MYB insufficiency disrupts proteostasis in hematopoietic stem cells, leading to age-related neoplasia.

MYB plays a key role in gene regulation throughout the hematopoietic hierarchy and is critical for the maintenance of normal hematopoietic stem cells (HSC). Acquired genetic dysregulation of MYB is involved in the etiology of a number of leukemias, although inherited noncoding variants of the MYB gene are a susceptibility factor for many hematological conditions, including myeloproliferative neoplasms (MPN). The mechanisms that connect variations in MYB levels to disease predisposition, especially concerning age dependency in disease initiation, are completely unknown. Here, we describe a model of Myb insufficiency in mice that leads to MPN, myelodysplasia, and leukemia in later life, mirroring the age profile of equivalent human diseases. We show that this age dependency is intrinsic to HSC, involving a combination of an initial defective cellular state resulting from small effects on the expression of multiple genes and a progressive accumulation of further subtle changes. Similar to previous studies showing the importance of proteostasis in HSC maintenance, we observed altered proteasomal activity and elevated proliferation indicators, followed by elevated ribosome activity in young Myb-insufficient mice. We propose that these alterations combine to cause an imbalance in proteostasis, potentially creating a cellular milieu favoring disease initiation.

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.

Comparing times of self-harm presentations to hospital emergency departments in children, adolescents, young adults and adults: a national registry study 2007-2019.

PURPOSE: The few studies that have explored self-harm presentation times at hospital emergency departments (EDs) - an important factor that can determine if a patient receives a mental health assessment - primarily focus on adult samples. This study examined the times of self-harm presentations to EDs, self-harm methods used, mental health assessments, and admission data across different age-groups. METHODS: Using data from the National Self-Harm Registry Ireland over a 13-year timeframe (2007-2019), this study compared times, days, seasons, methods of self-harm, and admission data for children (8-12 years), adolescents (13-17 years), young adults (18-25 years) and adults (> 25 years). RESULTS: The majority of the 152,474 self-harm presentations (78.6%) for all ages occurred out-of-hours (outside the standard working hours or in-hours times of 09:00-17:00, Monday-Friday). The four hours before midnight had the highest proportions of self-harm presentations for adolescents (27.9%) and adults (23.1%), whereas the four hours after midnight had the highest proportion of self-harm presentations for young adults (22.9%). The 16:00-midnight timeframe had highest proportion of self-harm presentations in children (52.3%). Higher proportions of patients received a mental health assessment in-hours compared to out-of-hours among young adults (78.2% vs. 73.3%) and adults (76.1% vs. 72.0%). Self-harm presentations were lowest during summer months in children and adolescents. DISCUSSION: Hospitals should ensure that adequate resources are available for individuals presenting with self-harm, especially in the case of overcrowded EDs, and protocols need to be designed for those presenting with self-harm due to intoxication. In line with national policy, protocols for patients presenting during out-of-hours should be designed that can incorporate services from allied health multidisciplinary teams, social work, addiction services and counselling organisations. Given the lower rates of self-harm during school holidays for children and adolescents, the school environment must be considered in the context of mental health and self-harm public health prevention interventions.

Pregnancy complications and childhood mental health: is the association modified by sex or adverse social circumstances? Findings from the 'growing up in Ireland' national infant cohort study.

Specific pregnancy complications, socioeconomic position and sex have all been independently associated with child mental health outcomes, but their combined effects remain unclear. We examined whether total number of complications experienced in the pregnancy associated with mental health at 5 and 9-years, and whether this varied by sex or adverse social circumstances. Pregnancy complications were self-reported at 9-months post-natally from a list of 16 complications. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when their child was 5 and 9-years. The primary outcome was the SDQ-total and scoring in the clinical range (> 16) was a secondary outcome. We applied generalized linear mixed models to a large nationally representative Irish cohort (GUI; n = 11,134). Analyses were adjusted for sex, adverse social circumstances (at 9-months), and gestational smoking. We included an interaction term between pregnancy complications and each variable respectively in separate models to examine if associations varied by sex or adverse circumstances.After controlling for covariates, total complications associated with mental health at 5 and 9-years. Each additional pregnancy complication conferred a 10% higher total-SDQ score (exponentiated co-efficient 1.10 [95%CI 1.06-1.14], 1.20 [1.15-1.26], 1.20 [1.12-1.29] and 1.34 [1.21-1.48] for 1, 2, 3 and 4 + complications respectively). For the dichotomised outcome, generally increasing odds for clinical levels of mental health difficulties were observed (OR 1complication = 1.89, 95%CI [1.37-2.59]; OR 2complications = 2.31, 95%CI [1.53-3.50]; OR 3complications = 1.77, 95%CI [0.89-3.52]; OR 4 + complications = 6.88, 95%CI [3.29-14.40]). Females had significantly lower odds of exhibiting clinically significant mental health difficulties than males (OR = 0.43, 95%CI[0.32-0.57]).There was no evidence that the association between pregnancy complications and child's mental health varied by sex or social circumstances at 5 or 9-years. Males exposed to numerous pregnancy complications in the context of adverse social circumstances had the highest predicted probability of having mental health difficulties in middle childhood.

MYB as a Critical Transcription Factor and Potential Therapeutic Target in AML.

Myb was identified over four decades ago as the transforming component of acute leukemia viruses in chickens. Since then it has become increasingly apparent that dysregulated MYB activity characterizes many blood cancers, including acute myeloid leukemia, and that it represents the most "addictive" oncoprotein in many, if not all, such diseases. As a consequence of this tumor-specific dependency for MYB, it has become a major focus of efforts to develop specific antileukemia drugs. Much attention is being given to ways to interrupt the interaction between MYB and cooperating factors, in particular EP300/KAT3B and CBP/KAT3A. Aside from candidates identified through screening of small molecules, the most exciting prospect for novel drugs seems to be the design of peptide mimetics that interfere directly at the interface between MYB and its cofactors. Such peptides combine a high degree of target specificity with good efficacy including minimal effects on normal hematopoietic cells.

Debate: CAMHS will be at the forefront of the next generation of psychosis risk models, but further integration with early intervention psychosis services is needed to realise this potential: Re Debate: Prevention of psychosis in adolescents - does CAMHS have a role?

The detection of psychosis and its prodrome have unique considerations in a child and adolescent population. Young people attending CAMHS are already a high-risk group, which confers significant limitations in applying the current clinical high-risk (CHR) model. This has catalysed calls for a transdiagnostic approach to psychosis risk prediction, but without a clear pathway forward. We contribute to the debate opened by Salazar de Pablo and Arango (2023, Child and Adolescent Mental Health) on the role of CAMHS in this initiative. CAMHS have a key role in developing comprehensive longitudinal datasets to inform risk models. Closer integration with early intervention in psychosis (EIP) services will be needed to realise this potential. This integration is also required to reliably detect prodromes and emerging psychosis in young people. Where there is robust evidence to support prevention initiatives, we should proceed with their implementation, even in the absence of enhanced risk models.

Risk of first-episode psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is an established risk factor for developing a psychotic disorder in countries with a long history of migration. Less is known for countries with only a recent history of migration. This study aimed to determine the risk for developing a psychotic disorder in migrants to the Republic of Ireland. METHODS: We included all presentations of first-episode psychosis over 8.5 years to the DETECT Early Intervention for psychosis service in the Republic of Ireland (573 individuals aged 18-65, of whom 22% were first-generation migrants). Psychotic disorder diagnosis relied on SCID. The at-risk population was calculated using census data, and negative binomial regression was used to estimate incidence rate ratios. RESULTS: The annual crude incidence rate for a first-episode psychotic disorder in the total cohort was 25.62 per 100000 population at risk. Migrants from Africa had a nearly twofold increased risk for developing a psychotic disorder compared to those born in the Republic of Ireland (IRR = 1.83, 95% CI 1.11-3.02, p = 0.02). In contrast, migrants from certain Asian countries had a reduced risk, specifically those from China, India, Philippines, Pakistan, Malaysia, Bangladesh and Hong Kong (aIRR = 0.36, 95% CI 0.16-0.81, p = 0.01). CONCLUSIONS: Further research into the reasons for this inflated risk in specific migrant groups could produce insights into the aetiology of psychotic disorders. This information should also be used, alongside other data on environmental risk factors that can be determined from census data, to predict the incidence of psychotic disorders and thereby resource services appropriately.

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.

Time of self-harm presentations to hospital emergency departments: a scoping review.

BACKGROUND: The time at which a self-harm presentation occurs has been shown to be a significant factor as to whether a patient receives a psychiatric assessment or not, which may benefit the patient's future care. This scoping review sought to identify studies that report on the peak time of day for self-harm presentations to hospital Emergency Departments (EDs). This could help hospital managers to properly allocate the appropriate services for self-harm patients when they are needed the most. METHODS: A scoping review of the literature from the year 2000 until 30th June 2021 was carried out using the PubMed, Web of Science, Embase and the Cochrane library databases. RESULTS: There were 22 studies that were included for data extraction. The findings from 20 of these studies indicate that self-harm presentations tend to occur outside of working hours (09:00-17:00, Monday to Friday). The majority of studies found that the peak time for self-harm presentations was in the hours before and after midnight. CONCLUSIONS: While this scoping review identified a satisfactory number of studies for data extraction, examination of time of day of presentation was a secondary outcome across most studies. Given that the majority of studies focused on adult samples, further research is necessary to investigate peak times for other age cohorts. More research on this topic is also needed in low- and middle-income countries. Consideration should be given to ensure that the necessary resources to treat hospital presenting self-harm are allocated outside of typical working hours.

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.

Microstructural changes along the cingulum in young adolescents with psychotic experiences: An along-tract analysis.

Psychotic experiences (PEs) such as hallucinations and delusions are common among young people without psychiatric diagnoses and are associated with connectivity and white matter abnormalities, particularly in the limbic system. Using diffusion magnetic resonance imaging (MRI) in adolescents with reported PEs and matched controls, we examined the cingulum white matter tract along its length rather than as the usually reported single indivisible structure. Complex regional differences in diffusion metrics were found along the bundle at key loci following Bonferroni significance adjustment (p < .00013) with moderate to large effect sizes (.11-.76) throughout all significant subsegments. In this prospective community-based cohort of school-age children, these findings suggest that white matter alterations in the limbic system may be more common in the general non-clinical adolescent population than previously thought. Such white matter alternations may only be uncovered using a similar more granular along-tract analysis of white matter tracts.

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.

Upper Esophageal Sphincter Compression Device as an Adjunct to Proton Pump Inhibition for Laryngopharyngeal Reflux.

BACKGROUND: The Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR). METHODS: This two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI. RESULTS: Thirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p < 0.01). Compared to non-responders, responders to Device + PPI had a significantly lower BMI (p = 0.02) and higher salivary pepsin concentration (p = 0.01). CONCLUSION: This clinical trial highlights the potential efficacy of the external UES compression device (Reflux Band) as an adjunct to PPI for patients with LPR (ClinicalTrials.Gov NCT03619811).

Maternal smoking during pregnancy and offspring psychiatric disorder: a longitudinal birth cohort study.

BACKGROUND: There is evidence that prenatal stress and smoking during pregnancy both independently increase the risk of offspring psychopathology. Here we examine whether increased levels of self-reported stress is associated with increased smoking in a population of pregnant women, and whether prenatal smoking is associated with offspring psychiatric diagnoses independent of prenatal stress exposure. METHOD: Using a longitudinal birth cohort, we used ordered logistic regressions to examine associations between maternal stress and smoking during pregnancy. We then used logistic regression analyses to examine associations between prenatal smoking and later offspring psychiatric disorders. RESULTS: A dose-response relationship was found between maternally reported stress and smoking during pregnancy. Pregnant women reporting severe stress were more likely to smoke compared to both the moderate stress and no stress groups, and those reporting moderate stress were significantly more likely to smoke compared to the no stress group. Smoking more than 5 cigarettes daily during pregnancy increased the risk of offspring personality disorder (OR 3.08, 95% CI 1.60-5.94) as well as developing any Axis 1 psychiatric disorder, inclusive of mood, anxiety and psychotic disorders (OR 1.45, 95% CI 1.04-2.04). After adjusting for parental psychiatric history and maternal self-reported stress during pregnancy, associations between smoking more than 5 cigarettes daily when pregnancy and offspring personality (OR 2.58 95% CI 1.32-5.06) disorder remained. CONCLUSION: Exposure to cigarette smoking during gestation could impact a child's mental health. Smoking during pregnancy is a prime target for preventative interventions as unlike most other environmental risk factors, it is very amenable to change.

A qualitative study exploring personal recovery meaning and the potential influence of clinical recovery status on this meaning 20 years after a first-episode psychosis.

PURPOSE: Long-term data on recovery conceptualisation in psychotic illness are needed to support mental health services to organise themselves according to recovery-oriented frameworks. To our knowledge, no previous research has investigated how first-episode psychosis (FEP) service users (sampled across psychotic illness type) perceive recovery beyond 5 years after diagnosis. We aimed to explore personal recovery meaning with individuals 20 years after their FEP and examine the potential influence of clinical recovery status on how they defined recovery (i.e. personal recovery). METHODS: Twenty participants were purposefully sampled from an epidemiologically representative FEP incidence cohort. At 20-year follow-up, semi-structured interviews were conducted with 10 cohort members who met full 'functional recovery criteria' (Clinically Recovered Group) and 10 who did not (Not Clinically Recovered Group). A thematic analysis was performed to develop shared themes and group-specific sub-themes to capture agreement and divergence between groups. RESULTS: Five shared themes were produced: pursuing balance in conflict, generating meaning in life, experiencing a dynamic personal relationship with time, redressing inequality while managing added challenges/vulnerability, and directing life from resilience to flourishing. The five group-specific sub-themes developed illuminate differences in the meaning ascribed to personal recovery by each group. CONCLUSION: Findings emphasise the role of time in how personal recovery is conceptualised by service users and identify ways clinical recovery may influence personal recovery meaning in FEP at mid-later life. Mental health services failing to consider temporal changes in meaning-making and discounting clinical recovery risk ignoring key factors affecting personal recovery.

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.