Examining the association between prenatal and perinatal adversity and the psychotic experiences in childhood.

BACKGROUND: Prenatal and perinatal complications are established risk factors for psychotic disorder, but far less is known about these measures and psychotic experiences (PEs). We investigated the longitudinal effect of prenatal risk factors (maternal behavior, medication complications) and perinatal risk factors (birth weight, medical complications) on frequency of PEs. We also examined the cumulative risk of prenatal/perinatal risk factors, and differences between transient PE, persistent PE, and controls. METHODS: The Adolescent Brain Cognitive Development study is a large child cohort (age 9-10 at baseline; n = 11 872 with PE data). PEs were measured longitudinally using the Prodromal Questionnaire-Brief, Child version, and included only if reported as distressing. Mixed-effects models were used for analysis, controlling for random effects, and a substantial number of fixed-effects covariates. RESULTS: Urinary tract infection (ß = 0.11, 95% confidence interval [CI] 0.03-0.19) and severe anemia (ß = 0.18, 95% CI 0.07-0.29) increased frequency of distressing PEs in childhood. Number of prenatal complications increased frequency of PEs (ß = 0.03, 95% CI 0.01-0.06) and risk of persistent PEs (odds ratio [OR] = 1.08, 95% CI 1.01-1.15). Maternal smoking was associated with an increased frequency of PEs (ß = 0.11, 95% CI 0.04-0.18) and persistent PEs (OR = 1.31, 95% CI 1.04-1.66). Maternal substance use was a risk factor for a 48% increased risk of persistent PEs (OR = 1.48, 95% CI 1.08-2.01). Perinatal complications showed no effect on PEs. CONCLUSIONS: This study provides evidence that certain prenatal medical complications (severe nausea, severe anemia), cumulative number of prenatal medical complications, and maternal behaviors (smoking during pregnancy), increased frequency of distressing PEs in childhood. Maternal smoking and substance use, as well as cumulative number of prenatal complications increased risk of persistent PEs.

Associations between soluble urokinase plasminogen activator receptor (suPAR) concentration and psychiatric disorders - A systematic review and meta-analysis.

BACKGROUND: There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. METHOD: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). DISCUSSION: When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.

Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms.

BACKGROUND: Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms. METHODS: We used data from participants of the North American Prodromal Longitudinal Studies (NAPLS) 2 and 3 (n = 715) who provided blood samples (Unaffected Comparison subjects (UC) n = 223 and CHR n = 483). Baseline proteomic data was quantified from plasma samples using mass spectrometry. Differential expression was examined between CHR and UC using logistic regression. Psychosocial functioning was measured using the Global Assessment of Functioning scale (GAF). Symptoms were measured using the subscale scores from the Scale of Psychosis-risk Symptoms; positive, negative, general, and disorganised. Three measures of each outcome were included: baseline, longest available follow-up (last follow-up) and most severe follow-up (MSF). Associations between the proteomic data, GAF and symptoms were assessed using ordinal regression. RESULTS: Of the 99 proteins quantified, six were differentially expressed between UC and CHR. However, only haptoglobin (HP) survived FDR-correction (OR:1.45, 95 %CI:1.23-1.69, padj = <0.001). HP was cross-sectionally and longitudinally associated with functioning and symptoms such that higher HP values were associated with poorer functioning and more severe symptoms. Results were evident after stringent adjustment and poorer functioning was observed in both NAPLS cohort separately. CONCLUSION: We demonstrate that elevated HP is robustly observed in those at CHR for psychosis, irrespective of transition to psychosis. HP is longitudinally associated with poorer functioning and greater symptom severity. These results agree with previous reports of increased HP gene expression in individuals at-risk for psychosis and with the dysfunction of the acute phase inflammatory response seen in psychotic disorders.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Evidence that infant and early childhood developmental impairments are associated with hallucinatory experiences: results from a large, population-based cohort study.

BACKGROUND: Cognitive and motor dysfunction are hallmark features of the psychosis continuum, and have been detected during late childhood and adolescence in youth who report psychotic experiences (PE). However, previous investigations have not explored infancy and early childhood development. It remains unclear whether such deficits emerge much earlier in life, and whether they are associated with psychotic, specifically hallucinatory, experiences (HE). METHODS: This study included data from Gen2 participants of The Raine Study (n = 1101), a population-based longitudinal cohort study in Western Australia. Five areas of childhood development comprising: communication; fine motor; gross motor; adaptive (problem-solving); and personal-social skills, were assessed serially at ages 1, 2 and 3 years. Information on HE, depression and anxiety at ages 10, 14 and 17 years was obtained. HE were further subdivided into those with transient or recurrent experiences. Mixed effects logistic regression models and cumulative risk analyses based on multiple domain delays were performed. RESULTS: Early poorer development in multiple areas was noted from ages 1, 2 and 3 years among youth who reported HE. Early developmental delays significantly increased the risk for later HE. This association was particularly marked in the recurrent HE group, with over 40% having early developmental delays in multiple domains. There was no significant association between early childhood development and later anxiety/depression apart from lower gross motor scores at age 3. CONCLUSIONS: The findings suggest that early pan-developmental deficits are associated with later HE, with the effect strongest for young people who report recurrent HE throughout childhood and adolescence.

Predicting childhood ADHD-linked symptoms from prenatal and perinatal data in the ABCD cohort.

This study investigates the capacity of pre/perinatal factors to predict attention-deficit/hyperactivity disorder (ADHD) symptoms in childhood. It also explores whether predictive accuracy of a pre/perinatal model varies for different groups in the population. We used the ABCD (Adolescent Brain Cognitive Development) cohort from the United States (N = 9975). Pre/perinatal information and the Child Behavior Checklist were reported by the parent when the child was aged 9-10. Forty variables which are generally known by birth were input as potential predictors including maternal substance-use, obstetric complications and child demographics. Elastic net regression with 5-fold validation was performed, and subsequently stratified by sex, race/ethnicity, household income and parental psychopathology. Seventeen pre/perinatal variables were identified as robust predictors of ADHD symptoms in this cohort. The model explained just 8.13% of the variance in ADHD symptoms on average (95% CI = 5.6%-11.5%). Predictive accuracy of the model varied significantly by subgroup, particularly across income groups, and several pre/perinatal factors appeared to be sex-specific. Results suggest we may be able to predict childhood ADHD symptoms with modest accuracy from birth. This study needs to be replicated using prospectively measured pre/perinatal data.

Investigating the effectiveness of three school based interventions for preventing psychotic experiences over a year period - a secondary data analysis study of a randomized control trial.

INTRODUCTION: Psychotic experiences (PEs) are associated with increased risk of later mental disorders and so could be valuable in prevention studies. However, to date few intervention studies have examined PEs. Given this lack of evidence, in the current study a secondary data analysis was conducted on a clustered-randomized control trial (RCT) of 3 school based interventions to reduce suicidal behaviour, to investigate if these may reduce rates of PEs, and prevent PE, at 3-month and 1-year follow-up. METHODS: The Irish site of the Saving and Empowering Young Lives in Europe study, trial registration (DRKS00000214), a cluster-RCT designed to examine the effect of school-based interventions on suicidal thoughts and behaviour. Seventeen schools (n = 1096) were randomly assigned to one of three intervention arms or a control arm. The interventions included a teacher training (gate-keeper) intervention, an interactive educational (universal-education) intervention, and a screening and integrated referral (selective-indicative) intervention. The primary outcome of this secondary data-analysis was reduction in point-prevalence of PEs at 12 months. A second analysis excluding those with PEs at baseline was conducted to examine prevention of PEs. Additional analysis was conducted of change in depression and anxiety scores (comparing those with/without PEs) in each arm of the intervention. Statistical analyses were conducted using mixed-effects modelling. RESULTS: At 12-months, the screening and referral intervention was associated with a significant reduction in PEs (OR:0.12,95%CI[0.02-0.62]) compared to the control arm. The teacher training and education intervention did not show this effect. Prevention was also observed only in the screening and referral arm (OR:0.30,95%CI[0.09-0.97]). Participants with PEs showed higher levels of depression and anxiety symptoms, compared to those without, and different responses to the screening and referral intervention & universal-education intervention. CONCLUSIONS: This study provides the first evidence for a school based intervention that reduce & prevent PEs in adolescence. This intervention is a combination of a school-based screening for psychopathology and subsequent referral intervention significantly reduced PEs in adolescents. Although further research is needed, our findings point to the effectiveness of school-based programmes for prevention of future mental health problems.

The persistent effects of foetal growth on child and adolescent mental health: longitudinal evidence from a large population-based cohort.

Low birth weight for one's gestational age is associated with higher rates of child psychopathology, however, most studies assess psychopathology cross-sectionally. The effect of such foetal growth restriction appears to be strongest for attention problems in childhood, although adult studies have found associations with a range of outcomes, from depression to psychosis. We explore how associations between foetal growth and psychopathology change across age, and whether they vary by sex. We used a large nationally representative cohort of children from Ireland (N ~ 8000). Parents completed the Strengths and Difficulties Questionnaire (SDQ) at 3 time points (age 9, 13 and 17). Outcomes included a total problems scale and subscales measuring attention/hyperactivity, peer, conduct and emotional problems. Foetal growth had significant associations with all problem scales, even after controlling for sex, socioeconomic factors and parental mental health. The magnitude of these effects was small but relatively stable across ages 9-17. In males, foetal growth had the strongest associations with attention/hyperactivity and peer problems, whereas females showed more widespread associations with all four subscales. There was a trend for the association between foetal growth and emotional problems to increase with advancing age, approaching the borderline-abnormal threshold by age 17. Reduced foetal growth predicted persistently higher scores on all measured aspects of child and adolescent psychopathology. Associations with child attention/hyperactivity may generalize to a wider array of adult psychopathologies via adolescent-onset emotional problems. Future studies should explore potential age-dependent effects of foetal growth into the early 20s.

The inter-relatedness and demographic predictors of physical activity, self-rated health, and mental well-being: A three-wave study in secondary school children.

INTRODUCTION: The World Health Organisation recommends that children and adolescents engage in at least 60 min of moderate-to-vigorous physical activity per day. Previous research has shown that physical activity is related to other constructs such as mental well-being and self-rated health. This study examined the inter-relatedness of these constructs in Northern Irish school children. METHODS: This study was a secondary analysis of data gathered as part of a longitudinal study. Participants were n = 1791 adolescents in their final years of secondary (high) school (age range 15-18; female = 64.6%). Data were gathered on three occasions over a 2-year period on self-rated health, physical activity, mental well-being, heavy episodic drinking, lifetime smoking, psychological and somatic symptoms, as well as a range of socio-demographic measures. RESULTS: Descriptive results showed extremely low levels of self-reported physical activity within the past week, with <6% of the sample attaining the WHO guidelines at each wave of data collection. There were significant gender differences on all variables assessed. Results further showed a small-sized relationship (statistically significant for girls only) between physical activity and mental well-being. There was also a small-sized relationship between physical activity and self-rated health. Notably, effect sizes for the relationship between self-rated health and both physical activity and mental well-being were higher. In terms of socio-demographic predictors of lower physical activity, being female, lifetime cigarette smoking, and higher somatic and psychological symptoms were all statistically significant factors. CONCLUSION: Self-rated health emerged as the most important predictor of physical activity among adolescents.

Medical students, mental health and the role of resilience - A cross-sectional study.

BACKGROUND: Medical students have reported high prevalence of mental health difficulties and burnout. However, there are limited investigations examining the association between resilience and these difficulties. We investigated: (1) depression, anxiety, personal and professional burnout, and comorbidity; (2) demographic and education characteristics associated with these outcomes; (3) the association between resilience and these outcomes; and (4) whether these results were attributable to sampling bias. METHODS: Participants were n = 521 medical students from RCSI University of Medicine and Health Sciences. Outcomes were measured using validated scales. We report descriptive statistics, and risk factors for the difficulties were investigated using generalized linear modelling. RESULTS: One-in-three students reported incidence of depression or anxiety (24.5% co-morbidity). 8.9% of students reported all four difficulties. Difficulties were more common in female students and those in middle years of the programme. Resilience was negatively correlated with all outcomes and stable across demographic and educational variables. Weighting the data for sampling bias did not affect these results. CONCLUSIONS: Our results emphasise the high incidence of depression, anxiety, burnout, and comorbidity in students. We advocate for further investigation into the role of resilience as a modifiable factor that may ameliorate the incidence of depression, anxiety, and burnout in medical students.

Psychotic experiences in the general population, a review; definition, risk factors, outcomes and interventions.

Psychotic experiences (PE) are common in the general population, in particular in childhood, adolescence and young adulthood. PE have been shown to be associated with an increased risk for later psychotic disorders, mental disorders, and poorer functioning. Recent findings have highlighted the relevance of PE to many fields of healthcare, including treatment response in clinical services for anxiety & depression treatment, healthcare costs and service use. Despite PE relevance to many areas of mental health, and healthcare research, there remains a gap of information between PE researchers and experts in other fields. With this review, we aim to bridge this gap by providing a broad overview of the current state of PE research, and future directions. This narrative review aims to provide an broad overview of the literature on psychotic experiences, under the following headings: (1) Definition and Measurement of PE; (2) Risk Factors for PE; (3) PE and Health; (4) PE and Psychosocial Functioning; (5) Interventions for PE, (6) Future Directions.

The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial.

BACKGROUND: There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.

Machine learning based prediction and the influence of complement - Coagulation pathway proteins on clinical outcome: Results from the NEURAPRO trial.

BACKGROUND: Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR. MATERIALS AND METHODS: We carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome. RESULTS AND CONCLUSION: A prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients.

Mediators of the longitudinal relationship between childhood adversity and late adolescent psychopathology.

BACKGROUND: Childhood adversity (CA) is commonly associated with an increased risk of subsequent psychopathology. It is important to identify potential mediators of this relationship which can allow for the development of interventions. In a large population-based cohort study we investigated the relationship between CA and late adolescent psychopathology and early adolescent candidate mediators of this relationship. METHODS: We used data from three waves (n = 6039) of Cohort 98' of the Growing up in Ireland Study (age 9, 13 and 17). We used doubly robust counterfactual analyses to investigate the relationship between CA (reported at age-9) with psychopathology (internalizing and externalizing problems), measured using the Strengths and Difficulties Questionnaire at age-17. Counterfactual and traditional mediation was used to investigate the mediating effects of the parent-child relationship, peer relations, self-concept, computer usage and physical activity. RESULTS: CA was associated with an increased risk of internalizing and externalizing problems at age-17. Parent-child conflict mediated 35 and 42% of the relationship between CA and late adolescent externalizing problems and internalizing problems, respectively. Self-concept and physical activity mediated an additional proportion of the relationship between CA and internalizing problems. These results were robust to unmeasured confounding. CONCLUSIONS: Parent-child conflict explains more than a third of the relationship between CA and later psychopathology. Self-concept and physical activity explain the additional proportion of the relationship between CA and internalizing problems. This suggests that these factors may be good targets for intervention in young people who have experienced CA to prevent subsequent psychopathology.

Intelligence quotient decline following frequent or dependent cannabis use in youth: a systematic review and meta-analysis of longitudinal studies.

Previous systematic reviews and meta-analyses of cross-sectional data assessing the effect of cannabis on cognitive functioning and intelligence show inconsistent results. We hypothesized that frequent and dependent cannabis use in youth would be associated with Intelligence Quotient (IQ) decline. This study is a systematic review and meta-analysis. We searched Embase, PubMed and PsychInfo from inception to 24 January 2020. We included studies with non-treatment seeking samples and pre- and post-exposure measures of IQ. We requested data from authors if summary data was not available from published work. We preregistered our review with PROSPERO (ID no. CRD42019125624). We found seven cohort studies including 808 cases and 5308 controls. We found a significant effect for the association between frequent or dependent cannabis use in youth and IQ change, Cohen's d = -0.132 (95% CI -0.198 to -0.066) p < 0.001. Statistical heterogeneity between studies was also low at I2 = 0.2%. Study quality was moderate to high. This translates to an average decline of approximately 2 IQ points following exposure to cannabis in youth. Future studies should have longer periods of follow up to assess the magnitude of developmental impact.

Risk and protective factors for psychotic experiences in adolescence: a population-based study.

BACKGROUND: Psychotic experiences (PEs) are reported by a significant minority of adolescents and are associated with the development of psychiatric disorders. The aims of this study were to examine associations between PEs and a range of factors including psychopathology, adversity and lifestyle, and to investigate mediating effects of coping style and parental support on associations between adversity and PEs in a general population adolescent sample. METHOD: Cross-sectional data were drawn from the Irish centre of the Saving and Empowering Young Lives in Europe study. Students completed a self-report questionnaire and 973 adolescents, of whom 522 (53.6%) were boys, participated. PEs were assessed using the 7-item Adolescent Psychotic Symptom Screener. RESULTS: Of the total sample, 81 (8.7%) of the sample were found to be at risk of PEs. In multivariate analysis, associations were found between PEs and number of adverse events reported (OR 4.48, CI 1.41-14.25; p < 0.011), maladaptive/pathological internet use (OR 2.70, CI 1.30-5.58; p = 0.007), alcohol intoxication (OR 2.12, CI 1.10-4.12; p = 0.025) and anxiety symptoms (OR 4.03, CI 1.57-10.33; p = 0.004). There were small mediating effects of parental supervision, parental support and maladaptive coping on associations between adversity and PEs. CONCLUSION: We have identified potential risk factors for PEs from multiple domains including adversity, mental health and lifestyle factors. The mediating effect of parental support on associations between adversity and PEs suggests that poor family relationships may account for some of this mechanism. These findings can inform the development of interventions for adolescents at risk.

Early adult mental health, functional and neuropsychological outcomes of young people who have reported psychotic experiences: a 10-year longitudinal study.

BACKGROUND: Psychotic experiences (PE) are highly prevalent in childhood and are known to be associated with co-morbid mental health disorders and functional difficulties in adolescence. However, little is known about the long-term outcomes of young people who report PE. METHODS: As part of the Adolescent Brain Development Study, 211 young people were recruited in childhood (mean age 11.7 years) and underwent detailed clinical interviews, with 25% reporting PE. A 10 year follow-up study was completed and 103 participants returned (mean age 20.9 years). Structured clinical interviews for DSM-5 (SCID-5) and interviewer-rated assessments of functioning were conducted. A detailed neuropsychological battery was also administered. Analyses investigated group differences between those who had ever reported PE and controls in early adulthood. RESULTS: The PE group was at a significantly higher risk of meeting DSM-5 criteria for a current (OR 4.08, CI 1.16-14.29, p = 0.03) and lifetime psychiatric disorder (OR 3.27, CI 1.43-7.47, p = 0.005). They were also at a significantly higher risk of multi-morbid lifetime psychiatric disorders. Significantly lower scores on current social and global functioning measures were observed for the PE group. Overall, there were no differences in neuropsychological performance between groups apart from significantly lower scores on the Stroop Word task and the Purdue Pegboard task for the PE group. CONCLUSIONS: Our findings suggest that reports of PE are associated with poorer mental health and functional outcomes in early adulthood, with some persisting cognitive and motor deficits. Young people who report such symptoms could be considered a target group for interventions to aid functional outcomes.

A meta-analysis of the relationship between parental death in childhood and subsequent psychiatric disorder.

OBJECTIVE: To systematically review evidence for an association between parental death in childhood, and the subsequent development of an anxiety, affective or psychotic disorder. METHODS: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, cohort studies in the English language. Meta-analyses were performed for studies reporting hazard ratios, incidence rate ratios and odds ratios. Two studies reported risk ratios, and these were included in an overall pool of odds, risk and incidence rate ratios. Sensitivity analyses were performed (removal of one study at a time) for all meta-analyses, and study quality assessed using the Newcastle-Ottawa Scale. RESULTS: Fifteen studies were retained, and where required, data were averaged in advance of pooling. Significant results were observed in studies reporting hazard ratios (k = 4, 1.48 [95% CI = 1.32-1.66]), incidence rate ratios (k = 3, 1.37 [95% CI = 1.01-1.85]), but not odds ratios (k = 4, 0.87 [95% CI = 0.72, 1.05]). However, the overall pooled effect (using odds, incidence rate and risk ratios) was statistically significant (k = 9, 1.22 [95% CI = 1.03-1.44]). CONCLUSION: Overall, the evidence suggests that there is a positive association between the death of a parent before age 18, and the subsequent development of an anxiety, affective or psychotic disorder. The lack of a significant pooled effect in studies reporting results as odds ratios is likely an artefact of study design. LIMITATIONS: Data were clustered in four countries making generalizability uncertain. Studies adjusted for a variety of possible confounders, and follow-up after death varied considerably.

Childhood trauma and adult mental disorder: A systematic review and meta-analysis of longitudinal cohort studies.

OBJECTIVE: To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood. METHODS: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained. RESULTS: Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed. CONCLUSION: There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.

Self-reported interpersonal and educational/vocational difficulties in young adults with a history of transient psychotic experiences: findings from a population-based study.

BACKGROUND: Psychotic experiences (PEs) are not uncommon in young people and are associated with both psychopathology and compromised global functioning. Although psychotic experiences are transient (short-lived, self-resolving and non-recurring) for most people who report them, few studies have examined the association between early transient PEs and later functioning in population samples. Additionally, studies using self-report measures of interpersonal and educational/ vocational difficulties are lacking. The aim of this study was to examine the relationship between transient psychotic experiences and self-reported interpersonal and educational/vocational difficulties in adolescence and young adulthood. METHODS: Participants were 103 young people from a longitudinal population-based study cohort of mental health in Ireland. They attended for baseline clinical interviews in childhood (age 11-13) and were followed up in young adulthood (age 19-25). Participants who reported psychotic experiences at baseline but not at follow-up were classified as having transient psychotic experiences. Data from both time-points were used to examine the association between transient psychotic experiences and self-reported interpersonal and educational/ vocational difficulties in young adulthood using poisson regression modelling. RESULTS: Young people with a history of transient psychotic experiences reported significantly higher interpersonal (adj IRR: 1.83, 95%ileCI: 1.10-3.02, p = .02) and educational/vocational (adj IRR: 2.28, 95%ileCI: 1.43-3.64, p = .001) difficulties during adolescence. However, no significant differences in interpersonal (adj IRR: 0.49, 95%ileCI: 0.10-2.30, p = .37) or educational/vocational (adj IRR: 0.88, 95%ileCI: 0.37-2.08, p = .77) difficulties were found in young adulthood. Self-reported interpersonal and educational/vocational difficulties in young people both with and without a history of transient psychotic experiences decreased between adolescence and young adulthood. CONCLUSIONS: Young people with transient psychotic experiences have increased interpersonal and educational/vocational difficulties in adolescence but these may not persist into the young adult years. This finding indicates that early psychotic experiences may not confer high risk for long-term interpersonal or educational/vocational deficits among young people who experience these phenomena transiently.