemic, new-onset symptoms of RLS were more common in younger age groups. This may be due to the pandemic-related factors being more pronounced in the younger compared to the older. The association between insomnia, psychiatric symptoms and RLS warrants clinical attention.

A retrospective cohort study of prescription drug use among youth with intellectual/developmental disabilities in British Columbia.

BACKGROUND: People with intellectual/developmental disabilities (IDD) are known to have high rates of prescription drug use, particularly for psychotropic medications. This is of concern due to the many side effects associated with these medications and because of the risks of polypharmacy. In this paper we compare the most commonly dispensed drugs and all psychotropic medications for youth with IDD compared with youth without IDD. METHODS: Using population-level administrative health data over a 10-year period, this study examined medications dispensed to youth with an IDD aged 15-24 years compared with youth without an IDD. The most common medications dispensed and the number of youth they were dispensed to were determined. As well a wide variety of psychotropic medications were examined. RESULTS: There were a total of 20 591 youth with IDD and 1 293 791 youth without IDD identified. Youth with IDD had higher odds of being dispensed pain medications, amoxicillin, salbutamol, levothyroxine and all the psychotropic medications (antidepressants, antipsychotics, anxiolytics, anti-adrenergic agents, mood stabilisers and stimulants). For youth with IDD, 6558 (31.85%) were dispensed two or more different psychotropic medications within a year, compared with 75 963 (5.87%) of youth without IDD. DISCUSSION: Compared to youth without IDD, youth with IDD had significantly higher odds of being dispensed most of the prescription medications studied, including all of the psychotropic medications. They were also twice as likely to be dispensed two or more medications from different classes of psychotropic drugs within the same year. These findings have important implications for the health of people with IDD and for their health care providers.

Applying machine learning to international drug monitoring: classifying cannabis resin collected in Europe using cannabinoid concentrations.

In Europe, concentrations of ∆9-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type). We then tested the ability of machine learning algorithms to classify the type of cannabis resin (either Moroccan-type, or Dutch-type) using routinely collected monitoring data on THC and CBD. Finally, we applied the optimal algorithm to new samples collected in countries where the type of cannabis resin was unknown, the UK and Denmark. Results showed that overall, Dutch-type samples had higher THC (Hedges' g = 2.39) and lower CBD (Hedges' g = 0.81) than Moroccan-type samples. A Support Vector Machine algorithm achieved classification accuracy exceeding 95%, with little variation in this estimate, good interpretability, and plausibility. It made contrasting predictions about the type of cannabis resin collected in the UK (94% Moroccan-type; 6% Dutch-type) and Denmark (36% Moroccan-type; 64% Dutch-type). In conclusion, we provide proof-of-concept evidence for the potential of machine learning to inform international drug monitoring. Our findings should not be interpreted as objective confirmatory evidence but suggest that Dutch-type cannabis resin has higher THC concentrations than Moroccan-type cannabis resin, which may contribute to variation in drug markets and health outcomes for people who use cannabis in Europe.

GPR56, an Adhesion GPCR with Multiple Roles in Human Diseases, Current Status and Future Perspective.

Human G protein-coupled receptor 56 (GPR56) belongs to a member of the adhesion G-protein coupled receptor (aGPCR) family and widely exists in the central nervous system and various types of tumor tissues. Recent studies have shown that abnormal expression or dysfunction of GPR56 is closely associated with many physiological and pathological processes, including brain development, neuropsychiatric disorders, cardiovascular diseases and cancer progression. In addition, GPR56 has been proven to enhance the susceptibility of some antipsychotics and anticarcinogens in response to the treatment of neuropsychological diseases and cancer. Although there have been some reports about the functions of GPR56, the underlying mechanisms implicated in these diseases have not been clarified thoroughly, especially in depression and epilepsy. Therefore, in this review, we described the molecular structure and signal transduction pathway of GPR56 and carried out a comprehensive summary of GPR56's function in the development of psychiatric disorders and cancer. Our review showed that GPR56 deficiency led to depressive-like behaviors and an increase in resistance to antipsychotic treatment. In contrast, the upregulation of GPR56 contributed to tumor cell proliferation and metastasis in malignant diseases such as glioblastoma, colorectal cancer, and ovarian cancer. Moreover, we elucidated specific signaling pathways downstream of GPR56 related to the pathogenesis of these diseases. In summary, our review provides compelling arguments for an attractive therapeutic target of GPR56 in improving the therapeutic efficiency for patients suffering from psychiatric disorders and cancer.

Nutraceuticals in Psychiatric Disorders: A Systematic Review.

Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.

DTNPD: A comprehensive database of drugs and targets for neurological and psychiatric disorders.

In response to the shortcomings in data quality and coverage for neurological and psychiatric disorders (NPDs) in existing comprehensive databases, this paper introduces the DTNPD database, specifically designed for NPDs. DTNPD contains detailed information on 30 NPDs types, 1847 drugs, 514 drug targets, 64 drug combinations, and 61 potential target combinations, forming a network with 2389 drug-target associations. The database is user-friendly, offering open access and downloadable data, which is crucial for network pharmacology studies. The key strength of DTNPD lies in its robust networks of drug and target combinations, as well as drug-target networks, facilitating research and development in the field of NPDs. The development of the DTNPD database marks a significant milestone in understanding and treating NPDs. For accessing the DTNPD database, the primary URL is http://dtnpd.cnsdrug.com, complemented by a mirror site available at http://dtnpd.lyhbio.com.

A comprehensive Mendelian randomization study highlights the relationship between psychiatric disorders and non-tumor gastrointestinal diseases.

Objective: Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear. Methods: We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results. Results: We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320-2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295-1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, p = 0.0157). Conclusion: Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Post-transcriptional dysregulation in autism, schizophrenia, and bipolar disorder.

The alteration of gene expression is not restricted to transcriptional regulation but includes a variety of post-transcriptional mechanisms, however, the role of the latter underlying many diseases remains relatively unknown. By utilizing an RNA-Seq dataset of 1510 brain samples from individuals with autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ), and controls, we assessed the contribution of post-transcriptional dysregulation and identified top perturbators accountable for transcriptomic changes of expression in neuropsychiatric disorders. Around 30% of the variability in expression can be attributed to post-transcriptional dysregulation. Interestingly, RNA stability tended to decrease in SCZ and BD, leading to the inhibition of neurogenesis and neural differentiation, while the increase in ASD, resulted in enhanced activity of apoptosis. This finding implicated contrasting pathologies involving RNA stability among neuropsychiatric disorders. An RNA binding protein (RBP)-ELAVL3 - is predicted to be significantly involved in the disruption of RNA stability in all three disorders. To validate, we knocked down its expression in cerebral organoids. Not only differentially expressed genes in ELAVL3-knockdown covered a considerable proportion of predicted targets in three disorders, we also found neurogenesis was significantly affected, given the diminished proliferation and consequently the reduced size of the organoids. Our study extends the current understanding of the link between post-transcriptional regulation and neuropsychiatric disorders and provides new therapeutic targets for early intervention.