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.

Longitudinal Trajectories of Plasma Polyunsaturated Fatty Acids and Associations With Psychosis Spectrum Outcomes in Early Adulthood.

BACKGROUND: Evidence supports associations between polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and psychosis. However, polyunsaturated fatty acid trajectories in the general population have not been characterized, and associations with psychosis spectrum outcomes in early adulthood are unknown. METHODS: Plasma omega-6 to omega-3 ratio and DHA (expressed as percentage of total fatty acids) were measured by nuclear magnetic spectroscopy at 7, 15, 17, and 24 years of age in participants of ALSPAC (Avon Longitudinal Study of Parents and Children). Curvilinear growth mixture modeling evaluated body mass index-adjusted trajectories of both measures. Outcomes were assessed at 24 years. Psychotic experiences (PEs), at-risk mental state status, psychotic disorder, and number of PEs were assessed using the Psychosis-Like Symptoms interview (n = 3635; 2247 [61.8%] female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n = 3484; 2161 [62.0%] female). Associations were adjusted for sex, ethnicity, parental social class, and cumulative smoking and alcohol use. RESULTS: Relative to stable average, the persistently high omega-6 to omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio [aOR] = 1.63, 95% CI = 0.92-2.89; psychotic disorder aOR = 1.69, 95% CI = 0.71-4.07). This was also the case for persistently low DHA (PEs aOR = 1.42, 95% CI = 0.84-2.37; psychotic disorder aOR = 1.14, 95% CI = 0.49-2.67). Following adjustment, persistently high omega-6 to omega-3 ratio was associated with increased number of PEs (ß = 0.41, 95% CI = 0.05-0.78) and negative symptoms score (ß = 0.43, 95% CI = 0.14-0.72), as was persistently low DHA (number of PEs ß = 0.45, 95% CI = 0.14-0.76; negative symptoms ß = 0.35, 95% CI = 0.12-0.58). CONCLUSIONS: Optimization of polyunsaturated fatty acid status during development warrants further investigation in relation to psychotic symptoms in early adulthood.

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.

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.

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.

Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study.

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

Longitudinal hippocampal subfield development associated with psychotic experiences in young people.

Hippocampal volumetric reductions are observed across the psychosis spectrum, with interest in the localisation of these reductions within the hippocampal subfields increasing. Deficits of the CA1 subfield in particular have been implicated in the neuropathophysiology of psychotic disorders. Investigating the trajectory of these abnormalities in healthy adolescents reporting sub-threshold psychotic experiences (PE) can provide insight into the neural mechanisms underlying psychotic symptoms without the potentially confounding effects of a formal disorder, or antipsychotic medication. In this novel investigation, a sample of 211 young people aged 11-13 participated initially in the Adolescent Brain Development study. PE classification was determined by expert consensus at each timepoint. Participants underwent neuroimaging at 3 timepoints, over 6 years. 78 participants with at least one scan were included in the final sample; 33 who met criteria for a definite PE at least once across all the timepoints (PE group), and 45 controls. Data from bilateral subfields of interest (CA1, CA2/3, CA4/DG, presubiculum and subiculum) were extracted for Linear Mixed Effects analyses. Before correction, subfield volumes were found to increase in the control group and decrease in the PE group for the right CA2 and CA2/3 subfields, with moderate to large effect sizes (d = -0.61, and d = -0.79, respectively). Before correction, right subiculum and left presubiculum volumes were reduced in the PE group compared to controls, regardless of time, with moderate effect sizes (d = -0.52, and d = -0.59, respectively). However, none of these effects survived correction. Severity of symptoms were not associated with any of the noted subfields. These findings provide novel insight to the discussion of the role of hippocampal subfield abnormalities in the pathophysiology underlying psychotic experiences.

Prognostic models predicting transition to psychotic disorder using blood-based biomarkers: a systematic review and critical appraisal.

Accumulating evidence suggests individuals with psychotic disorder show abnormalities in metabolic and inflammatory processes. Recently, several studies have employed blood-based predictors in models predicting transition to psychotic disorder in risk-enriched populations. A systematic review of the performance and methodology of prognostic models using blood-based biomarkers in the prediction of psychotic disorder from risk-enriched populations is warranted. Databases (PubMed, EMBASE and PsycINFO) were searched for eligible texts from 1998 to 15/05/2023, which detailed model development or validation studies. The checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) was used to guide data extraction from eligible texts and the Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias and applicability of the studies. A narrative synthesis of the included studies was performed. Seventeen eligible studies were identified: 16 eligible model development studies and one eligible model validation study. A wide range of biomarkers were assessed, including nucleic acids, proteins, metabolites, and lipids. The range of C-index (area under the curve) estimates reported for the models was 0.67-1.00. No studies assessed model calibration. According to PROBAST criteria, all studies were at high risk of bias in the analysis domain. While a wide range of potentially predictive biomarkers were identified in the included studies, most studies did not account for overfitting in model performance estimates, no studies assessed calibration, and all models were at high risk of bias according to PROBAST criteria. External validation of the models is needed to provide more accurate estimates of their performance. Future studies which follow the latest available methodological and reporting guidelines and adopt strategies to accommodate required sample sizes for model development or validation will clarify the value of including blood-based biomarkers in models predicting psychosis.

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.

Incidence and Persistence of Psychotic Experiences in the General Population: Systematic Review and Meta-Analysis.

BACKGROUND AND HYPOTHESIS: Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention research. We sought to systematically determine the incidence and persistence of PEs in the general population. STUDY DESIGN: A double-blind search of databases (Embase, Pubmed PMC, Psychinfo, Medline, and Web of Science) from inception to January 2023 and data extraction, were conducted. Study quality was assessed using the NIH assessment tool. Random effects models were conducted to calculate pooled incidence rate per person-year and proportion of persistent PEs per year. Age and study design were all examined using subgroup analyses. Demographic, risk factors, and outcomes for incidence and persistence of PEs were reported in a narrative synthesis. STUDY RESULTS: Using a double-blind screening method for abstract (k = 5763) and full text (k = 250) were screened. In total 91 samples from 71 studies were included, of which 39 were included in a meta-analysis (incidence: k = 17, n = 56 089; persistence: k = 22, n = 81 847). Incidence rate was 0.023 per person-year (95% CI [0.0129;0.0322]). That is, for every 100 people, 2 reported first onset PEs in a year. This was highest in adolescence at 5 per 100(13-17 years). The pooled persistence rate for PEs was 31.0% (95% CI [26.65,35.35]) This was highest in adolescence at 35.8%. Cannabis was particularly associated with incidence of PEs, and persistence of PEs were associated with multiple mental disorders. CONCLUSIONS: Each year incidence of PEs is 2 of every 100 people, and persists each year in 31% of cases, this risk is highest in adolescents.

Longitudinal Gray Matter Development Associated With Psychotic Experiences in Young People.

Background: Gray matter abnormalities are observed across the psychosis spectrum. The trajectory of these abnormalities in healthy adolescents reporting subthreshold psychotic experiences (PEs) may provide insight into the neural mechanisms underlying psychotic symptoms. The risk of psychosis and additional psychopathology is even higher among these individuals who also report childhood adversity/DSM-5 diagnoses. Thus, the aims of this longitudinal study were to investigate PE-related volumetric changes in young people, noting any effects of childhood adversity/DSM-5 diagnosis. Methods: A total of 211 young people 11 to 13 years of age participated in the initial Adolescent Brain Development study. PE classification was determined by expert consensus at each time point. Participants underwent neuroimaging at 3 time points over 6 years. A total of 76 participants with at least one scan were included in the final sample; 34 who met criteria for PEs at least once across all the time points (PE group) and 42 control subjects. Data from 20 bilateral regions of interest were extracted for linear mixed-effects analyses. Results: Right hippocampal volume increased over time in the control group, with no increase in the PE group (p = .00352). DSM-5 diagnosis and childhood adversity were not significantly associated with right hippocampal volume. There was no significant effect of group or interaction in any other region. Conclusions: These findings further implicate right hippocampal volumetric abnormalities in the pathophysiology underlying PEs. Furthermore, as suggested by previous studies in those at clinical high risk for psychosis and those with first-episode psychosis, it is possible that these deficits may be a marker for later clinical outcomes.

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 association between transient childhood psychotic experiences and psychosocial outcomes in young adulthood: Examining the role of mental disorders and adult attachment.

AIM: Evidence suggest individuals with mental disorders and psychotic experiences (PE), even transient PE, show poorer psychosocial outcomes relative to those with mental disorders. The concept of "attachment" is hypothesized as the mechanism by which people seek support in times of need. This can be measured as discrete styles or as positive (low avoidance/anxiety)/negative (high avoidance/anxiety) dimensions. Adult attachment has previously been examined on PE risk factors, but not outcomes. This study aimed to examine the relationship between transient childhood PE and adult psychosocial outcomes, comparing those with and without mental disorders. Second, to examine the role of adult attachment. METHOD: Participants (n = 103) attended baseline (age 11-13) and 10-year follow-up. PE and mental disorders were measured using the Schedule for Affective Disorders and Schizophrenia for School-aged Children. Attachment and outcomes were measured using self-report measures. Analysis compared those with PE (with/without mental disorders), and mental disorders without PE, to controls, using linear and Poisson regression. RESULTS: PE was associated with lower self-esteem (ß = -2.28, p = .03), perceived social support from friends (ß = -2.80, p = .01), and higher stress in platonic relationships (IRR = 1.64). PE and mental disorders were associated with lower self-esteem (ß = -5.74, p = .002), higher stress in romantic (IRR = 1.40) and platonic (IRR = 1.59) relationships, general stress (ß = 5.60, p = .006), and mental distress (ß = 5.67, p = .001). Mental disorders alone was not associated with any measure. Adult attachment dimensions attenuated some results. CONCLUSIONS: This paper illustrates the association between transient PE and adult psychosocial outcomes, with & without co-occurring mental disorders, and demonstrates the role of adult attachment.

Explaining the Association Between Fetal Growth and Childhood ADHD Symptoms: Cross-cohort Replication.

The association between restricted fetal growth and symptoms of attention deficit/hyperactivity disorder (ADHD) in childhood is well-replicated and robust. However, fetal growth is determined by many prenatal factors and associations with mental health may be confounded by familial and social context. In this study, we sought to quantify the relative contributions of prenatal factors and familial confounds to the association between fetal growth and ADHD symptoms. Two independent cohorts were analyzed, the Adolescent Brain Cognitive Development study (ABCD; United States) and the Growing Up in Ireland (GUI) study. ADHD symptoms were measured by the Child Behavior Checklist (ABCD) and the Strengths & Difficulties questionnaire (GUI) at age 9-10. Using sequential regression models, we assessed the change-in-association between fetal growth and ADHD symptoms after controlling for sex, familial factors (socioeconomic/demographic factors & family psychiatric history) and prenatal factors (pregnancy complications & maternal substance-use during pregnancy). Converging findings from cohorts suggested that over a quarter of the association between fetal growth and ADHD symptoms is attributable to familial confounds. The degree to which the association was explained by prenatal factors differed by cohort-pregnancy complications explained a larger proportion of the effect in ABCD (7.9%) than GUI (2.7%), and maternal substance-use explained a larger proportion of the effect in GUI (22.7%) compared to ABCD (4.8%). Different explanations of the fetal growth-ADHD association across cohorts suggests cohort-specific, and potentially nationally-specific, risk factors for fetal growth and related neurodevelopmental outcomes. The evidence suggests early prevention of ADHD in Ireland should focus on minimizing maternal smoking during pregnancy. In the US, prevention and treatment of pregnancy complications are highlighted as viable targets for intervention.

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.

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.