Genomic insights into the shared and distinct genetic architecture of cognitive function and schizophrenia.

Cognitive impairment is a major determinant of functional outcomes in schizophrenia, however, understanding of the biological mechanisms underpinning cognitive dysfunction in the disorder remains incomplete. Here, we apply Genomic Structural Equation Modelling to identify latent cognitive factors capturing genetic liabilities to 12 cognitive traits measured in the UK Biobank. We identified three broad factors that underly the genetic correlations between the cognitive tests. We explore the overlap between latent cognitive factors, schizophrenia, and schizophrenia symptom dimensions using a complementary set of statistical approaches, applied to data from the latest schizophrenia genome-wide association study (Ncase = 53,386, Ncontrol = 77,258) and the Thematically Organised Psychosis study (Ncase = 306, Ncontrol = 1060). Global genetic correlations showed a significant moderate negative genetic correlation between each cognitive factor and schizophrenia. Local genetic correlations implicated unique genomic regions underlying the overlap between schizophrenia and each cognitive factor. We found substantial polygenic overlap between each cognitive factor and schizophrenia and biological annotation of the shared loci implicated gene-sets related to neurodevelopment and neuronal function. Lastly, we show that the common genetic determinants of the latent cognitive factors are not predictive of schizophrenia symptoms in the Norwegian Thematically Organized Psychosis cohort. Overall, these findings inform our understanding of cognitive function in schizophrenia by demonstrating important differences in the shared genetic architecture of schizophrenia and cognitive abilities.

A New Approach for On-Chip Production of Biological Microgels Using Photochemical Cross-Linking.

Photochemical cross-linking is a key step for manufacturing microgels in numerous applications, including drug delivery, tissue engineering, material production, and wound healing. Existing photochemical cross-linking techniques in microfluidic devices rely on UV curing, which can cause cell and DNA damage. We address this challenge by developing a microfluidic workflow for producing microgels using visible light-driven photochemical cross-linking of aqueous droplets dispersed in a continuous oil phase. We report a proof-of-concept to construct microgels from the protein Bovine Serum Albumin (BSA) with [Ru(bpy)3]2+ mediated cross-linking. By controlling the capillary number of the continuous and dispersed phases, the volumetric flow rate, and the photochemical reaction time within the microfluidic tubing, we demonstrate the construction of protein microgels with controllable and uniform dimensions. Our technique can, in principle, be applied to a wide range of different proteins with biological and responsive properties. This work therefore bridges the gap between hydrogel manufacturing using visible light and microfluidic microgel templating, facilitating numerous biomedical applications.

Why Do People Watch Pornography? Cross-Cultural Validation of the Pornography Use Motivations Scale (PUMS) and Its Short Form (PUMS-8).

Motivations for pornography use may vary across gender identities, sexual orientations, and geographical regions, warranting examination to promote individual and public health. The aims of this study were to validate the Pornography Use Motivations Scale (PUMS) in a diverse, multicultural sample, and develop a short form (PUMS-8) that can assess a wide range of pornography use motivations. Using data from 42 countries (N = 75,117; Mage = 32.07; SDage = 12.37), enabled us to thoroughly evaluate the dimensionality, validity, and reliability of the Pornography Use Motivations Scale (PUMS), leading to the development of the more concise PUMS-8 short scale. Additionally, language-, nationality-, gender-, and sexual-orientation-based measurement invariance tests were conducted to test the comparability across groups. Both the PUMS and the PUMS-8 assess eight pornography use motivations, and both demonstrated excellent psychometric properties. Sexual Pleasure emerged as the most frequent motivation for pornography use across countries, genders, and sexual orientations, while differences were observed concerning other motivations (e.g. self-exploration was more prevalent among gender-diverse individuals than men or women). The motivational background of pornography use showed high similarity in the examined countries. Both the PUMS and the PUMS-8 are reliable and valid measurement tools to assess different types of motivations for pornography use across countries, genders, and sexual orientations. Both scales are recommended for use in research and clinical settings.

Exposure to Violence and Mental Health Outcomes Among Pre-schoolers in a South African Birth Cohort.

Little is known about the relationship between violence exposure and mental health in preschoolers living in low- and middle-income countries (LMICs). Multiple regression analyses investigated associations between violence exposure and mental health in the Drakenstein Child Health Study (N = 978), a South African birth cohort. Lifetime violence exposure was assessed at age 4.5 years using the parent-report Child Exposure to Community Violence Checklist (CECV). Mental health was assessed at age 5 years using the Child Behaviour Checklist (CBCL 1.5-5). Eighty-three percent of the children were exposed to some form of violence. Internalising and externalising behaviours were positively associated with overall violence exposure (ß per one unit change in the overall score = 0.55 [0.16, 0.94] and ß = 0.53 [0.23, 0.84], respectively), domestic victimisation (ß per one unit change in the subscore = 1.28 [0.28, 2.27]; ß = 1.14 [0.37, 1.90]) and witnessing community violence (ß = 0.77 [0.15, 1.39]; ß = 0.68 [0.19, 1.18]). There was a positive association between polyvictimisation and externalising (ß = 1.02 [0.30, 1.73]) but not internalising (ß = 0.87 [-0.06, 1.80]) behaviour problems. Evidence for an association of witnessing domestic violence with internalising (ß = 0.63 [-0.97, 2.24]) or externalising (ß = 1.23 [-0.04, 2.50]) behaviours was less robust. There was no association between community victimisation and internalising or externalising behaviours (ß = 0.72 [-1.52, 2.97; ß = 0.68 [ -1.06, 2.41]). Observations highlight the risk for mental health problems among preschoolers living in high-violence contexts and emphasize the need for early interventions.

The Machine Speaks: Conversational AI and the Importance of Effort to Relationships of Meaning.

The focus of debates about conversational artificial intelligence (CAI) has largely been on social and ethical concerns that arise when we speak to machines-what is gained and what is lost when we replace our human interlocutors, including our human therapists, with AI. In this viewpoint, we focus instead on a distinct and growing phenomenon: letting machines speak for us. What is at stake when we replace our own efforts at interpersonal engagement with CAI? The purpose of these technologies is, in part, to remove effort, but effort has enormous value, and in some cases, even intrinsic value. This is true in many realms, but especially in interpersonal relationships. To make an effort for someone, irrespective of what that effort amounts to, often conveys value and meaning in itself. We elaborate on the meaning, worth, and significance that may be lost when we relinquish effort in our interpersonal engagements as well as on the opportunities for self-understanding and growth that we may forsake.

Understanding the impact of congenital infections and perinatal viral exposures on the developing brain using white matter magnetic resonance imaging: a scoping review.

BACKGROUND: Magnetic Resonance Imaging (MRI)-based imaging techniques are useful for assessing white matter (WM) structural and microstructural integrity in the context of infection and inflammation. The purpose of this scoping review was to assess the range of work on the use of WM neuroimaging approaches to understand the impact of congenital and perinatal viral infections or exposures on the developing brain. METHODS: This scoping review was conducted according to the Arksey and O' Malley framework. A literature search was performed in Web of Science, Scopus and PubMed for primary research articles published from database conception up to January 2022. Studies evaluating the use of MRI-based WM imaging techniques in congenital and perinatal viral infections or exposures were included. Results were grouped by age and infection. RESULTS: A total of 826 articles were identified for screening and 28 final articles were included. Congenital and perinatal infections represented in the included studies were cytomegalovirus (CMV) infection (n = 12), human immunodeficiency virus (HIV) infection (n = 11) or exposure (n = 2) or combined (n = 2), and herpes simplex virus (HSV) infection (n = 1). The represented MRI-based WM imaging methods included structural MRI and diffusion-weighted and diffusion tensor MRI (DWI/ DTI). Regions with the most frequently reported diffusion metric group differences included the cerebellar region, corticospinal tract and association fibre WM tracts in both children with HIV infection and children who are HIV-exposed uninfected. In qualitative imaging studies, WM hyperintensities were the most frequently reported brain abnormality in children with CMV infection and children with HSV infection. CONCLUSION: There was evidence that WM imaging techniques can play a role as diagnostic and evaluation tools assessing the impact of congenital infections and perinatal viral exposures on the developing brain. The high sensitivity for identifying WM hyperintensities suggests structural brain MRI is a useful neurodiagnostic modality in assessing children with congenital CMV infection, while the DTI changes associated with HIV suggest metrics such as fractional anisotropy have the potential to be specific markers of subtle impairment or WM damage in neuroHIV.

Structured clinical interview for diagnosing obsessive-compulsive spectrum disorders.

BACKGROUND: There are several established structured diagnostic interviews that cover common mental disorders seen in general psychiatry clinics. The administration of more focused diagnostic interviews may be useful in specialty clinics, such as OCD clinics. A semi-structured clinician-administered interview for obsessive-compulsive spectrum disorders (SCID-OCSD) was developed and adapted for DSM-5/ICD-11 obsessive-compulsive and related disorders as well as other putative obsessive-compulsive spectrum conditions. OBJECTIVE: To introduce a semi-structured diagnostic interview for in-depth assessment of obsessive-compulsive spectrum disorders (OCSDs), and to report on its implementation in adults with primary OCD attending an OCD-specialized unit. METHODS: Patients with primary OCD were interviewed using the SCID-OCSD. The SCID-OCSD assesses disorders drawn from several diagnostic categories that share some core features of obsessive-compulsive phenomenology and that are often comorbid in OCD (e.g., obsessive-compulsive related disorders, impulse-control disorders, and a spectrum of compulsive-impulsive conditions such as tics, eating disorders, non-suicidal self-injury, and behavioral addictions. Participants had to be at least moderately symptomatic on the Yale-Brown Obsessive-Compulsive Severity scale (YBOCS, i.e., a total score ≥ 14) to be included in the current study. RESULTS: One hundred and one adult patients with current OCD (n = 101, 37 men and 64 women), took part in the study. Forty-two participants (n = 42) had OCD and one or more current or past comorbid OCSDs, with excoriation (skin-picking) disorder (n = 16) and body dysmorphic disorder (n = 14) being the most common. Nine (n = 9) participants reported a history of non-suicidal self-injury, and 6 participants reported a history of comorbid tics. CONCLUSIONS: In OCD clinics, the SCID-OCSD may help diagnose the full range of putative OCSDs, and so facilitate treatment planning and research on these conditions.

Persistent Impact of Antenatal Maternal Anaemia on Child Brain Structure at 6-7 Years of Age: A South African Child Health Study.

Background: The study aim was to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, putamen, and caudate nucleus volumes previously described in children at age 2-3 years persist to age 6-7 years in the Drakenstein Child Health Study (DCHS). Methods: This neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin<11g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia. Results: Overall, 157 children (Mean [SD] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85% (50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference, -6.77%; p=0.003), left caudate nucleus (adjusted percentage difference, -5.98%, p=0.005), and right caudate nucleus (adjusted percentage difference, -6.12%; p=0.003). Continuous maternal haemoglobin was positively associated with total corpus callosum (ß=0.239 [CI: 0.10 to 0.38]; p<0.001) and caudate nucleus (ß=0.165 [CI: 0.02 to 0.31]; p=0.027) volumes. In a sub-group (n=89) with child haemoglobin data (Mean [SD] age of 76.06[4.84]), the prevalence of antenatal maternal anaemia and postnatal child anaemia was 38.20% (34/89) and 47.19% (42/89), respectively. There was no association between maternal and child anaemia (c2 = 0.799; p=0.372), and child anaemia did not contribute to regional brain volume differences associated with maternal anaemia. Conclusions: Associations between maternal anaemia and regional child brain volumes previously reported at 2-3 years of age were consistent and persisted to 6-7 years of age. Findings support the importance of optimizing antenatal maternal health and reinforce these brain regions as a future research focus on intervention outcomes.

Comparative effectiveness of remote digital gamified and group CBT skills training interventions for anxiety and depression among college students: Results of a three-arm randomised controlled trial.

Digital interventions can enhance access to healthcare in under-resourced settings. However, guided digital interventions may be costly for low- and middle-income countries, despite their effectiveness. In this randomised control trial, we evaluated the effectiveness of two digital interventions designed to address this issue: (1) a Cognitive Behavioral Therapy Skills Training (CST) intervention that increased scalability by using remote online group administration; and (2) the SuperBetter gamified self-guided CBT skills training app, which uses other participants rather than paid staff as guides. The study was implemented among anxious and/or depressed South African undergraduates (n = 371) randomised with equal allocation to Remote Group CST, SuperBetter, or a MoodFlow mood monitoring control. Symptoms were assessed with the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Intention-to-treat analysis found effect sizes at the high end of prior digital intervention trials, including significantly higher adjusted risk differences (ARD; primary outcome) in joint anxiety/depression remission at 3-months and 6-months for Remote Group CST (ARD = 23.3-18.9%, p = 0.001-0.035) and SuperBetter (ARD = 12.7-22.2%, p = 0.047-0.006) than MoodFlow and mean combined PHQ-9/GAD-7 scores (secondary outcome) significantly lower for Remote Group CST and SuperBetter than MoodFlow. These results illustrate how innovative delivery methods can increase the scalability of standard one-on-one guided digital interventions. PREREGISTRATION INTERNATIONAL STANDARD RANDOMISED CONTROLLED TRIAL NUMBER (ISRTCN) SUBMISSION #: 47,089,643.

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.

The short version of the Sexual Distress Scale (SDS-3): Measurement invariance across countries, gender identities, and sexual orientations.

Background: The three-item Sexual Distress Scale (SDS-3) has been frequently used to assess distress related to sexuality in public health surveys and research on sexual wellbeing. However, its psychometric properties and measurement invariance across cultural, gender and sexual subgroups have not yet been examined. This multinational study aimed to validate the SDS-3 and test its psychometric properties, including measurement invariance across language, country, gender identity, and sexual orientation groups. Methods: We used global survey data from 82,243 individuals (Mean age=32.39 years; 40.3 % men, 57.0 % women, 2.8 % non-binary, and 0.6 % other genders) participating in the International Sexual Survey (ISS; https://internationalsexsurvey.org/) across 42 countries and 26 languages. Participants completed the SDS-3, as well as questions regarding sociodemographic characteristics, including gender identity and sexual orientation. Results: Confirmatory factor analysis (CFA) supported a unidimensional factor structure for the SDS-3, and multi-group CFA (MGCFA) suggested that this factor structure was invariant across countries, languages, gender identities, and sexual orientations. Cronbach's α for the unidimensional score was 0.83 (range between 0.76 and 0.89), and McDonald's ω was 0.84 (range between 0.76 and 0.90). Participants who did not experience sexual problems had significantly lower SDS-3 total scores (M = 2.99; SD=2.54) compared to those who reported sexual problems (M = 5.60; SD=3.00), with a large effect size (Cohen's d = 1.01 [95 % CI=-1.03, -0.98]; p < 0.001). Conclusion: The SDS-3 has a unidimensional factor structure and appears to be valid and reliable for measuring sexual distress among individuals from different countries, gender identities, and sexual orientations.

Clozapine Efficacy and Adverse Drug Reactions Among a Nationwide Study of 1021 Australians Prescribed Clozapine: The ClozaGene Study.

BACKGROUND AND HYPOTHESIS: The ClozaGene Study is a nationwide cohort of adults who have been treated with clozapine. While clozapine is indicated in the management of treatment-resistant schizophrenia, it is associated with a considerable adverse drug reaction (ADR) burden, and not all patients achieve adequate symptomatic response. The current study focuses on self-reported experiences of clozapine use and response, clozapine-associated ADRs, and mental health comorbidity. STUDY DESIGN: A total of 1021 participants (41.0% female; aged 46.2 ±â€…10.6 years [range 18-66]) were recruited via a mail-out based on prescriptions for clozapine. Participants completed a self-report questionnaire. STUDY RESULTS: Most participants (90.1%, n = 912) were living with schizophrenia while 41.5% reported a lifetime diagnosis of depression, 15.6% bipolar disorder, and 8.1% schizoaffective disorder. Clozapine was currently prescribed to 944 (92.5%) participants and 37.8% of these participants self-reported currently taking additional antipsychotic medication. Nearly 3 quarters of participants living with schizophrenia reported that clozapine helped control their schizophrenia symptoms moderately to very well. The most commonly reported ADRs were sialorrhea (80.3%), weight gain (71.0%), constipation (56.9%), and sedation (52.8%). The prevalence of clozapine cessation due to clozapine-induced myocarditis and neutropenia was 1% and 0.4%, respectively. CONCLUSIONS: Our findings highlight the high rate of psychotic and metabolic symptoms and ADRs among adults prescribed clozapine in the general Australian population. Future genomic analyses will focus on identifying genetic variants influencing clozapine treatment response and side effects.

Damage to tropical forests caused by cyclones is driven by wind speed but mediated by topographical exposure and tree characteristics.

Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world.

Time-resolved surface reaction kinetics in the pressure gap.

We extend the use of our recently developed Near-Ambient Pressure Velocity Map Imaging (NAP-VMI) technique to study the kinetics and dynamics of catalytic reactions in the pressure gap. As an example, we show that NAP-VMI combined with molecular beam surface scattering allows the direct measurement of time- and velocity-resolved kinetics of the scattering and oxidation of CO on the Pd(110) surface with oxygen pressures at the surface up to 1 × 10-5 mbar, where different metastable surface structures form. Our results show that the c(2 × 4) oxide structure formed at low O2 pressure is highly active for CO oxidation. The velocity distribution of the CO2 products shows the presence of two reaction channels, which we attribute to reactions starting from two distinct but rapidly interconverting CO binding sites. The effective CO oxidation reaction activation energy is Er = (1.0 ± 0.13) eV. The CO2 production is suppressed at higher O2 pressure due to the number of antiphase domain boundaries increasing, and the missing row sites are filled by O-atoms at O2 pressures approaching 1 × 10-6 mbar. Filling of these sites by O-atoms reduces the CO surface lifetime, meaning the surface oxide is inactive for CO oxidation. We briefly outline further developments planned for the NAP-VMI and its application to other types of experiments.

Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms.

BACKGROUND: Acute traumatic stress symptoms may develop in people who have been exposed to a traumatic event. Although they are usually self-limiting in time, some people develop post-traumatic stress disorder (PTSD), a severe and debilitating condition. Pharmacological interventions have been proposed for acute symptoms to act as an indicated prevention measure for PTSD development. As many individuals will spontaneously remit, these interventions should balance efficacy and tolerability. OBJECTIVES: To assess the efficacy and acceptability of early pharmacological interventions for prevention of PTSD in adults experiencing acute traumatic stress symptoms. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase and two other databases. We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 23 January 2023. SELECTION CRITERIA: We included randomised controlled trials on adults exposed to any kind of traumatic event and presenting acute traumatic stress symptoms, without restriction on their severity. We considered comparisons of any medication with placebo, or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Using a random-effects model, we analysed dichotomous data as risk ratios (RR) and calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). Our primary outcomes were PTSD severity and dropouts due to adverse events. Secondary outcomes included PTSD rate, functional disability and quality of life. MAIN RESULTS: We included eight studies that considered four interventions (escitalopram, hydrocortisone, intranasal oxytocin, temazepam) and involved a total of 779 participants. The largest trial contributed 353 participants and the next largest, 120 and 118 participants respectively. The trials enrolled participants admitted to trauma centres or emergency departments. The risk of bias in the included studies was generally low except for attrition rate, which we rated as high-risk. We could meta-analyse data for two comparisons: escitalopram versus placebo (but limited to secondary outcomes) and hydrocortisone versus placebo. One study compared escitalopram to placebo at our primary time point of three months after the traumatic event. There was inconclusive evidence of any difference in terms of PTSD severity (mean difference (MD) on the Clinician-Administered PTSD Scale (CAPS, score range 0 to 136) -11.35, 95% confidence interval (CI) -24.56 to 1.86; 1 study, 23 participants; very low-certainty evidence), dropouts due to adverse events (no participant left the study early due to adverse events; 1 study, 31 participants; very low-certainty evidence) and PTSD rates (RR 0.59, 95% CI 0.03 to 13.08; NNTB 37, 95% CI NNTB 15 to NNTH 1; 1 study, 23 participants; very low-certainty evidence). The study did not assess functional disability or quality of life. Three studies compared hydrocortisone to placebo at our primary time point of three months after the traumatic event. We found inconclusive evidence on whether hydrocortisone was more effective in reducing the severity of PTSD symptoms compared to placebo (MD on CAPS -7.53, 95% CI -25.20 to 10.13; I2 = 85%; 3 studies, 136 participants; very low-certainty evidence) and whether it reduced the risk of developing PTSD (RR 0.47, 95% CI 0.09 to 2.38; NNTB 14, 95% CI NNTB 8 to NNTH 5; I2 = 36%; 3 studies, 136 participants; very low-certainty evidence). Evidence on the risk of dropping out due to adverse events is inconclusive (RR 3.19, 95% CI 0.13 to 75.43; 2 studies, 182 participants; low-certainty evidence) and it is unclear whether hydrocortisone might improve quality of life (MD on the SF-36 (score range 0 to 136, higher is better) 19.70, 95% CI -1.10 to 40.50; 1 study, 43 participants; very low-certainty evidence). No study assessed functional disability. AUTHORS' CONCLUSIONS: This review provides uncertain evidence regarding the use of escitalopram, hydrocortisone, intranasal oxytocin and temazepam for people with acute stress symptoms. It is therefore unclear whether these pharmacological interventions exert a positive or negative effect in this population. It is important to note that acute traumatic stress symptoms are often limited in time, and that the lack of data prevents the careful assessment of expected benefits against side effects that is therefore required. To yield stronger conclusions regarding both positive and negative outcomes, larger sample sizes are required. A common operational framework of criteria for inclusion and baseline assessment might help in better understanding who, if anyone, benefits from an intervention. As symptom severity alone does not provide the full picture of the impact of exposure to trauma, assessment of quality of life and functional impairment would provide a more comprehensive picture of the effects of the interventions. The assessment and reporting of side effects may facilitate a more comprehensive understanding of tolerability.

Cross-cultural equivalence of the Kessler Psychological Distress Scale (K10) across four African countries in a multi-national study of adults.

The Kessler Psychological Distress Scale (K10) has been widely used to screen psychological distress across many countries. However, its performance has not been extensively studied in Africa. The present study sought to evaluate and compare measurement properties of the K10 across four African countries: Ethiopia, Kenya, Uganda, and South Africa. Our hypothesis is that the measure will show equivalence across all. Data are drawn from a neuropsychiatric genetic study among adult participants (N = 9179) from general medical settings in Ethiopia (n = 1928), Kenya (n = 2556), Uganda (n = 2104), and South Africa (n = 2591). A unidimensional model with correlated errors was tested for equivalence across study countries using confirmatory factor analyses and the alignment optimization method. Results displayed 30 % noninvariance (i.e., variation) for both intercepts and factor loadings across all countries. Monte Carlo simulations showed a correlation of 0.998, a good replication of population values, indicating minimal noninvariance, or variation. Items "so nervous," "lack of energy/effortful tasks," and "tired" were consistently equivalent for intercepts and factor loadings, respectively. However, items "depressed" and "so depressed" consistently differed across study countries (R2 = 0) for intercepts and factor loadings for both items. The K10 scale likely functions equivalently across the four countries for most items, except "depressed" and "so depressed." Differences in K10 items were more common in Kenya and Ethiopia, suggesting cultural context may influence the interpretation of some items and the potential need for cultural adaptations in these countries.

Philosophy of psychiatry: theoretical advances and clinical implications.

Work at the intersection of philosophy and psychiatry has an extensive and influential history, and has received increased attention recently, with the emergence of professional associations and a growing literature. In this paper, we review key advances in work on philosophy and psychiatry, and their related clinical implications. First, in understanding and categorizing mental disorder, both naturalist and normativist considerations are now viewed as important - psychiatric constructs necessitate a consideration of both facts and values. At a conceptual level, this integrative view encourages moving away from strict scientism to soft naturalism, while in clinical practice this facilitates both evidence-based and values-based mental health care. Second, in considering the nature of psychiatric science, there is now increasing emphasis on a pluralist approach, including ontological, explanatory and value pluralism. Conceptually, a pluralist approach acknowledges the multi-level causal interactions that give rise to psychopathology, while clinically it emphasizes the importance of a broad range of "difference-makers", as well as a consideration of "lived experience" in both research and practice. Third, in considering a range of questions about the brain-mind, and how both somatic and psychic factors contribute to the development and maintenance of mental disorders, conceptual and empirical work on embodied cognition provides an increasingly valuable approach. Viewing the brain-mind as embodied, embedded and enactive offers a conceptual approach to the mind-body problem that facilitates the clinical integration of advances in both cognitive-affective neuroscience and phenomenological psychopathology.

SEMA3B inhibits TGFß-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF.

Idiopathic pulmonary fibrosis (IPF) is marked by the activation of fibroblasts, leading to excessive production and deposition of extracellular matrix (ECM) within the lung parenchyma. Despite the pivotal role of ECM overexpression in IPF, potential negative regulators of ECM production in fibroblasts have yet to be identified. Semaphorin class 3B (SEMA3B), a secreted protein highly expressed in lung tissues, has established roles in axonal guidance and tumor suppression. However, the role of SEMA3B in ECM production by fibroblasts in the pathogenesis of IPF remains unexplored. Here, we show the downregulation of SEMA3B and its cognate binding receptor, neuropilin 1 (NRP1), in IPF lungs compared with healthy controls. Notably, the reduced expression of SEMA3B and NRP1 is associated with a decline in lung function in IPF. The downregulation of SEMA3B and NRP1 transcripts was validated in the lung tissues of patients with IPF, and two alternative mouse models of pulmonary fibrosis. In addition, we show that transforming growth factor-ß (TGFß) functions as a negative regulator of SEMA3B and NRP1 expression in lung fibroblasts. Furthermore, we demonstrate the antifibrotic effects of SEMA3B against TGFß-induced ECM production in IPF lung fibroblasts. Overall, our findings uncovered a novel role of SEMA3B in the pathogenesis of pulmonary fibrosis and provided novel insights into modulating the SEMA3B-NRP1 axis to attenuate pulmonary fibrosis.NEW & NOTEWORTHY The excessive production and secretion of collagens and other extracellular matrix proteins by fibroblasts lead to the scarring of the lung in severe fibrotic lung diseases. This study unveils an antifibrotic role for semaphorin class 3B (SEMA3B) in the pathogenesis of idiopathic pulmonary fibrosis. SEMA3B functions as an inhibitor of transforming growth factor-ß-driven fibroblast activation and reduced levels of SEMA3B and its receptor, neuropilin 1, are associated with decreased lung function in idiopathic pulmonary fibrosis.

Joint effects of prenatal exposure to indoor air pollution and psychosocial factors on early life inflammation.

It is hypothesized that air pollution and stress impact the central nervous system through neuroinflammatory pathways Despite this, the association between prenatal exposure to indoor air pollution and psychosocial factors on inflammatory markers in infancy has been underexplored in epidemiology studies. This study investigates the individual and joint effects of prenatal exposure to indoor air pollution and psychosocial factors on early life inflammation (interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). We analyzed data from the South African Drakenstein Child Health Study (N = 225). Indoor air pollution and psychosocial factor measurements were taken in the 2nd trimester of pregnancy. Circulating inflammatory markers (IL-1ß, Il-6, and TNF-α) were measured in serum in the infants at 6 weeks postnatal. Linear regression models were used to investigate associations between individual exposures and inflammatory markers. To investigate joint effects of environmental and psychosocial factors, Self-Organizing Maps (SOM) were used to create exposure profile clusters. These clusters were added to linear regression models to investigate the associations between exposure profiles and inflammatory markers. All models were adjusted for maternal age, maternal HIV status, and ancestry to control for confounding. Most indoor air pollutants were positively associated with inflammatory markers, particularly benzene and TNF-α in single pollutant models. No consistent patterns were found for psychosocial factors in single-exposure linear regression models. In joint effects analyses, the SOM profile with high indoor air pollution, low SES, and high maternal depressive symptoms were associated with higher inflammation. Indoor air pollutants were consistently associated with increased inflammation in both individual and joint effects models, particularly in combination with low SES and maternal depressive symptoms. The trend for individual psychosocial factors was not as clear, with mainly null associations. As we have observed pro- and anti-inflammatory effects, future research should investigate joint effects of these exposures on inflammation and their health effects.

Prevalence of university non-continuation and mental health conditions, and effect of mental health conditions on non-continuation: a systematic review and meta-analysis.

BACKGROUND: University non-continuation, also termed as university dropout in literature, is a concern for institutions. Elevated stress levels, mental distress, and psychiatric issues affect academic performance and thus may contribute to non-continuation. There is a lack of systematic reviews exploring the link between mental health and university non-continuation. AIM: This systematic review aims to bridge this gap, by investigating the prevalence of non-continuation and mental health conditions among university students, and the impact of mental health on university non-continuation. METHODS: Following PRISMA guidelines this review synthesized data from 67 studies, utilising both narrative synthesis and meta-analytic techniques. RESULTS: The results revealed that the included studies reported a range of university non-continuation rates (5.9% to 43.6%) with a pooled prevalence of 17.9%, 95% CI [14.2%, 22.3%]. The prevalence of mental health concerns among students varied widely (2.2% to 83.6%), with a pooled prevalence of 26.3%, 95% CI [16.0%, 40.0%]. Depression, OR = 1.143 (95% CI [1.086, 1.203] p<.001), stress, OR = 1.413 (95% CI [1.106, 1.805], p=.006), and other mental health conditions, OR = 1.266 (95% CI [1.133, 1.414], p<.001), were associated with higher non-continuation. CONCLUSION: Some mental health conditions elevate non-continuation risks, and addressing mental health may enhance student retention in higher education.