The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the corresponding datasets at the protein complex and functional pathway level. Here, we describe one path forward-an initiative aimed at mapping the physical and genetic interaction networks of these conditions and then using these maps to connect the genomic data to neurobiology and, ultimately, the clinic. These efforts will include a team of geneticists, structural biologists, neurobiologists, systems biologists, and clinicians, leveraging a wide array of experimental approaches and creating a collaborative infrastructure necessary for long-term investigation. This initiative will ultimately intersect with parallel studies that focus on other diseases, as there is a significant overlap with genes implicated in cancer, infectious disease, and congenital heart defects.

Exposure to residential green and blue space and the natural environment is associated with a lower incidence of psychiatric disorders in middle-aged and older adults: findings from the UK Biobank.

BACKGROUND: There is increasing evidence for the role of environmental factors and exposure to the natural environment on a wide range of health outcomes. Whether exposure to green space, blue space, and the natural environment (GBN) is associated with risk of psychiatric disorders in middle-aged and older adults has not been prospectively examined. METHODS: Longitudinal data from the UK biobank was used. At the study baseline (2006-2010), 363,047 participants (women: 53.4%; mean age 56.7 ± 8.1 years) who had not been previously diagnosed with any psychiatric disorder were included. Follow-up was achieved by collecting records from hospitals and death registers. Measurements of green and blue space modeled from land use data and natural environment from Land Cover Map were assigned to the residential address for each participant. Cox proportional hazard models with adjustment for potential confounders were used to explore the longitudinal associations between GBN and any psychiatric disorder and then by specific psychiatric disorders (dementia, substance abuse, psychotic disorder, depression, and anxiety) in middle-aged and older adults. RESULTS: During an average follow-up of 11.5 ± 2.8 years, 49,865 individuals were diagnosed with psychiatric disorders. Compared with the first tertile (lowest) of exposure, blue space at 300 m buffer [hazard ratio (HR): 0.973, 95% confidence interval (CI): 0.952-0.994] and natural environment at 300 m buffer (HR: 0.970, 95% CI: 0.948-0.992) and at 1000 m buffer (HR: 0.975, 95% CI: 0.952-0.999) in the third tertile (highest) were significantly associated with lower risk of incident psychiatric disorders, respectively. The risk of incident dementia was statistically decreased when exposed to the third tertile (highest) of green space and natural environment at 1000 m buffer. The third tertile (highest) of green space at 300 m and 1000 m buffer and natural environment at 300 m and 1000 m buffer was associated with a reduction of 30.0%, 31.8%, 21.7%, and 30.3% in the risk of developing a psychotic disorder, respectively. Subgroup analysis suggested that the elderly, men, and those living with some comorbid conditions may derive greater benefits associated with exposure to GBN. CONCLUSIONS: This study suggests that GBN has significant benefits for lowering the risk of psychiatric disorders in middle-aged and older adults. Future studies are warranted to validate these findings and to understand the potential mechanistic pathways underpinning these novel findings.

Identifying pleiotropic genes for complex phenotypes with summary statistics from a perspective of composite null hypothesis testing.

Pleiotropy has important implication on genetic connection among complex phenotypes and facilitates our understanding of disease etiology. Genome-wide association studies provide an unprecedented opportunity to detect pleiotropic associations; however, efficient pleiotropy test methods are still lacking. We here consider pleiotropy identification from a methodological perspective of high-dimensional composite null hypothesis and propose a powerful gene-based method called MAIUP. MAIUP is constructed based on the traditional intersection-union test with two sets of independent P-values as input and follows a novel idea that was originally proposed under the high-dimensional mediation analysis framework. The key improvement of MAIUP is that it takes the composite null nature of pleiotropy test into account by fitting a three-component mixture null distribution, which can ultimately generate well-calibrated P-values for effective control of family-wise error rate and false discover rate. Another attractive advantage of MAIUP is its ability to effectively address the issue of overlapping subjects commonly encountered in association studies. Simulation studies demonstrate that compared with other methods, only MAIUP can maintain correct type I error control and has higher power across a wide range of scenarios. We apply MAIUP to detect shared associated genes among 14 psychiatric disorders with summary statistics and discover many new pleiotropic genes that are otherwise not identified if failing to account for the issue of composite null hypothesis testing. Functional and enrichment analyses offer additional evidence supporting the validity of these identified pleiotropic genes associated with psychiatric disorders. Overall, MAIUP represents an efficient method for pleiotropy identification.

Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study.

BACKGROUND: Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. METHODS: This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. RESULTS: A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723-3.346, p < 0.001). CONCLUSION: Our findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients' psychological status. Trial registration TSGHIRB No. E202216036.

Characteristics of children with a psychiatric disorder in 1999, 2004 and 2017: an analysis of the national child mental health surveys of England.

BACKGROUND: While research has described the profile of children with poor mental health, little is known about whether this profile and their needs have changed over time. Our aim was to investigate whether levels of difficulties and functional impact faced by children with a psychiatric disorder have changed over time, and whether sociodemographic and family correlates have changed. METHODS: Samples were three national probability surveys undertaken in England in 1999, 2004 and 2017 including children aged 5-15 years. Psychiatric disorders were assessed using the Development and Well-Being Assessment (DAWBA), a standardised multi-informant diagnostic tool based on the tenth International Classification of Diseases (ICD-10). The impact and difficulties of having a disorder (emotional, behavioural or hyperkinetic) were compared over time using total difficulty and impact scores from the Strengths and Difficulties Questionnaire (SDQ). Analyses explored the impact of having any disorder, as well as for each disorder separately. Regression analyses compared associations between disorders and sociodemographic factors over time. RESULTS: Parent- and adolescent-reported total SDQ difficulty and impact scores increased between 1999 and 2017 for children and adolescents with disorders. No differences were noted when using teacher ratings. No differences in total SDQ difficulty score were found for children without a disorder. Comparison of sociodemographic correlates across the surveys over time revealed that ethnic minority status, living in rented accommodation and being in the lowest income quintile had a weaker association with disorder in 2017 compared to 1999. CONCLUSIONS: Our study reveals a concerning trend; children with a disorder in 2017 experienced more severe difficulties and greater impact on functioning at school, home and in their daily lives, compared to children with a disorder in earlier decades. Research is needed to identify and understand factors that may explain the changing nature and level of need among children with a disorder.

Emerging drugs for the treatment of irritability associated with autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient. AREAS COVERED: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action. EXPERT OPINION: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

Disease trajectory of high neuroticism and the relevance to psychiatric disorders: A retro-prospective cohort study.

BACKGROUND: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. METHOD: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome-wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. RESULTS: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety-, depression-, and stress-related disorders. CONCLUSION: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.

Prescription Patterns and Predisposing Factors of Benzodiazepine and Z-Hypnotic Use During Pregnancy: A Nationwide Cohort Study.

PURPOSE: The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy. METHODS: This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods. RESULTS: The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16). CONCLUSIONS: In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy.

MiRNA research-The potential for understanding the multiple facets of anorexia nervosa.

Anorexia nervosa (AN) has a multifaceted and complex pathology, yet major gaps remain in our understanding of factors involved in AN pathology. MicroRNAs (miRNAs) play a regulatory role in translating genes into proteins and help understand and treat diseases. An extensive literature review on miRNAs with AN and comorbidities has uncovered a significant lack in miRNA research. To demonstrate the importance of understanding miRNA deregulation, we surveyed the literature on depression and obesity providing examples of relevant miRNAs. For AN, no miRNA sequencing or array studies have been found, unlike other psychiatric disorders. For depression and obesity, screenings and mechanistic studies were conducted, leading to clinical studies to improve understanding of their regulatory influences. MiRNAs are promising targets for studying AN due to their role as signaling molecules, involvement in psychiatric-metabolic axes, and potential as biomarkers. These characteristics offer valuable insights into the disease's etiology and potential new treatment options. The first miRNA-based treatment for rare metabolic disorders has been approved by the FDA and it is expected that these advancements will increase in the next decade. MiRNA research in AN is essential to examine its role in the development, manifestation, and progression of the disease. PUBLIC SIGNIFICANCE: The current understanding of the development and treatment of AN is insufficient. miRNAs are short regulatory sequences that influence the translation of genes into proteins. They are the subject of research in various diseases, including both metabolic and psychiatric disorders. Studying miRNAs in AN may elucidate their causal and regulatory role, uncover potential biomarkers, and allow for future targeted treatments.

Risk of neuropsychiatric disorders in primary hyperparathyroidism: Parathyroidectomy versus nonoperative management.

BACKGROUND: Neuropsychiatric disorders frequently manifest in primary hyperparathyroidism (PHPT), yet evidence of parathyroidectomy's benefit remains mixed. We sought to compare the incidence of neuropsychiatric disorders among patients treated with parathyroidectomy versus nonoperative management. METHODS: We retrospectively reviewed our institutional administrative database for patients with PHPT. Patients with secondary hyperparathyroidism were excluded. The date of biochemical diagnosis of PHPT was designated as day 0 and new-onset neuropsychiatric disorders were defined as conditions diagnosed after this date. The risk of new-onset neuropsychiatric disorders in propensity score-matched surgical and nonsurgical patients was compared using the Cox regression over a median follow-up of 4.2 years. RESULTS: Our cohort included 3728 patients, predominantly female (78%) and white (63.9%), with a mean (± Standard deviation) age of 62 ± 14 years. Of these, 1704 (45.7%) underwent parathyroidectomy. After propensity score matching and adjusting for clinical characteristics, patients who had parathyroidectomy showed a reduced hazard ratio (HR) for new-onset cognitive impairment (HR: 0.65, 95% CI: 0.47-0.91), somnolence (HR: 0.45, 95% CI: 0.23-0.9) and schizophrenia (HR: 0.08, 95% CI: 0.01-0.6), but not for anxiety (HR: 1.07, 95% CI: 0.83-1.37), depression (HR: 1.02, 95% CI: 0.77-1.36) or suicidal ideation (HR: 0.31, 95% CI: 0.04-2.71). Additionally, surgical patients were less likely to require inpatient care (0.3% vs. 1.8%, p < 0.001) for neuropsychiatric disorders. CONCLUSIONS: Parathyroidectomy is associated with lower risks of new-onset cognitive impairment, schizophrenia, or somnolence, indicating potential benefit of operative management in improving neuropsychiatric symptoms in patients with PHPT.

Psychiatric disorders in older adults with cancer referred to psycho-oncology service in a tertiary care cancer centre: a 7-year real world experience from India.

BACKGROUND: Cancer affects mental health in older adults with cancer (OAC), affecting almost 50% of the patients. There are only a few studies on psychiatric disorders in OAC, especially in low resource settings. We report on our real-world experience of prevalence of and factors associated with psychiatric disorders in OAC referred to a psycho-oncology service in an Indian tertiary care cancer institute. METHODS: We retrospectively analysed medical and psycho-oncology records of patients aged 60 + on cancer-directed treatment or follow-up for < 2 years after treatment completion, referred to psycho-oncology services in a tertiary care cancer centre in Mumbai, India, from Jan 2011-Dec 2017. We recorded sociodemographic, clinical, and treatment-related variables, as well as past psychiatric disorders. The ICD-10 was used to record current psychiatric disorder type and presence. IBM SPSS version 24 (Armonk, NY, USA) was used for descriptive measures, tests of association, and logistic regression analysis. The study protocol was approved by Institutional Ethics Committee and registered with the Clinical Trials Registry-India (CTRI/2020/06/026095). RESULTS: Of 763 patients included in the study, 475 (62.3%) were males and 436 (57.1%) were inpatients, with a median age of 65 years. 93% of the patients had a solid tumour and 207 (27.1%) had a history of psychiatric disorder. A current psychiatric diagnosis was noted in 556 patients (72.9%) on initial presentation, of which adjustment disorders, delirium and depression and anxiety disorders were most frequently seen in 25.2%, 21% and 11.1%, respectively. On univariate analysis, a past history of psychiatric disorders (χ2 = 34.6, p < 0.001), lower performance status (χ2 = 9.9, p = 0.002) and haematolymphoid malignancy (χ2 = 4.08, p = 0.04) significantly increased the risk of current psychiatric diagnosis. Logistic regression confirmed these variables as significant. CONCLUSION: Older adults with cancer referred to psycho-oncology services have high rates of psychiatric disorders at their initial presentation, mainly adjustment disorders, delirium and depression and anxiety. A past history of psychiatric disorders, lower performance status and haematolymphoid cancers significantly increased the risk of psychiatric disorders. Multidisciplinary psycho-oncology teams including a psychiatrist should be integrated in comprehensive care of this group of patients. Further research outcomes and effect of psycho-oncological interventions is required in older adults with cancer in LMIC settings.

Causal relationships between atopic dermatitis and psychiatric disorders: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Observational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety. METHODS: Bidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (Ncases = 60,653, Ncontrols = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method. RESULTS: Bidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy. CONCLUSIONS: Our study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.

Cancer worry and its impact on self-reported depressive symptoms among adult males and females in the US: a nationwide sample study.

OBJECTIVE: With cancer the second deadliest disease in the world, worry about cancer can have mental health or psychiatric implications. This study examines the prevalence, differences, and influence of cancer worry (CW), its interaction effect with age, and other confounders on self-reported depressive symptoms (SRDS) among adult males and females in the US. METHODS: We utilized a nationally representative sample data of 2,950 individuals (males = 1,276; females = 1,674) from Cycle 4 of the Health Information National Trends Survey 5 (HINTS 5) 2020. Using frequencies, bivariate chi-square test, and multivariate logistic regression, we examined the prevalence, difference, and association of CW with SRDS, adjusting for confounders. RESULTS: The prevalence rate of SRDS was found to be 32% among females and 23.5% among males. Among individuals with CW, females had a higher prevalence of SRDS compared to males (40.5% vs. 35.1%). However, there was a significant difference in the likelihood of experiencing SRDS between males and females with CW, with males having 84% increased risk compared to females. Across all age groups, the multivariate analysis of the relationship between CW and SRDS revealed that both males and females showed a significantly decreased likelihood of SRDS compared to those aged 18-34 years. However, males aged 35 years or older exhibited an even more pronounced decrease in likelihood compared to females in the same age group. Nonetheless, when examining the interaction of age and CW, we observed a significantly increased likelihood of SRDS across all age groups. Males, in particular, had a higher increased likelihood of SRDS compared to females across all ages, except for those aged 75 years and older. CONCLUSION: The findings of this study highlight the significant influence of CW on individuals' SRDS and the modifying effect of age, particularly among males. These results are important for a better understanding of the risk of CW on mental health, which can be a preventive strategy or control mechanism.

Post-sepsis psychiatric disorder: Pathophysiology, prevention, and treatment.

Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis, resulting in a marked increase in long-term mortality among affected patients. Regrettably, psychiatric impairment associated with sepsis is frequently disregarded by clinicians. This review aims to summarize recent advancements in the understanding of the pathophysiology, prevention, and treatment of post-sepsis mental disorder, including coronavirus disease 2019-related psychiatric impairment. The pathophysiology of post-sepsis psychiatric disorder is complex and is known to involve blood-brain barrier disruption, overactivation of the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, neurotransmitter dysfunction, programmed cell death, and impaired neuroplasticity. No unified diagnostic criteria for this disorder are currently available; however, screening scales are often applied in its assessment. Modifiable risk factors for psychiatric impairment post-sepsis include the number of experienced traumatic memories, the length of ICU stay, level of albumin, the use of vasopressors or inotropes, daily activity function after sepsis, and the cumulative dose of dobutamine. To contribute to the prevention of post-sepsis psychiatric disorder, it may be beneficial to implement targeted interventions for these modifiable risk factors. Specific therapies for this condition remain scarce. Nevertheless, non-pharmacological approaches, such as comprehensive nursing care, may provide a promising avenue for treating psychiatric disorder following sepsis. In addition, although several therapeutic drugs have shown preliminary efficacy in animal models, further confirmation of their potential is required through follow-up clinical studies.

Identification of novel genomic loci for anxiety symptoms and extensive genetic overlap with psychiatric disorders.

AIMS: Anxiety disorders are prevalent and anxiety symptoms (ANX) co-occur with many psychiatric disorders. We aimed to identify genomic loci associated with ANX, characterize its genetic architecture, and genetic overlap with psychiatric disorders. METHODS: We included a genome-wide association study of ANX (meta-analysis of UK Biobank and Million Veterans Program, n = 301,732), schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), and validated the findings in the Norwegian Mother, Father, and Child Cohort (n = 95,841). We employed the bivariate causal mixture model and local analysis of covariant association to characterize the genetic architecture including overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of loci associated with anxiety and shared with psychiatric disorders. RESULTS: Anxiety was polygenic with 12.9k genetic variants and overlapped extensively with psychiatric disorders (4.1k-11.4k variants) with predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 119 novel loci for anxiety by conditioning on the psychiatric disorders, and loci shared between anxiety and MD n = 47 $$ \left(n=47\right) $$ , BIP n = 33 $$ \left(n=33\right) $$ , SCZ n = 71 $$ \left(n=71\right) $$ , ADHD n = 20 $$ \left(n=20\right) $$ , and ASD n = 5 $$ \left(n=5\right) $$ . Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways including cell adhesion and neurofibrillary tangle compared with genes annotated to the shared loci. CONCLUSIONS: Anxiety is highly polygenic phenotype with extensive genetic overlap with psychiatric disorders, and we identified novel loci for anxiety implicating new molecular pathways. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified molecular underpinnings may lead to potential drug targets.

Impact of the emotional development approach on psychotropic medication in adults with intellectual and developmental disabilities: a retrospective clinical analysis.

BACKGROUND: Compared with the general population, adults with an intellectual developmental disorder (IDD) are more likely to develop mental health problems and to receive high levels of psychotropic medication, particularly antipsychotics. The emotional development (ED) approach may help to better understand the nature of challenging behaviour (CB) and tailor treatment and support accordingly. The aim of this retrospective study was to investigate the impact of the ED approach on the prescription of psychotropic medication during inpatient psychiatric treatment. METHODS: The clinical data of 1758 patients were analysed within a retrospective study design over a period of 12 years. ED level was assessed (1) for the first time (INITIAL-SEO), (2) during a previous hospital stay (PAST-SEO) or (3) not at all (NO-SEO). The effects of the ED assessment and the respective intervention during the current admission on the number of psychotropics and the number and dosage of antipsychotics were analysed for the total sample, including those with CB, autism spectrum disorders and psychosis. Group differences were analysed by a chi-square test and a one-factorial analysis of variance. For analysing the impact of the application of the ED approach on psychotropic medication, a covariance model was applied. Changes between the subsamples were analysed by t-tests for dependent samples. RESULTS: The ED approach had a significant impact on reducing the overall amount of psychotropic medication and the dosage of antipsychotics in all patients with IDD. These effects were mainly attributable to those showing CB. In patients with autism spectrum disorders, the developmental approach reduced the number of antipsychotics. No effects could be observed in patients with psychosis; in this subsample, both the number and dosage of antipsychotics increased. CONCLUSIONS: The application of the ED approach in the current hospital stay reduced the number of psychotropic drugs and the number and dosage of antipsychotics, especially in those patients with IDD and CB, but also in those with autism spectrum disorders.

Child- and parent-related determinants for out-of-home care in a nationwide population with neurodevelopmental disorders: a register-based Finnish birth cohort 1997 study.

Neurodevelopmental disorders (NDDs) are among the most common health issues in childhood and adolescence. Psychiatric disorders are known to be overrepresented among children using child welfare services and placed in out-of-home care (OHC). Child- and parent-related determinants for OHC among a national population with NDDs were evaluated utilising longitudinal register data from the national Finnish Birth Cohort 1997 (n = 58,802) from birth to 18 years (1997-2015). The cohort members with NDDs (n = 5,143, 9% of total cohort) formed our study population. Based on their history of OHC, cohort members with NDD were categorised to OHC (n = 903) and non-OHC groups (n = 4,240). Of all cohort members with NDDs, 17.6% had a history of OHC. Within NDDs, a significant excess of ADHD diagnosis was observed in the OHC group compared to the non-OHC group (49% vs. 26%). The OHC group with NDDs was significantly characterised by having comorbid psychiatric diagnosis for conduct and oppositional disorders (adj. RR 2.21), substance use disorders (adj. RR 1.61) and depression and anxiety disorders (adj. RR 1.60). Of all parent-related determinants, the most prevailing in the OHC group compared to the non-OHC group, was social assistance received by parent (88% vs. 44.5%). The longer the period (in years) for received social assistance, the greater the likelihood for OHC (adj. RRs range from 2.41 for one year to 5.24 for over 4 years). Further, significantly associating determinants for OHC were parental psychiatric disorders (adj. RR 1.42) and parental death (adj. RR 1.23). Our findings from the population-based cohort of children and adolescents with NDDs highlight the importance of screening and assessment of family situation. Also, effective prevention and treating of comorbid psychiatric disorders, especially conduct and oppositional disorders is essential.

Causal links between sedentary behavior, physical activity, and psychiatric disorders: a Mendelian randomization study.

BACKGROUND: Studies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach. METHODS: Potential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran's Q test, the MR-Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis. RESULTS: According to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001-1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914-0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010-0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567-0.912; P = 0.006). CONCLUSION: The study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

Comparing the reliability and validity of youth-reported checklists and standardized interviews for categorical measurement of emotional and behavioral problems.

INTRODUCTION: Self-completed checklists measuring youth mental health problems produce dimensional scale scores and can be converted to categorical classifications representing the presence/absence of psychopathology. We test whether categorical classifications from scale scores are equivalent psychometrically to categorical classifications of the same problems obtained by lay-administered standardized structured diagnostic interviews. METHODS: The sample of n = 325 youth aged 12-18 (44% male) and their parent/caregivers come from combined test-retest reliability studies conducted in Ontario, Canada, from 2011 to 2015. Ontario Child Health Study Emotional Behavioural Scales-Brief Version (OCHS-EBS-B) scores converted to categorical classifications of emotional and behavioral problems were compared with interview classifications. We test hypotheses of statistical equivalence and inferiority, using a confidence interval approach to detect if differences lie within the smallest effect size of interest of ±0.18. We compare categorical classifications on: (1) test-retest reliability (Ò¡), (2) content validity (between-instrument agreement), and (3) construct validity (strength of association with three mental health-related constructs). RESULTS: Average test-retest reliabilities were 0.695 (checklists) and 0.670 (interviews). The reliability of checklist emotional problem classifications was not inferior to interview classifications and the difference in reliability between instruments for behavioral problems was small (-0.036). Average between-instrument agreement was Ò¡ = 0.586 (observed) and Ò¡ = 0.841 (corrected for attenuation due to measurement error) indicating high content overlap. Statistical equivalence criteria were met in 5 of 6 construct validity comparisons. CONCLUSIONS: Categorical classifications of emotional and behavioral problems from youth-reported checklists are, on balance, equivalent to interview classifications. Checklists represent a simple, brief, inexpensive alternative to interviews.

Insights into the Medical Evaluation of Ekbom Syndrome: An Overview.

Ekbom syndrome, also known as delusional parasitosis (DP) or delusional infestation, is an uncommon psychiatric disorder distinguished by an enduring conviction of parasitic infestation, persisting notwithstanding the presence of medical evidence to the contrary. Primarily affecting middle-aged women, DP can manifest either as isolated psychological distress or as a component within a more intricate psychiatric framework, substantially influencing the quality of life for affected individuals. Its pathophysiological mechanism involves uncertain dopaminergic imbalances and dysfunction in the dopamine transporter system. Dermatologists often play a pivotal role in diagnosis, as patients first seek dermatological assessments of their signs and symptoms. However, DP frequently originates from underlying psychiatric disorders or medical variables, manifesting with neurological and infectious causative factors. The diagnostic complexity is attributed to patients' resolute convictions, leading to delayed psychiatric intervention. First-line DP treatment involves antipsychotics, with newer agents demonstrating promising prospects, but the lack of standardized protocols poses a significant therapeutic challenge. In this narrative review, both a comprehensive approach to this uncommon pathology and an update on the state of knowledge in this medical subfield focused on optimizing the management of DP are provided. The complexity of DP underlying its uncommon nature and the incomplete understanding of its pathophysiology highlight the need for further research through multicenter studies and multidisciplinary teams to enhance therapeutic efficacy and safety.