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.

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.

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.

Identifying high-risk subgroups for self-harm in adolescents and young adults: A longitudinal latent class analysis of risk factors.

BACKGROUND: Self-harm is a major public health concern in young people and is governed by a complex interaction of different risk factors. While many studies have identified these risk factors, less is known about how they tend to co-occur together. METHODS: A latent class analysis was conducted using risk factors for self-harm from two waves at ages 13 and 17 from the Growing Up in Ireland (GUI) study their associations with self-harm were examined longitudinally at ages 17 and 20, respectively. RESULTS: At age 13, there was a 'peer problems' group with higher probabilities of bullying, being unpopular and internalising problems and a 'school and substance use problems' group with higher probabilities of substance use, truancy or excessive absence from school and violence. Both of these two groups had over a two-fold risk of self-harm at age 17 in comparison to the low risk factor group. At age 17, there was a group with depression that was diagnosed by a medical professional with the highest relative risk (RR:13.9 (95 % CI 10.2-19.0)) of self-harm at age 20. Two other groups with undiagnosed depression had high probabilities of being bullied, and either high or low probabilities of substance use that had a 9.4 (95 % CI 6.8-13.1) and 7.4 (95 % CI 5.5-10.0) relative risk of self-harm at age 20, respectively. CONCLUSIONS: Identifying hidden sub-groups using risk factors for self-harm in young people can inform potential public health interventions by clinicians and other professionals who work with young people.

An exploratory study of psychosis risk factors in individuals who are referred but do not meet criteria for an early intervention in psychosis service.

BACKGROUND: The 'at-risk mental state' (ARMS) for psychosis has been critiqued for its limited prognostic ability and identification of a limited proportion of those who will develop a first episode of psychosis (FEP). Broadening the search for high-risk groups is key to improving population-level ascertainment of psychosis risk. AIMS: To explore risk enrichment in diagnostic, demographic and socio-functional domains among individuals referred to an early intervention in psychosis (EIP) service not meeting ARMS or FEP criteria. METHOD: A retrospective file review of 16 years of referrals to a tertiary EIP service in Ireland was undertaken. Diagnostic outcomes from standardised assessments (Structured Clinical Interview for DSM), demographic (age, gender, family history, nationality) and socio-occupational (relationship status, living status, working status) variables were compiled for those not meeting criteria. These were compared with individuals diagnosed with an FEP in the same period. RESULTS: From 2005 to 2021 inclusive, of 2025 index assessments, 27.6% (n = 558) did not meet either FEP or ARMS criteria, which is notably higher than the 5.4% (n = 110) meeting ARMS criteria. This group had high psychiatric morbidity, with 65.4% meeting criteria for at least one DSM Axis I disorder. Depressive, anxiety and substance use disorders predominated. Their functional markers were poor, and comparable to the FEP cohort. CONCLUSIONS: This group is enriched for psychosis risk factors. They are a larger group than those meeting ARMS criteria, a finding that may reflect EIP service configuration. They may be an important focus for further study in the search for at-risk populations beyond the current ARMS model.

Time on our side: An exploratory investigation of the relationship between psychiatric disorder and time attitudes.

Time attitudes indicate how individuals feel about the past, present, and future. A growing body of research has demonstrated that scores on the Adolescent and Adult Time Inventory-Time Attitudes Scale relate meaningfully to a variety of measures of well-being and psychiatric symptomatology. To date, no study has examined how (if at all) Time Attitudes scores relate to psychiatric disorder. The present study used an existing clinical cohort (N = 68) and assessed the associations among time attitudes, lifetime disorder, and a retrospective measure of childhood trauma. Preliminary analyses revealed that mean scores of the six time attitudes in the present study did not differ substantially from scores reported in a recent meta-analysis. Correlations between time attitude scores and retrospective trauma scores were particularly large for past negative and past positive. Individuals with no past or current disorder reported substantially higher positive attitudes and substantially lower negative attitudes than those without a disorder across all three time periods with interpretable effect sizes. Finally, past negative time attitudes scores were significantly associated with lifetime mood or anxiety disorder, prior to adjustment for scores on self-reported childhood trauma. These results suggest that time attitudes could be a variable of consequence beyond feelings of general well-being and beyond psychiatric symptoms. More studies with larger sample sizes are required in order to examine the relationship between time attitudes and psychiatric disorder.

Risk and protective factors for self-harm in adolescents and young adults: An umbrella review of systematic reviews.

We conducted an umbrella review to synthesise the evidence from systematic reviews and meta-analyses that examined the risk and protective factors for self-harm in young people. We searched six different databases and used the AMSTAR-2 checklist for quality assessment. The importance of each risk and protective factor was determined based on (1) the number of times it was identified by general reviews examining any risk or protective factor, and (2) the effect sizes from meta-analyses. There were 61 systematic reviews included in this review. The most frequently identified risk factors for self-harm in young people included childhood abuse, depression/anxiety, bullying, trauma, psychiatric illnesses, substance use/abuse, parental divorce, poor family relationships, lack of friends, and exposure to self-harm behaviour in others. The risk factors with the strongest evidence for an association with self-harm were behavioural disorders, personality disorders and depression or anxiety. There was a dearth of systematic reviews examining protective factors but good family/friend relationships were most frequently identified. There was also evidence to show that non-suicidal and suicidal self-harm shared many of the same risk factors. Clinicians and other professionals who work with young people should be particularly cognisant of the psychiatric and adverse life event risk factors as well as the substance use, education-related and individual-level (e.g. being LGB) risk factors for self-harm. Knowledge of risk factors for self-harm can potentially be used to inform the design and implementation of prevention measures and further research is needed on the protective factors for self-harm.

Pharmacy student attitudes to mental illness and the provision of mental health care: a repeated cross-sectional survey.

BACKGROUND: Attitudes to mental illness are an important factor in the willingness of professionals to engage in mental health care. AIM: The aim of this study was to understand attitudes of undergraduate pharmacy students in Ireland to severe mental illness and the provision of medicines optimisation services as well as the variation in these attitudes throughout the undergraduate course. METHOD: A survey instrument was compiled using existing published research and validated questionnaires. The survey was distributed to students in their first, third and Master of Pharmacy years annually between 2014 and 2019. Although designed as a longitudinal study, following the matching process there were a limited number of students who completed more than one survey and therefore data were treated as independent samples. RESULTS: The overall average response rate was 25% per survey (n = 191 participants) Notwithstanding generally positive attitudes, a sizeable proportion of students felt people with severe depression and schizophrenia were hard to talk to (n = 48, 25.3%; n = 54, 29.2%) Less than half of MPharm students expressed confidence and competence in caring for people with more severe mental illnesses such as bipolar disorder and schizophrenia and 29% (n = 60) of students would feel awkward asking someone about their antipsychotic medication. Almost two thirds (n = 120, 63.8%) expressed an interest in a career in mental health. CONCLUSION: Irish pharmacy students have generally positive attitudes towards people with severe mental illness and provision of medicines optimisation services. There is an opportunity to improve pharmacy graduates perceived competence and confidence to provide mental health services.

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.

Outcomes 1 year after a first episode of psychosis in migrants to the Republic of Ireland.

BACKGROUND: Migration is a robust risk factor for developing a psychotic disorder, yet there is a paucity of research on the outcomes of migrants who develop a psychotic disorder. Identifying sub-groups within FEP cohorts who have a poorer outcome, could assist in the development and delivery of more targeted interventions. AIMS: There is a paucity of research on the outcomes of migrants who develop a psychotic disorder. This study aimed to evaluate a broad range of outcomes for those with a FEP who migrated to the Republic of Ireland, including: (i) symptomatic; (ii) functional; (iii) hospitalisation and (iv) engagement with psychosocial services. METHODS: All individuals with a FEP aged 18 to 65 who presented between 01.02.2006 and 01.07.2014 were included. Structured and validated instruments were used to measure positive, negative, depressive symptoms and insight. RESULTS: Of the 573 individuals with a FEP, 22.3% were first-generation migrants and 63.4% (n = 363) were followed up at 1 year. At this time, 72.4% of migrants were in remission of positive psychotic symptoms compared to 78.5% of the Irish born (OR = 0.84, 95% CI [0.50-1.41], p = .51). In relation to negative symptoms, 60.5% of migrants were in remission compared to 67.2% of the Irish born (OR = 0.75, 95% CI [0.44-1.27], p = .283). There was no difference in the severity of positive, negative or depressive symptoms between groups and there was a trend for the Irish born to have better insight (p = .056). The functional outcomes were similar across groups. One third of migrants were admitted to hospital compared to 28.7% of the Irish born (OR = 1.24, 95% CI [0.73-2.13], p = .426). Just over half of both groups attended CBT and 46.2% of caregivers for migrants attended the psychoeducation programme, compared to 39.7% for the Irish born (OR = 1.30, 95% CI [0.79-2.16], p = .306). CONCLUSIONS: These findings demonstrate that migrants have broadly similar outcomes to the native-born populations, however there is still considerable scope for the outcomes for all individuals affected by psychotic disorders to be improved.

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.

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.

Through COVID-19 and beyond: developing a multidisciplinary telehealth family intervention in first episode psychosis.

The COVID-19 pandemic presents unique challenges to high quality, safe Early Intervention in Psychosis (EIP) service provision. Due to the necessity to ensure EIP continues despite this, we developed a multidisciplinary, blended, telehealth intervention, incorporating psychoeducation and peer support, for family members of first episode psychosis service users: PERCEPTION. This perspective article aims to: describe PERCEPTION; offer reflections on our experience of delivering it; make recommendations for future research; and synthesise key learning to assist the integration of similar interventions in other EIP services. We provide a descriptive account of PERCEPTION's development and implementation, with reflections from the clinicians involved, on supporting families using this approach. We experienced telehealth as patient-focused, safe, and efficient and believe the intervention's blended nature augmented families' engagement. The approach adopted can assist service providers to attain balance between protecting public health and offering a meaningful, therapeutic intervention to support families in the current epoch.

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.

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.

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.

Post-CSCST fellowships: beyond subspecialization.

The transition from higher training to consultanthood is a crucial point in the medical training pathway. Despite comprehensive higher training programs, studies of new consultants have reported a disparity in their sense of preparation for non-clinical and clinical duties. Post- "Certificate of Satisfactory Completion of Specialist Training" (CSCST) fellowships have traditionally been undertaken as a means to access subspecialty clinical training which is otherwise unavailable in higher training programs. However, fellowships have a role beyond this subspecialization model, particularly in meeting the non-clinical training needs of new CSCST graduates.The design and goals of fellowship posts should be considered in this context, to align them with the reported needs of new consultants. Special consideration should be given to defining roles of independence for the fellow and to the nature of the mentorship relationship, distinguishing these posts from higher specialist training. Well-designed post-CSCST fellowships have an important role in facilitating the successful transition to consultanthood.

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.