Association between cannabis potency and mental health in adolescence.

INTRODUCTION: In legal and illegal markets, high-potency cannabis (>10 % delta-9-tetrahydrocannabinol (THC)) is increasingly available. In adult samples higher-potency cannabis has been associated with mental health disorder but no studies have considered associations in adolescence. METHODS: A population-wide study compared no, low and high potency cannabis using adolescents (aged 13-14 years) self-reported symptoms of probable depression, anxiety, and auditory hallucinations. RESULTS: Of the 6672 participants, high-potency cannabis was used by 2.6 % (n=171) and low-potency by 0.6 % (n=38). After adjustment for sociodemographic factors, tobacco and alcohol use, in comparison to participants who had never used cannabis, people who had used high-potency but not low-potency cannabis were more likely to report symptoms of depression (odds ratio 1.59 [95 % confidence interval 1.06, 2.39), anxiety (OR 1.45, 95 % CI 0.96, 2.20), and auditory hallucinations (OR 1.56, 95 % CI 0.98, 2.47). CONCLUSIONS: High-potency cannabis use is associated with an increased risk of probable mental health disorders. Services and programming to minimise drug harms may need to be adapted to pay more attention to cannabis potency.

Polygenic risk of social isolation behavior and its influence on psychopathology and personality.

Social isolation has been linked to a range of psychiatric issues, but the behavioral component that drives it is not well understood. Here, a genome-wide associations study (GWAS) was carried out to identify genetic variants that contribute specifically to social isolation behavior (SIB) in up to 449,609 participants from the UK Biobank. 17 loci were identified at genome-wide significance, contributing to a 4% SNP-based heritability estimate. Using the SIB GWAS, polygenic risk scores (PRS) were derived in ALSPAC, an independent, developmental cohort, and used to test for association with self-reported friendship scores, comprising items related to friendship quality and quantity, at age 12 and 18 to determine whether genetic predisposition manifests during childhood development. At age 18, friendship scores were associated with the SIB PRS, demonstrating that the genetic factors can predict related social traits in late adolescence. Linkage disequilibrium (LD) score correlation using the SIB GWAS demonstrated genetic correlations with autism spectrum disorder (ASD), schizophrenia, major depressive disorder (MDD), educational attainment, extraversion, and loneliness. However, no evidence of causality was found using a conservative Mendelian randomization approach between SIB and any of the traits in either direction. Genomic Structural Equation Modeling (SEM) revealed a common factor contributing to SIB, neuroticism, loneliness, MDD, and ASD, weakly correlated with a second common factor that contributes to psychiatric and psychotic traits. Our results show that SIB contributes a small heritable component, which is associated genetically with other social traits such as friendship as well as psychiatric disorders.

Air and Noise Pollution Exposure in Early Life and Mental Health From Adolescence to Young Adulthood.

Importance: Growing evidence associates air pollution exposure with various psychiatric disorders. However, the importance of early-life (eg, prenatal) air pollution exposure to mental health during youth is poorly understood, and few longitudinal studies have investigated the association of noise pollution with youth mental health. Objectives: To examine the longitudinal associations of air and noise pollution exposure in pregnancy, childhood, and adolescence with psychotic experiences, depression, and anxiety in youths from ages 13 to 24 years. Design, Setting, and Participants: This cohort study used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort founded in 1991 through 1993 in Southwest England, United Kingdom. The cohort includes over 14 000 infants with due dates between April 1, 1991, and December 31, 1992, who were subsequently followed up into adulthood. Data were analyzed October 29, 2021, to March 11, 2024. Exposures: A novel linkage (completed in 2020) was performed to link high-resolution (100 m2) estimates of nitrogen dioxide (NO2), fine particulate matter under 2.5 µm (PM2.5), and noise pollution to home addresses from pregnancy to 12 years of age. Main outcomes and measures: Psychotic experiences, depression, and anxiety were measured at ages 13, 18, and 24 years. Logistic regression models controlled for key individual-, family-, and area-level confounders. Results: This cohort study included 9065 participants who had any mental health data, of whom (with sample size varying by parameter) 51.4% (4657 of 9051) were female, 19.5% (1544 of 7910) reported psychotic experiences, 11.4% (947 of 8344) reported depression, and 9.7% (811 of 8398) reported anxiety. Mean (SD) age at follow-up was 24.5 (0.8) years. After covariate adjustment, IQR increases (0.72 µg/m3) in PM2.5 levels during pregnancy (adjusted odds ratio [AOR], 1.11 [95% CI, 1.04-1.19]; P = .002) and during childhood (AOR, 1.09 [95% CI, 1.00-1.10]; P = .04) were associated with elevated odds for psychotic experiences. Pregnancy PM2.5 exposure was also associated with depression (AOR, 1.10 [95% CI, 1.02-1.18]; P = .01). Higher noise pollution exposure in childhood (AOR, 1.19 [95% CI, 1.03-1.38]; P = .02) and adolescence (AOR, 1.22 [95% CI, 1.02-1.45]; P = .03) was associated with elevated odds for anxiety. Conclusions and Relevance: In this longitudinal cohort study, early-life air and noise pollution exposure were prospectively associated with 3 common mental health problems from adolescence to young adulthood. There was a degree of specificity in terms of pollutant-timing-outcome associations. Interventions to reduce air and noise pollution exposure (eg, clean air zones) could potentially improve population mental health. Replication using quasi-experimental designs is now needed to shed further light on the underlying causes of these associations.

Incident psychotic experiences following self-reported use of high-potency cannabis: Results from a longitudinal cohort study.

BACKGROUND AND AIMS: High-potency cannabis has been associated with increased risk of psychosis, but a lack of prospective data hinders understanding of causality in this relationship. This study aimed to combine prospective report of cannabis use with retrospective report of potency to infer the potency of cannabis used in adolescence and explore whether use of cannabis, and the use of high-potency cannabis, in adolescence is associated with incident psychotic experiences. DESIGN: Population-based birth cohort study. SETTING: United Kingdom. PARTICIPANTS: n = 5570 participants who reported on any cannabis use (yes/no) age 16 and 18 years, and n = 1560 participants from this group who also retrospectively reported on cannabis potency. MEASUREMENTS: In questionnaires at ages 16 and 18, individuals self-reported lifetime cannabis use, and at age 24, participants reported the type of cannabis they most commonly used in the whole time since first using cannabis. Psychotic experiences were assessed at age 24 years using the semi-structured Psychosis-Like Symptom Interview, with incident defined as new-onset occurring between ages 19 and 24 years. FINDINGS: Use of high-potency cannabis at age 16 or 18 was associated with twice the likelihood of experiencing incident psychotic experiences from age 19-24 (Odds Ratio 2.15, 95% Confidence Intervals 1.13-4.06). There was less evidence for an effect of any cannabis use on incident psychotic experiences (Odds Ratio 1.45, 95% Confidence Intervals 0.94-2.12). CONCLUSIONS: Use of high-potency cannabis appears to be associated with increased likelihood of psychotic experiences.

Association of early-life exposure to air and noise pollution with youth mental health: findings from the ALSPAC cohort.

BACKGROUND: Increasing evidence suggests that air pollution exposure contributes to the development of mental health problems, including psychosis and depression. However, little is known about the importance of early-life exposure, nor the potential role of noise pollution, a correlate of air pollution. We examined the association of exposure to air and noise pollution from pregnancy to age 12 years with three mental health problems assessed at ages 12, 18, and 24 years. METHODS: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), which tracks the development of about 14 000 babies who had expected delivery dates between April 1, 1991, and Dec 31, 1992, in Avon, UK. This was linked with novel data on nitrogen dioxide, PM2·5, and noise pollution in pregnancy, childhood (ages 1-9 years), and adolescence (ages 10-12 years). Psychotic experiences, depression, and anxiety were measured at ages 12, 18, and 24 years. Logistic regression models were controlled for individual-level, family-level, and area-level confounders, and e-values were calculated to estimate residual confounding. FINDINGS: Participants exposed to higher PM2.5, particularly during pregnancy, had greater odds for psychotic experiences (adjusted odds ratio 1·17 [95% CI 1·05-1·30]) and depression (1·11 [1·01-1·22]). There was little evidence associating nitrogen dioxide or noise pollution with psychotic experiences or depression. Conversely, higher nitrogen dioxide (but not PM2·5) exposure in pregnancy (1·16 [1·01-1·33]), and higher noise pollution in childhood (1·20 [1·06-1·37]) and adolescence (1·17 [1·02-1·35]), were associated with greater odds for anxiety. INTERPRETATION: Our study builds on evidence linking air pollution to psychosis and depression and provides rare longitudinal evidence linking noise pollution to anxiety. Our findings indicate that air pollution exposure earlier in development (eg, during pregnancy) might be particularly important, and suggest a degree of specificity in terms of pollutant-outcome associations. If causal, our findings suggest that interventions to reduce air pollution would improve global mental health. FUNDING: Wellcome Trust, UK Medical Research Council-Wellcome, and University of Bristol.

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators.

BACKGROUND AND HYPOTHESIS: Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood. STUDY DESIGN: We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula. STUDY RESULTS: In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results. CONCLUSIONS: Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences.

Assessing the association between global structural brain age and polygenic risk for schizophrenia in early adulthood: A recall-by-genotype study.

Neuroimaging studies consistently show advanced brain age in schizophrenia, suggesting that brain structure is often 'older' than expected at a given chronological age. Whether advanced brain age is linked to genetic liability for schizophrenia remains unclear. In this pre-registered secondary data analysis, we utilised a recall-by-genotype approach applied to a population-based subsample from the Avon Longitudinal Study of Parents and Children to assess brain age differences between young adults aged 21-24 years with relatively high (n = 96) and low (n = 93) polygenic risk for schizophrenia (SCZ-PRS). A global index of brain age (or brain-predicted age) was estimated using a publicly available machine learning model previously trained on a combination of region-wise gray-matter measures, including cortical thickness, surface area and subcortical volumes derived from T1-weighted magnetic resonance imaging (MRI) scans. We found no difference in mean brain-PAD (the difference between brain-predicted age and chronological age) between the high- and low-SCZ-PRS groups, controlling for the effects of sex and age at time of scanning (b = -.21; 95% CI -2.00, 1.58; p = .82; Cohen's d = -.034; partial R2 = .00029). These findings do not support an association between SCZ-PRS and brain-PAD based on global age-related structural brain patterns, suggesting that brain age may not be a vulnerability marker of common genetic risk for SCZ. Future studies with larger samples and multimodal brain age measures could further investigate global or localised effects of SCZ-PRS.

The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences.

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders.

Functional Outcomes Among Young People With Trajectories of Persistent Childhood Psychopathology.

Importance: Understanding which children in the general population are at greatest risk of poor functional outcomes could improve early screening and intervention strategies. Objective: To investigate the odds of poor outcomes in emerging adulthood (ages 17 to 20 years) for children with different mental health trajectories at ages 9 to 13 years. Design, Setting, and Participants: Growing Up in Ireland is a longitudinal, nationally representative population-based cohort study. Data collection began in August 2007 and was repeated most recently in September 2018. All results were weighted to account for sampling bias and attrition and were adjusted for socioeconomic factors. Data analysis took place from October 2022 to April 2023. Exposure: Four latent classes captured variation in mental health in children aged 9 and 13 years, based on the parent-completed Strengths and Difficulties Questionnaire. Classes included no psychopathology, internalizing, externalizing, and high (comorbid) psychopathology. Those who remained in the same class from ages 9 to 13 years were included. Main Outcomes and Measures: Poor functional outcomes in emerging adulthood were measured at approximate ages 17 years (range, 16 to 18 years) and 20 years (range, 19 to 21 years). Outcomes included poor mental health, poor physical health, social isolation, heavy substance use, frequent health service use, poor subjective well-being, and adverse educational/economic outcomes. Results: Of 5141 included participants, 2618 (50.9%) were male. A total of 3726 (72.5%) were classed as having no childhood psychopathology, 1025 (19.9%) as having persistent externalizing psychopathology, 243 (4.7%) as having persistent internalizing psychopathology, and 147 (2.9%) as having persistent high psychopathology. Having any childhood psychopathology was associated with poorer functional outcomes in emerging adulthood. The internalizing group had elevated odds of most outcomes except for heavy substance use (range of odds ratios [ORs]: 1.38 [95% CI, 1.05-1.81] for frequent health service use to 3.08 [95% CI, 2.33-4.08] for poor mental health). The externalizing group had significantly elevated odds of all outcomes, albeit with relatively small effect sizes (range of ORs: 1.38 [95% CI, 1.19-1.60] for frequent health service use to 1.98 [95% CI, 1.67-2.35] for adverse educational/economic outcomes). The high psychopathology group had elevated odds of all outcomes (nonsignificantly for frequent health service use), though with wide confidence intervals (range of ORs: 1.53 [95% CI, 1.06-2.21] for poor physical health to 2.91 [95% CI, 2.05-4.12] for poor mental health). Female participants with any psychopathology had significantly higher odds of poor physical health and frequent health service use compared with male participants with any psychopathology. Conclusions and Relevance: In this longitudinal cohort study, childhood psychopathology was associated with a widespread pattern of functional impairment in emerging adulthood. Findings point to the need for a wider range of preventive interventions in child and adolescent mental health services.

Association of cannabis, cannabidiol and synthetic cannabinoid use with mental health in UK adolescents.

BACKGROUND: Cannabis has been associated with poorer mental health, but little is known of the effect of synthetic cannabinoids or cannabidiol (often referred to as CBD). AIMS: To investigate associations of cannabis, synthetic cannabinoids and cannabidiol with mental health in adolescence. METHOD: We conducted a cross-sectional analysis with 13- to 14-year-old adolescents across England and Wales in 2019-2020. Multilevel logistic regression was used to examine the association of lifetime use of cannabis, synthetic cannabinoids and cannabidiol with self-reported symptoms of probable depression, anxiety, conduct disorder and auditory hallucinations. RESULTS: Of the 6672 adolescents who participated, 5.2% reported using of cannabis, 1.9% reported using cannabidiol and 0.6% reported using synthetic cannabinoids. After correction for multiple testing, adolescents who had used these substances were significantly more likely to report a probable depressive, anxiety or conduct disorder, as well as auditory hallucinations, than those who had not. Adjustment for socioeconomic disadvantage had little effect on associations, but weekly tobacco use resulted in marked attenuation of associations. The association of cannabis use with probable anxiety and depressive disorders was weaker in those who reported using cannabidiol than those who did not. There was little evidence of an interaction between synthetic cannabinoids and cannabidiol. CONCLUSIONS: To our knowledge, this study provides the first general population evidence that synthetic cannabinoids and cannabidiol are associated with probable mental health disorders in adolescence. These associations require replication, ideally with prospective cohorts and stronger study designs.

Does a history of cannabis use influence onset and course of schizophrenia?

INTRODUCTION: While evidence strongly supports a causal effect of cannabis on psychosis, it is less clear whether the symptom pattern, clinical course, and outcomes differ in cases of schizophrenia with and without a background of cannabis use. METHODS: Analysis of medical records from a longitudinal follow-up of Swedish conscripts with data on cannabis use in adolescence and subsequent incidence of schizophrenia. One hundred sixty patients with schizophrenia were assessed using the OPCRIT protocol. Cases were validated for diagnosis schizophrenia according to OPCRIT. RESULTS: Patients with a cannabis history (n = 32), compared to those without (n = 128), had an earlier age at onset, a higher number of hospital admissions and a higher total number of hospital days. There was no significant difference in type of onset and clinical symptom profiles between the groups. CONCLUSION: Our findings indicate that the disease burden of schizophrenia is greater in individuals who use cannabis during adolescence. Strengthening evidence on causality and teasing out long-term effects of pre-illness cannabis use from continued post-illness has clinical implications for improving schizophrenia outcomes.

Associations among psychosis, mood, anxiety, and posttraumatic stress symptoms: A network analysis.

The associations among psychotic experiences (i.e., hallucinations and delusions), trauma exposure, and posttraumatic stress symptoms are complex and multidirectional. Using network analysis to understand how psychotic experiences and symptoms of posttraumatic stress disorder (PTSD) relate to one another may identify new interventional targets to treat comorbidity and its underlying pathological processes. This study aimed to use network analysis to examine the associations among psychotic experiences; negative symptoms of psychosis; and symptoms of PTSD, anxiety, and depression. In this population-based cohort study, 4,472 participants (36.7% male) were assessed for psychotic experiences, negative symptoms of psychosis, PTSD, anxiety, and depression at age 23 (M = 23.86 years, SD = 0.520) or 24 years (M = 24.03, SD = 0.848). Associations among symptoms were assessed via network analysis. Exploratory graph analysis identified three clusters of densely connected symptoms within the overall network: psychotic experiences; PTSD symptoms; and depressive and anxiety symptoms and negative symptoms of psychosis. Psychotic experiences had the strongest associations with other symptoms in the network, and symptoms of anxiety played a key role in bridging psychotic experiences, symptoms of PTSD, and depressive symptoms. Consistent with the stress reactivity and affective models for psychotic experiences, the results suggest that symptoms of anxiety and emotional distress (e.g., hyperarousal, panic) may have a key role in the development and maintenance of psychotic experiences and symptoms of PTSD. Targeting these symptoms may ameliorate symptom burden transdiagnostically.

Empirically driven transdiagnostic stages in the development of mood, anxiety and psychotic symptoms in a cohort of youth followed from birth.

Staging models with transdiagnostic validity across mood, psychotic, and anxiety disorders could advance early intervention efforts as well as our understanding of the common underpinnings of such psychopathology. However, there are few well-supported operationalisations for such transdiagnostic models, particularly in community-based samples. We aimed to explore the inter-relationships among mood, psychotic, and anxiety symptom stages, and their common risk factors to develop data-informed transdiagnostic stages. We included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective ongoing birth cohort study. We developed operational thresholds for stages of depressive, hypomanic, anxiety, and psychotic symptoms based on the existing literature, refined further by expert consensus. We selected 1b level as the primary stage or outcome of interest. This represents moderate symptoms that are likely to be associated with the onset of the need for clinical mental health care. We used questionnaire and clinic data completed by young people ages 18 and 21 years. We used descriptive methods and network analyses to examine the overlap among Stage 1b psychopathology. We then examined the patterns of relationships between several risk factors and 1b stages using logistic regressions. Among 3269 young people with data available to determine all symptom stages, 64.3% were female and 96% Caucasian. Descriptive and network analyses indicated that 1b level depressive, anxiety, and psychotic symptom stages were inter-related while hypomania was not. Similarly, anxiety, depressive, and psychotic 1b stages were associated with the female sex, more emotional and behavioral difficulties in early adolescence, and life events in late adolescence. Hypomania was not related to any of these risk factors. Given their inter-relationships and similar risk factors, anxiety, psychotic and depressive, symptoms could be combined to form a transdiagnostic stage in this cohort. Such empirical transdiagnostic stages could help with prognostication and indicated prevention in youth mental health.

Association Between Gender Minority Status and Mental Health in High School Students.

PURPOSE: Adolescence is a phase when young people begin to explore their gender identity. Adolescents who identify as a gender minority are vulnerable to experiencing mental health problems due to stigmatization of their identity. METHODS: A population-wide study compared gender minority and cisgender students (aged 13-14 years) self-reported symptoms of probable depression, anxiety, and conduct disorder, and auditory hallucinations, including the distress and frequency of hallucinations. RESULTS: Gender minority students compared to cisgender students had four times the odds of reporting a probable depressive disorder, anxiety disorder, auditory hallucinations, but not conduct disorder. Of those who reported a hallucination, gender minority students were more likely to report hearing them daily but were no more likely to find them distressing. DISCUSSION: Gender minority students experience a disproportionate burden of mental health problems. Services and programming should be adapted to better support gender minority high-school students.

Stratification of adolescents across mental phenomena emphasizes the importance of transdiagnostic distress: a replication in two general population cohorts.

Characterizing patterns of mental phenomena in epidemiological studies of adolescents can provide insight into the latent organization of psychiatric disorders. This avoids the biases of chronicity and selection inherent in clinical samples, guides models of shared aetiology within psychiatric disorders and informs the development and implementation of interventions. We applied Gaussian mixture modelling to measures of mental phenomena from two general population cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 3018) and the Neuroscience in Psychiatry Network (NSPN, n = 2023). We defined classes according to their patterns of both positive (e.g. wellbeing and self-esteem) and negative (e.g. depression, anxiety, and psychotic experiences) phenomena. Subsequently, we characterized classes by considering the distribution of diagnoses and sex split across classes. Four well-separated classes were identified within each cohort. Classes primarily differed by overall severity of transdiagnostic distress rather than particular patterns of phenomena akin to diagnoses. Further, as overall severity of distress increased, so did within-class variability, the proportion of individuals with operational psychiatric diagnoses. These results suggest that classes of mental phenomena in the general population of adolescents may not be the same as those found in clinical samples. Classes differentiated only by overall severity support the existence of a general, transdiagnostic mental distress factor and have important implications for intervention.

Epidemiology of posttraumatic stress disorder: A prospective cohort study based on multiple nationwide Swedish registers of 4.6 million people.

BACKGROUND: Experiencing exceptionally threatening or horrifying traumas can lead to posttraumatic stress disorder (PTSD). Increasing political unrest/war/natural disasters worldwide could cause more traumatic events and change the population burden of PTSD. Most PTSD research is based on surveys, prone to selection/recall biases with inconsistent results. The aim was therefore, to use register-based data to identify the occurrence of PTSD and contributing factors in the Swedish general population. METHODS: This register-based cohort study used survival analysis. Individuals born between 1960-1995, aged ≥15 years, registered and living in Sweden, not emigrating, anytime between 1990-2015, not receiving specialized care for PTSD before 2006 were included (N = 4,673,764), and followed from their 15th/16th birth date until first PTSD diagnosis between 2006-2016 or study endpoint (31-December-2016). PTSD cases (ICD-10: F43.1) were identified from the national patient register. Mean follow-up time was 18.8 years. RESULTS: Between 2006-2016, the incidence of specialized healthcare utilization for PTSD nearly doubled, and 0.7% of the study population received such care. The highest risk was observed for refugees [aHR 8.18; 95% CI:7.85-8.51] and for those with depressive disorder [aHR 4.51; 95% CI:3.95-5.14]. Higher PTSD risk was associated with female sex, older age, low education, single parenthood, low household income, urbanicity, and being born to a foreign-born parent. CONCLUSIONS: PTSD is more common among refugee migrants, individuals with psychiatric disorders, and the socioeconomically disadvantaged. It is important that provision of services for PTSD are made available, particularly to these higher risk, and often hard-to-reach groups.

Person-Centered Trajectories of Psychopathology From Early Childhood to Late Adolescence.

Importance: The understanding of the development of psychopathology has been hampered by a reliance on cross-sectional data and symptom- or disorder-centered methods. Person-centered methods can accommodate both the problems of comorbidity and the movement between different psychopathological states at different phases of development. Objective: To examine the profiles and map the trajectories of psychopathology from early childhood to late adolescence. Design, Setting, and Participants: This cohort study used 2 longitudinal nationally representative community-based cohorts from the Growing Up in Ireland study covering developmental periods from early childhood to late adolescence. Data in this investigation came from children and their families who participated in all waves of cohorts recruited in 2008 (children ages 3, 5, and 9 years) and 1998 (adolescents ages 9, 13, and 17 or 18 years). Both samples were weighted to account for representation and attrition. Latent transition analyses were used to map the trajectories of psychopathology. Data were analyzed between October 2020 and September 2021. Main Outcomes and Measures: Psychopathology was measured using the Strengths and Difficulties Questionnaire at all ages in both samples. Results: A total of 13 546 individuals were included in the analyses. In the child cohort, mean (SD) age was 3.0 [0.01] years; 3852 (51.3%) were male participants. In the adolescent cohort, mean age was 9.0 (0.1) years; 3082 (51.0%) were male participants. Four profiles were identified in both cohorts that could be broadly labeled as no psychopathology (incidence range, 60%-70%), high psychopathology (incidence range, 3%-5%), externalizing problems (incidence range, 15%-25%), and internalizing problems (incidence range, 7%-12%). Transition between the profiles was common in both cohorts, with 3649 of 7507 participants (48.6%) in the child cohort and 2661 of 6039 participants (44.1%) in the adolescent cohort moving into 1 of the 3 psychopathology profiles at some point in development. Transition to the high psychopathology profile was most often preceded by externalizing problems. Approximately 3% to 4% of the sample had persistent psychopathology (child cohort, 203 participants [2.7%]; adolescent cohort, 216 participants [3.6%]). All psychopathology profiles were more common in boys in early life but, by late adolescence, girls were more likely to have internalizing problems. In a cross-cohort comparison at age 9, there were differences in the sex distributions of the profiles between the samples. Conclusions and Relevance: Using person-centered methods, this study demonstrated that from early life young peoples' experience of psychopathology is dynamic-they can move between different mental health problems; for most children, these problems are transient, but a small proportion (fewer than 5%) have persistent difficulties. In the context of finite resources, optimizing care requires the early identification of those with persistent phenomena.

Plasma lipid alterations in young adults with psychotic experiences: A study from the Avon Longitudinal Study of Parents and Children cohort.

BACKGROUND: Psychotic experiences (PEs) are associated with an increased risk of future psychotic and non-psychotic mental disorders. The identification of biomarkers of PEs may provide insights regarding the underlying pathophysiology. METHODS: The current study applied targeted lipidomic approaches to compare plasma lipid profiles in participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who did (n = 206) or did not (n = 206) have PEs when aged approximately 24 years. RESULTS: In total, 202 lipids including 8 lipid classes were measured by using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Eight lipid clusters were generated. Thirteen individual lipids were nominally significantly higher in the PEs group compared to the control group. After correction for multiple comparisons, 9 lipids comprising 3 lysophosphatidylcholines (LPCs), 2 phosphatidylcholines (PCs) and 4 triacylglycerols (TGs) remained significant. In addition, PEs cases had increased levels of TGs and LPCs with a low double bond count. CONCLUSIONS: These findings indicate plasma lipidomic abnormalities in individuals experiencing PEs. The lipidomic profile measures could aid our understanding of the underlying pathophysiological mechanisms.

Maternal smoking and smokeless tobacco use during pregnancy and offspring development: sibling analysis in an intergenerational Swedish cohort.

BACKGROUND: The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction. As fetal growth and cognitive development may share similar confounding structures, comparison of the two associations may improve understanding of the causal nature of the association with ID. Furthermore, comparisons of smoking with smokeless tobacco use may aid identification of mechanisms of action. METHODS: This was a cohort study of all Swedish births between 1999 and 2012 (n = 1 070 013), with prospectively recorded data. We assessed the association between maternal smoking during pregnancy and offspring outcomes ID and born small for gestational age (SGA). Analyses were repeated for snus use in pregnancy. Using a sibling design, we estimated within-family effects that control for shared sibling characteristics. RESULTS: Those exposed to maternal smoking in pregnancy had increased odds of ID [odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.16-1.33] and SGA (OR = 2.19, 95% CI: 2.11-2.27) after confounder adjustment. Within-family effects were found for SGA (OR = 1.44, 95% CI: 1.27-1.63) but not ID (OR = 0.92, 95% CI: 0.74-1.14). For snus use, the results for ID were similar to smoking. We found increased odds of offspring SGA among mothers who used snus in pregnancy in sensitivity analyses but not in primary analyses. CONCLUSIONS: Our findings are consistent with a causal effect of maternal smoking in pregnancy on risk of offspring born SGA but not on risk of ID. We found no evidence for a causal effect of snus use in pregnancy on ID and inconclusive evidence for SGA.

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence.

BACKGROUND: It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. METHODS: Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. RESULTS: The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. CONCLUSIONS: Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.