Genetics of environmental sensitivity to psychiatric and neurodevelopmental phenotypes: evidence from GWAS of monozygotic twins.

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.

The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

BACKGROUND: The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. METHODS: A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400µ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. RESULTS: 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417µ and 430µ in the No-VMIA and VMIA groups respectively) and improved to approximately 300µ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108µ and 79µ, p= 0.04). There was a mean of 7 injections after 12 months. CONCLUSION: Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

School-Based Screening and Brief Intervention for Adolescent Substance Use With Telehealth-Delivered Case Consultation and Education.

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is a public health framework for addressing adolescent substance use. Implementation of SBIRT in schools carries the potential to improve substance use treatment access and service acceptance for students, but faces barriers related to knowledge deficits, low comfort, and lack of training in screening and brief interventions among school-based mental health (SBMH) providers. This report describes the development and acceptability evaluation of a school-based SBIRT program designed to overcome common implementation barriers of SBIRT related to provider confidence, knowledge, and training deficits by supplementing the traditional model with telehealth-delivered addiction consultation and education (ACE). METHODS: Program components include core SBIRT trainings, telehealth-delivered ACE sessions, and outreach support for SBMH providers. Each ACE session included a didactic expert presentation on a clinical topic and a provider-presented patient case with discussion. Sessions were delivered using a Project ECHO-based hub-and-spoke format with monthly 1-hour virtual meetings. Interviews and surveys with SBMH providers on substance use screening and intervention practices and perceived barriers were used to inform program design choices and tailor the curriculum. Acceptability data were collected at 9 months. RESULTS: SBMH provider participants reported increased confidence, knowledge, and evidence-based screening and early intervention practices, and high acceptability, satisfaction, and benefit from the program. Ongoing barriers to referral to treatment were reported. CONCLUSION: This pilot study suggests that supplementing traditional SBIRT with telehealth-delivered ACE sessions can address common implementation barriers and serve as a scalable model to improve SBIRT adoption in schools.

Responding to the Youth Fentanyl Crisis: Practical Guidance for Child Psychiatrists.

Deaths due to unintentional opioid overdose among youth living in the United States have risen at an extraordinary rate over the past 4 years.1 After remaining stable over the preceding decade, the rate of drug overdose deaths increased more than 2.3-fold from 2019 to 2021 to a record high of 5.49 deaths per 100,000 youth.1 This rise in fatal overdoses is largely due to increased prevalence of illicitly manufactured fentanyl in the drug supply. In 2021, fentanyl was identified in 77.1% of overdose deaths among US adolescents, a 23.5-fold increase from 2010, compared to 13.3% for benzodiazepines, 5.8% for prescription opioids, and 2.3% for heroin.1 Compared to other phases of the opioid crisis, fentanyl-related overdoses are characterized by extraordinarily broad geographic and sociodemographic reach.

Systematic Review and Meta-Analysis: Medical and Recreational Cannabis Legalization and Cannabis Use Among Youth in the United States.

OBJECTIVE: Dramatic changes in state-level cannabis laws (CL) over the past 25 years have shifted societal beliefs throughout the United States, with unknown implications for youth. In the present study, we conducted an updated systematic review and meta-analysis examining estimated effects of medical cannabis legalization (MCL) and recreational cannabis legalization (RCL) on past-month cannabis use among US youth. METHOD: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, followed by a subsequent meta-analysis investigating the associations between state-level cannabis laws (ie, MCL vs non-MCL, and RCL vs non-RCL) and past-month cannabis use prevalence among US adolescents and young adults. Supplemental analyses examined age-group effects and design-related factors. RESULTS: Our search identified 4,604 citations, 34 and 30 of which were included in qualitative and quantitative analyses, respectively. Meta-analysis of MCL studies identified no significant association between MCL and change in past-month youth cannabis use (odds ratio [OR] = 0.981, 95% CI = 0.960, 1.003). Meta-analysis of RCL studies showed significantly increased odds of past-month cannabis use (OR = 1.134, 95% CI = 1.116-1.153). Meta-analysis of more recent studies, however, showed a significantly increased odds of past-month cannabis use among both adolescents and young adults (OR = 1.089, 95% CI = 1.015,1.169, and OR = 1.221, 95% CI = 1.188,1.255, respectively). CONCLUSION: Cannabis legalization has complex and heterogenous effects on youth use that may differ across law types. Our meta-analytic results showed modest positive effects of RCL on past-month cannabis use (more so in young adults than in adolescents) and minimal effects of MCL on these outcomes in US youth. Given the shift toward recreational legalization, additional focus on RCL effects is warranted.

Temporal-to-Nasal Macular Ganglion Cell and Inner Plexiform Layer Ratios in a Large Adult Twin Cohort: Correlations With Age and Heritability.

Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Results: Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Conclusions: Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.

Evaluation of an emergency department opt-out provider-driven HIV and syphilis screening and linkage-to-care program.

OBJECTIVE: While the effectiveness of emergency departments (ED) in screening for HIV and syphilis is understood, less is known about dual screening programs. We aim to evaluate the impact of an opt-out provider-initiated HIV and syphilis program on screening, diagnosis, and linkage to care outcomes. METHODS: We performed a retrospective review of patients screened pre (2014-2017) and post (2017-2021) program implementation. Primary outcomes include HIV and syphilis screening, incidence of positive tests, and proportion of patients linked to care. Secondary outcomes included pre-exposure prophylaxis (PrEP) referral and successful linkage rates for HIV-negative syphilis-positive patients. RESULTS: Pre-implementation, 882 HIV tests were performed, of which 22 (2.49%) were new cases and 18 (81.82%) were linked to care; 754 syphilis tests were performed, of which 33 (4.38%) were active infections and 30 (90.91%) were treated. No eligible patients received PrEP referral. Post-implementation, 12,999 HIV tests were performed, of which 73 (0.56%) were new cases and 55 (75.34%) were linked to care; 10,885 syphilis tests were performed, of which 216 (1.98%) were active infections and 188 (87.04%) were treated. 25 (9.09%) eligible patients were referred for PrEP, and four (16.0%) attended their appointment. CONCLUSIONS: Post-implementation, there was a 1373.81% and 1343.63% increase in screening, and a 231.82% and 554.55% increase in positive cases of HIV and syphilis, respectively. Dual screening programs can be successfully implemented within the existing ED framework to increase screening and early detection for HIV and syphilis.

Association Between Marijuana Laws and Suicide Among 12- to 25-Year-Olds in the United States From 2000 to 2019.

OBJECTIVE: Cannabis use is associated with suicide-related outcomes in both adolescents and adults, and may be increasing amid shifting cannabis policies. However, little is known about the impact of medical marijuana legalization (MML) and recreational marijuana legalization (RML) policies on youth suicide. Using 20 years of national data, we examined associations between MML, RML, and suicide-related mortality among US individuals aged 12 to 25 years, and assessed whether they varied based on age and sex. METHOD: Suicide deaths (N = 113,512) from the 2000-2019 National Vital Statistics System Multiple Cause of Death files for age groups 12 to 13, 14 to 16, 17 to 19, 20 to 22, and 23 to 25 years were examined in relation to time-varying cannabis law status using a staggered adoption difference-in-difference (DiD) approach with a negative binomial regression to determine associations between MML, RML, and suicide rates, controlling for individual- and state-level covariates and accounting for the varying effective dates of MML and RML by state. RESULTS: The overall unadjusted annual suicide rate was 10.93/100,000, varying from 9.76 (states without marijuana laws (ML)) to 12.78 (MML states) to 16.68 (RML states). In multivariable analysis, both MML (incidence rate ratio [IRR] = 1.10, 95% CI: 1.05-1.15) and RML (IRR = 1.16, 95% CI: 1.06-1.27) were associated with higher suicide rates among female youth compared to those in states without ML. Youth aged 14 to 16 years had higher rates of suicide in states with RML compared to states with MML (IRR = 1.14, 95% CI: 1.00-1.30) and states without ML (IRR = 1.09, 95% CI: 1.00-1.20). Findings were consistent across sensitivity analyses. CONCLUSION: MML and RML were associated with increased suicide-related mortality in female youth and 14- to- 16-year-old individuals of both sexes. Mechanisms through which cannabis policies are related to increased youth suicide warrant further study and should inform legislative reform.

Low concentration atropine and myopia: a narrative review of the evidence for United Kingdom based practitioners.

The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and myopic maculopathy which are associated with increased axial length. Pharmacological control of myopia progression with atropine has been investigated since the 19th century and the benefits of slowing myopia progression are considered against the side-effects of near blur and photophobia. More recently, randomised trials have focused on determining the optimum concentration of atropine leading to low-concentration atropine being used to manage myopia progression by practitioners across the world. Currently, in the United Kingdom, there is no licensed pharmacological intervention for myopia management. The aim of this review is to interpret the available data to inform clinical practice. We conducted a narrative review of the literature and identified peer-reviewed randomised controlled trials using the search terms 'myopia' and 'atropine', limited to the English language. We identified two key studies, which were the Atropine in the Treatment Of Myopia (ATOM) and Low-concentration Atropine for Myopia Progression (LAMP). Further studies were identified using the above search terms and the references from the identified literature. Atropine 0.01% has a modest effect on controlling axial length progression. Atropine 0.05% appears to be superior to atropine 0.01% in managing myopia progression. There is a dose-dependent rebound effect when treatment is stopped. Atropine is a well-tolerated, safe, and effective intervention. Treatment would be needed for several years and into adolescence, until axial length progression is stable.

Cone-driven strong flash electroretinograms in healthy adults: Prevalence of negative waveforms.

PURPOSE: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is selectively lost, a negative waveform might represent the response of the dark-adapted cone system. To investigate the dark-adapted cone-driven waveform in healthy individuals, we delivered flashes on a dim blue background, designed to saturate the rods, but minimally adapt the cones. METHODS: ERGs were recorded, using conductive fibre electrodes, in adults from the TwinsUK cohort. Responses to 13 cd m-2 s white xenon flashes (similar to the standard DA 10 flash), delivered on a blue background, were analysed. Photopic and scotopic strengths of the background were 1.3 and 30 cd m-2, respectively; through a dilated pupil, this is expected to largely saturate the rods, but adapt the cones much less than the standard ISCEV background. RESULTS: Mean (SD) participant age was 62.5 (11.3) years (93% female). ERGs from 203 right and 204 left eyes were included, with mean (SD) b/a ratios of 1.22 (0.28) and 1.18 (0.28), respectively (medians, 1.19 and 1.17). Proportions with negative waveforms were 23 and 26%, respectively. Right and left eye b/a ratios were strongly correlated (correlation coefficient 0.74, p < 0.0001). We found no significant correlation of b/a ratio with age. CONCLUSIONS: Over 20% of eyes showed b/a ratios less than 1, consistent with the notion that dark-adapted cone-driven responses to standard bright flashes can have negative waveforms. The majority had ratios greater than 1. Thus, whilst selective loss of rod function can yield a negative waveform (with reduced a-wave) in some, our findings also suggest that loss of rod function can occur without necessarily yielding a negative ERG. One potential limitation is possible mild cone system adaptation by the background.

Patterns of Polysubstance Use in Young Black and Latinx Sexual Minority Men and Transgender Women and Its Association with Sexual Partnership Factors: The PUSH Study.

Background: Adult studies have demonstrated that polysubstance use increases HIV acquisition risk through increased sexual behaviors, however, few studies have examined polysubstance in young Black and Latinx sexual minority men (SMM) and transgender women (TW). Methods: We used cross-sectional data from 466 young Black and Latinx SMM and TW living in four high HIV-burden US cities enrolled in the PUSH Study, a status-neutral randomized control trial to increase HIV prevention and treatment adherence. We examined data for patterns of polysubstance use comparing age differences of use and explored associations between substance use and sexual partnership factors - inconsistent condom use, pressure to have condomless anal sex, and older partner, using bivariate and multivariate analyses. Results: Most participants described prior substance use with alcohol and cannabis being most common (76% each) and 23% described other illicit drug use, including stimulants, cocaine, hallucinogens, sedatives, opioids, and inhalants. Polysubstance use was common with nearly half (47%) of participants reporting alcohol and cannabis use, 20% reporting alcohol, cannabis, and one other illicit drug use, and 19% reporting alcohol or cannabis use plus one other illicit drug use. Polysubstance use was associated with greater adjusted odds of pressure to have condomless anal sex, older partner (>5 years older), and inconsistent condom use. Conclusions: Associations of polysubstance use with sexual practices and sexual partnerships that are known predictors of HIV acquisition or transmission among Black and Latinx SMM and TW underscore the need for combination interventions that include substance use treatment alongside antiretroviral-based and partner-based HIV prevention and treatment interventions.Trial Registration: ClinicalTrials.gov Identifier: NCT03194477.

A Christian Faith-Based Facebook Intervention for Smoking Cessation in Rural Communities (FAITH-CORE): Protocol for a Community Participatory Development Study.

BACKGROUND: Tobacco smoking remains the leading cause of preventable morbidity and mortality in the United States, with significant rural-urban disparities. Adults who live in rural areas of the United States have among the highest tobacco smoking rates in the nation and experience a higher prevalence of smoking-related deaths and deaths due to chronic diseases for which smoking is a causal risk factor. Barriers to accessing tobacco use cessation treatments are a major contributing factor to these disparities. Adults living in rural areas experience difficulty accessing tobacco cessation services due to geographical challenges, lack of insurance coverage, and lack of health care providers who treat tobacco use disorders. The use of digital technology could be a practical answer to these barriers. OBJECTIVE: This report describes a protocol for a study whose main objectives are to develop and beta test an innovative intervention that uses a private, moderated Facebook group platform to deliver peer support and faith-based cessation messaging to enhance the reach and uptake of existing evidence-based smoking cessation treatment (EBCT) resources (eg, state quitline coaching programs) for rural adults who smoke. METHODS: We will use the Integrated Theory of Health Behavior Change, surface or deep structure frameworks to guide intervention development, and the community-based participatory research (CBPR) approach to identify and engage with community stakeholders. The initial content library of moderator postings (videos and text or image postings) will be developed using existing EBCT material from the Centers for Disease Control and Prevention Tips from Former Smokers Campaign. The content library will feature topics related to quitting smoking, such as coping with cravings and withdrawal and using EBCTs with faith-based message integration (eg, Bible quotes). A community advisory board and a community engagement studio will provide feedback to refine the content library. We will also conduct a beta test of the intervention with 15 rural adults who smoke to assess the recruitment feasibility and preliminary intervention uptake such as engagement, ease of use, usefulness, and satisfaction to further refine the intervention based on participant feedback. RESULTS: The result of this study will create an intervention prototype that will be used for a future randomized controlled trial. CONCLUSIONS: Our CBPR project will create a prototype of a Facebook-delivered faith-based messaging and peer support intervention that may assist rural adults who smoke to use EBCT. This study is crucial in establishing a self-sufficient smoking cessation program for the rural community. The project is unique in using a moderated social media platform providing peer support and culturally relevant faith-based content to encourage adult people who smoke to seek treatment and quit smoking. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52398.

Changes in Refractive Error During Young Adulthood: The Effects of Longitudinal Screen Time, Ocular Sun Exposure, and Genetic Predisposition.

Purpose: Changes in refractive error during young adulthood is common yet risk factors at this age are largely unexplored. This study explored risk factors for these changes, including gene-environmental interactions. Methods: Spherical equivalent refraction (SER) and axial length (AL) for 624 community-based adults were measured at 20 (baseline) and 28 years old. Participants were genotyped and their polygenic scores (PGS) for refractive error calculated. Self-reported screen time (computer, television, and mobile devices) from 20 to 28 years old were collected prospectively and longitudinal trajectories were generated. Past sun exposure was quantified using conjunctival ultraviolet autofluorescence (CUVAF) area. Results: Median change in SER and AL were -0.023 diopters (D)/year (interquartile range [IQR] = -0.062 to -0.008) and +0.01 mm/year (IQR = 0.000 to 0.026), respectively. Sex, baseline myopia, parental myopia, screen time, CUVAF, and PGS were significantly associated with myopic shift. Collectively, these factors accounted for approximately 20% of the variance in refractive error change, with screen time, CUVAF, and PGS each explaining approximately 1% of the variance. Four trajectories for total screen time were found: "consistently low" (n = 148), "consistently high" (n = 250), "consistently very high" (n = 76), and "increasing" (n = 150). Myopic shift was faster in those with "consistently high" or "consistently very high" screen time compared to "consistently-low" (P ≤ 0.031). For each z-score increase in PGS, changes in SER and AL increased by -0.005 D/year and 0.002 mm/year (P ≤ 0.045). Of the three types of screen time, only computer time was associated with myopic shift (P ≤ 0.040). There was no two- or three-way interaction effect between PGS, CUVAF, or screen time (P ≥ 0.26). Conclusions: Higher total or computer screen time, less sun exposure, and genetic predisposition are each independently associated with greater myopic shifts during young adulthood. Given that these factors explained only a small amount of the variance, there are likely other factors driving refractive error change during young adulthood.

Greater adherence to a mediterranean diet is associated with lower C-reactive protein (CRP) levels, but not to lower odds of having dry eye disease.

PURPOSE: To investigate the hypothesis that a Mediterranean diet is associated with a lower risk of having dry eye disease (DED) in the general population. METHODS: DED was assessed using the Women's Health Study (WHS) dry eye questionnaire in 58,993 participants from the Dutch Lifelines Cohort with complete available dietary data (20-94 years, 60% female). Level of adherence to a traditional Mediterranean diet was assessed using the modified Mediterranean Diet Score (mMDS). High-sensitivity C-reactive Protein (hsCRP) was included as a marker of whole-body inflammation. Logistic regressions were used to examine the relationship between WHS-defined DED and mMDS, corrected for age, sex, BMI, education, income, and 48 potentially confounding comorbidities. The association between mMDS and hsCRP, and hsCRP and DED, was further explored in separate regressions. RESULTS: Of all participants, 9.1% had DED. In contrast to the hypothesis, higher mMDS levels were associated with greater odds of DED, corrected for demographics, smoking status, BMI, and comorbidities (OR 1.034, 95%CI: 1.015 to 1.055, P = 0.001). Moreover, there was a highly significant relationship between increasing mMDS and lower circulating hsCRP levels; however, there was no significant relationship between hsCRP and DED. CONCLUSIONS: Stronger adherence to a Mediterranean diet does not appear to be associated with lower odds of having DED in the general population. Furthermore, there was no association between hsCRP and DED in this study. However, the previously described link between a Mediterranean diet and lower hsCRP was confirmed in this large population-based study.

Brain Functional Connectome Defines a Transdiagnostic Dimension Shared by Cognitive Function and Psychopathology in Preadolescents.

BACKGROUND: Cognitive function and general psychopathology are two important classes of human behavior dimensions that are individually related to mental disorders across diagnostic categories. However, whether these two transdiagnostic dimensions are linked to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear. METHODS: The current study is a longitudinal investigation with 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study at ages 9 to 10 years at the onset of the study. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multidomain behavioral assessments including cognitive functions and psychopathological measures. For the latent resting-state functional connectivity factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using 2-year follow-up data, and its genetic association was evaluated using twin data from the same cohort. RESULTS: A latent functional connectome pattern was identified that showed a strong and generalizable association with the multidomain behavioral assessments (5-fold cross-validation: ρ = 0.68-0.73 for the training set [n = 5096]; ρ = 0.56-0.58 for the test set [n = 1476]). This functional connectome pattern was highly heritable (h2 = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with the cumulative number of psychiatric disorders assessed concurrently and at 2 years post-magnetic resonance imaging scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period. CONCLUSIONS: These findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in the development of psychiatric disorders during early adolescence.

The radiology quality assurance process in the Yorkshire Lung Screening Trial, and findings from the baseline round of low dose CT screening for lung cancer.

OBJECTIVE: As lung cancer screening is rolled-out, there is a need to develop an effective quality assurance (QA) framework around radiology reporting to ensure optimal implementation. Here, we report a structured QA process for low-dose CT (LDCT) scans performed in the Yorkshire Lung Screening Trial. METHODS: Negative LDCT scans were single read after using computer-aided detection software. The radiology QA process included reviewing 5% of negative scans selected at random, and all cases with a subsequent diagnosis of extrapulmonary cancer or interval lung cancer not detected on the baseline scan. Radiologists were not informed of the reason for review and original radiology reports were scored as either "satisfactory", "satisfactory with learning points", or "unsatisfactory". RESULTS: From 6650 participants undergoing LDCT screening, 208 negative scans were reviewed alongside 11 cases with subsequent extrapulmonary cancer and 10 cases with interval lung cancer. Overall, only three reports were ultimately judged "unsatisfactory", 1% of randomly selected negative scans (n = 2/208) and one interval lung cancer scan (n = 1/10). Four out of a total of five cases judged "satisfactory with learning points" were related to oesophageal abnormalities where the participant was subsequently diagnosed with oesophageal cancer. CONCLUSION: The described process attempts to minimise bias in retrospective review of screening scans, and may represent a framework for future QA of national screening programmes. ADVANCES IN KNOWLEDGE: This study describes a structured QA process for a lung cancer screening programme, involving blinded second-read of LDCT screening scans to ensure fair, constructive audit of clinical performance.

Cannabis Use Associations with Adverse Psychosocial Functioning among North American College Students.

Introduction: Adolescent-onset cannabis use (CU) (before age 18) is associated with multiple adverse psychosocial outcomes, but rates of CU peak between the ages of 18 and 22, coinciding with college matriculation. Whether CU among college-enrolled young adults is associated with similar psychosocial outcomes is poorly understood. In the present study, we examined relationships between CU and multiple psychosocial outcomes in North American college students. Methods: Data for this report come from N = 40,250 North American college students ages 18-to-25 years (mean age = 20.7 years, 69% female, 66% Caucasian) who participated in the Healthy Minds Study (HMS) 2016-17. HMS is a web-based annual survey querying multiple mental health, substance use, and psychosocial variables in representative student populations from 53 universities across North America. Student respondents were stratified in two groups based upon their self-report of past 30-day CU and compared on psychosocial variables. Results: Approximately 20% (n = 8,327) of student respondents reported past 30-day CU. After adjusting for socio-demographics, knowledge of campus services, and use of other drugs, the odds of depression (aOR = 1.3), suicidal thoughts and behaviors (aORs ∼1.4-1.7), anxiety (aOR = 1.2), eating disorders (aOR = 1.2), and violence victimization (aOR = 1.4) were all higher for CU students. Additionally, CU students had higher rates of other drug use and lower rates of perceived supportive relationships. Conclusion: Our results indicated that CU is common among North American college students and associated with adverse psychosocial consequences across multiple domains. Based upon these findings, colleges should consider expanding educational, prevention, and early-intervention programs for students who use cannabis.

Psilocybin history, action and reaction: A narrative clinical review.

Hallucinogenic mushrooms have been used in religious and cultural ceremonies for centuries. Of late, psilocybin, the psychoactive compound in hallucinogenic mushrooms, has received increased public interest as a novel drug for treating mood and substance use disorders (SUDs). In addition, in recent years, some states in the United States have legalized psilocybin for medical and recreational use. Given this, clinicians need to understand the potential benefits and risks related to using psilocybin for therapeutic purposes so that they can accurately advise patients. This expert narrative review summarizes the scientific basis and clinical evidence on the safety and efficacy of psilocybin-assisted therapy for treating psychiatric disorders and SUDs. The results of this review are structured as a more extensive discussion about psilocybin's history, putative mechanisms of action, and recent legislative changes to its legal status. There is modest evidence of psilocybin-assisted therapy for treating depression and anxiety disorders. In addition, early data suggest that psilocybin-assisted therapy may effectively reduce harmful drinking in patients with alcohol use disorders. The evidence further suggests psilocybin, when administered under supervision (psilocybin-assisted therapy), the side effects experienced are mild and transient. The occurrence of severe adverse events following psilocybin administration is uncommon. Still, a recent clinical trial found that individuals in the psilocybin arm had increased suicidal ideations and non-suicidal self-injurious behaviors. Given this, further investigation into the safety and efficacy of psilocybin-assisted therapy is warranted to determine which patient subgroups are most likely to benefit and which are most likely to experience adverse outcomes related to its use.

The Role of Mitophagy in Glaucomatous Neurodegeneration.

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.