COVID-19, hypercoagulation and what it could mean for patients with psychotic disorders

It has been recently shown that COVID-19 is associated with a clinically significant coagulopathy. Several studies have indicated that elevated markers of fibrin degradation (D-dimers) in hospitalised patients are associated with poorer prognosis (death or ICU admission) (Fogarty et al., 2020, Connors and Levy, 2020). Coagulation test screening is suggested and routine thromboprophylaxis measures (including use of low molecular weight heparin) are recommended, although full anticoagulation is not yet advised in the management of such patients unless otherwise clinically indicated (Connors and Levy, 2020). We wish to draw attention to a potentially enhanced risk of thromboembolic complications in patients with psychotic disorders. </p

Prenatal and perinatal complications in the development of psychosis: canaries in the coalmine

Although first suggested as early as the 1930s, the study of obstetric complications as risk factors for later psychotic disorders came to the fore in the late 1980s, when proponents of the neurodevelopmental aetiological model of schizophrenia cited the association between obstetric adversity and later schizophrenia as an essential building block for this theoretical approach. A meta-analytic review of this literature in 2002 concluded that no specific obstetric complications were associated with schizophrenia– rather a host of prenatal and perinatal risk factors of small effect size (typically with odds ratios [ORs] of less than 2).<br

Youth mental health in the time of COVID-19

Youth mental health is a rapidly developing field with a focus on prevention, early identification, treatment innovation and service development. In this perspective piece, we discuss the effects of COVID-19 on young people's mental health. The psychosocial effects of COVID-19 disproportionately affect young people. Both immediate and longer-term factors through which young people are affected include social isolation, changes to the delivery of therapeutic services and almost complete loss of all structured occupations (school, work and training) within this population group. Longer-term mechanisms include the effects of the predicted recession on young people's mental health. Opportunities within this crisis exist for service providers to scale up telehealth and digital services that may benefit service provision for young people's mental health in the future

Birth weight and childhood psychopathology in the ABCD cohort: association is strongest for attention problems and is moderated by sex

Many studies have shown low birth weight is associated with psychopathology later in life, particularly attention-deficit/hyperactivity disorder (ADHD). The association is well-replicated, independent from a variety of potential familial confounds, and follows a dose–response curve (decreasing birth weight linked with increasing odds of disorder). However, the specificity of the association to attention problems is called into question by the extent of comorbidity in ADHD, and recent findings that the association is stronger for autism than ADHD. We test the relative dose–response strength of birth weight on multiple aspects of behavior to explore specificity of the effect to attention problems. We also test recent suggestions that the association between birth weight and attention problems is driven by males. Our sample consisted of 9,076 children aged 9–10 from the United States (Adolescent Brain Cognitive Development study). Outcomes included 9 problem-scales and the total problems scale from the Child Behavior Checklist (CBCL). Attention problems were the most strongly associated with birth weight after controlling for gestational age, potential familial confounds, and multiple testing, supporting the outcome-specificity of this association. Contrary to recent registry-based findings, an association between birth weight and an autism scale was not observed. Sex moderated the effect of birth weight on total problems, attention problems and aggressive behavior such that these inverse associations were strongly driven by males. Our findings have strong implications for sex-specific prediction and etiological models of childhood psychopathology.</p

Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment

Aim: Over the past several decades, there has been a growing research interest in the role of inflammation in the pathogenesis of schizophrenia. This review aims to summarize evidence in support of this relationship, to discuss biological mechanisms that might explain it, and to explore the translational impact by examining evidence from trials of anti-inflammatory and immunomodulatory agents in the treatment of schizophrenia.Methods: This narrative review of the literature summarizes evidence from observational studies, clinical trials and meta-analyses to evaluate the role of inflammation in the pathogenesis of schizophrenia and to discuss associated implications for treatment.Results: Epidemiological evidence and animal models support a hypothesis of maternal immune activation during pregnancy, which increases the risk of schizophrenia in the offspring. Several biomarker studies have found associations between classical pro-inflammatory cytokines and schizophrenia. The precise biological mechanisms by which inflammatory processes might contribute to the pathogenesis of schizophrenia remain unclear, but likely include the actions of microglia and the complement system. Importantly, several trials provide evidence that certain anti-inflammatory and immunomodulatory agents show beneficial effects in the treatment of schizophrenia. Nevertheless, there is a need for further precision-focused basic science and translational research.Conclusions: Increasing our understanding of the role of inflammation in schizophrenia will enable novel opportunities for therapeutic and preventative interventions that are informed by the underlying pathogenesis of this complex disorder.</p

Mental health of Irish adolescents following the COVID-19 pandemic: results from a population-based cross-sectional survey

Objectives: This study provides data on the prevalence of mental health problems among adolescents in Ireland in 2021, toward the end of the COVID-19 pandemic. The importance of having recent, large-scale, mental health data for adolescents has been heightened by COVID-19, the increased demand for child and adolescent mental health services, and the rapidly changing adolescent environment. Methods: As part of the Planet Youth study, a cross-sectional survey of adolescents (N = 4,404), mostly aged 15-16, was conducted between September and December 2021. Participants were recruited from 40 schools and non-traditional educational centres across 3 regions in Ireland, one predominantly urban (North Dublin) and two predominantly rural (Cavan, Monaghan). A range of mental health outcomes were self-reported: a single-item question on mental health; the Strengths & Difficulties Questionnaire (SDQ); depressive and anxiety symptoms from the Symptom Check List 90; the Adolescent Psychotic-like Symptom Screener; and lifetime self-harm, suicidal ideation, and attempt. Results: Over a quarter of adolescents described their mental health as 'bad' or 'very bad' (29%), and had SDQ total problem scores over 20 (26%). Over a third (39%) reported self-harming, 42% reported suicidal ideation, and 11% reported attempting suicide, in their lifetime. Gender-diverse youth (non-binary, trans, and undisclosed) had higher rates of poor mental health outcomes compared to cis-gendered youth (male/female), and females had higher rates of most mental health outcomes compared to males. Conclusions: Many of these estimates suggest a deterioration from previous epidemiological studies. While our findings do not definitively prove youth mental health has worsened over time, these findings are highly concerning. We propose a close monitoring of mental health in future surveys of this population and encourage initiatives to improve the capacity and quality of youth mental health services.</p

Omega-3 fatty acid in ultra-high-risk psychosis: A systematic review based on functional outcome.

Aim: Among different types of poly unsaturated fatty acids, omega-3 fatty acids (FA) play a substantial role in brain development and functioning. This review was designed to evaluate and synthesize available evidence regarding omega-3 FAs and functional outcome in the ultra-high-risk (UHR) population.Methods: An electronic search in PubMed, EMBASE, PSYCINFO and COCHRANE search engines has been performed for all articles published until January 2019. The studies that have data regarding omega-3 FAs and functional outcome in UHR population were included.Results: Out of 397 nonduplicate citations, 19 articles met selection criteria. These articles were from four different primary studies, namely the Program of Rehabilitation and Therapy (PORT), the North American Prodromal Longitudinal Studies (NAPLS), Vienna High Risk study (VHR) and the NEURAPRO. The data from the NAPLS study found a positive correlation between functional improvement and frequency of dietary intake omega-3 FA. Moreover, among the erythrocyte omega-3 FA only eicosapentaenoic acid (EPA) showed a positive correlation with functional score. The VHR study found long-term improvement in functional outcome in omega-3 group compared to control, whereas such difference was noticed in the NEURAPRO. In the VHR study both omega-3 and omega-6 together predicted the functional improvement at 12 weeks.Conclusions: The number of studies available remains insufficient and more studies with standardized outcome measures in a clinically comparable UHR population would be of more value to understand the clinical benefits of omega-3 FA in the UHR population.</p

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. </p

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. </p

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. </p