Prevalence and factors associated with parental concerns about development detected by the Parents' Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks in a birth cohort

Objectives: Early identification of developmental vulnerability is vital. This study aimed to estimate the prevalence of moderate or high developmental risk on the Parents' Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks; identify associated risk factors; and examine documentation of the PEDS at well-child checks. Design, participants: A prospective birth cohort of 2025 children with 50% of those approached agreeing to participate. Demographic data were obtained via questionnaires and linked electronic medical records. Telephone interviews were conducted with parents to collect PEDS data. Primary and secondary outcomes: Multiple logistic regression analyses identified risk factors for moderate or high developmental risk on the PEDS. A Cumulative Risk Index examined the impact of multiple risk factors on developmental risk and documentation of the PEDS at the well-child checks. Results: Of the original cohort, 792 (39%) had 6-month, 649 (32%) had 12-month and 565 (28%) had 18-month PEDS data. Parental concerns indicating moderate or high developmental risk on the PEDS were 27% (95% CI 24 to 30) at 6 months, 27% (95% CI 24 to 30) at 12 months and 33% (95% CI 29 to 37) at 18 months. Factors associated with moderate or high developmental risk were perinatal risk (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); maternal Middle Eastern or Asian nationality (OR 6 months: 1.6 (95% CI 1.1 to 2.4)), (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); and household disadvantage (OR 6 months: 1.5 (95% CI 1.0 to 2.2). As the number of risk factors increased the odds increased for high or moderate developmental risk and no documentation of the PEDS at well-child checks. Conclusions: Children with multiple risk factors are more likely to have parental concerns indicating

Effects of polygenic risk for suicide attempt and risky behavior on brain structure in young people with familial risk of bipolar disorder

Bipolar disorder (BD) is associated with a 20–30-fold increased suicide risk compared to the general population. First-degree relatives of BD patients show inflated rates of psychopathology including suicidal behaviors. As reliable biomarkers of suicide attempts (SA) are lacking, we examined associations between suicide-related polygenic risk scores (PRSs)—a quantitative index of genomic risk—and variability in brain structures implicated in SA. Participants (n = 206; aged 12–30 years) were unrelated individuals of European ancestry and comprised three groups: 41 BD cases, 96 BD relatives (“high risk”), and 69 controls. Genotyping employed PsychArray, followed by imputation. Three PRSs were computed using genome-wide association data for SA in BD (SA-in-BD), SA in major depressive disorder (SA-in-MDD) (Mullins et al., 2019, The American Journal of Psychiatry, 176(8), 651–660), and risky behavior (Karlsson Linnér et al., 2019, Nature Genetics, 51(2), 245–257). Structural magnetic resonance imaging processing employed FreeSurfer v5.3.0. General linear models were constructed using 32 regions-of-interest identified from suicide neuroimaging literature, with false-discovery-rate correction. SA-in-MDD and SA-in-BD PRSs negatively predicted parahippocampal thickness, with the latter association modified by group membership. SA-in-BD and Risky Behavior PRSs inversely predicted rostral and caudal anterior cingulate structure, respectively, with the latter effect driven by the “high risk” group. SA-in-MDD and SA-in-BD PRSs positively predicted cuneus structure, irrespective of group. This study demonstrated associations between PRSs for suicide-related phenotypes and structural variability in brain regions implicated in SA. Future exploration of extended PRSs, in conjunction with a range of biological, phenotypic, environmental, and experiential data in high risk populations, may inform predictive models for suicidal behaviors.Australian National Health and Medical Research Council (NHMRC); Lansdowne Foundation, Paul and Jenny Reid, Good Talk, and the Keith Pettigrew Family Bequest. DNA extraction was undertaken by Genetic Repositories Australia (GRA; www.neura.edu.au/GRA), Claudio Toma is a recipient of a “Ramón y Cajal” fellowship (RYC2018-024106-I) from the Spanish MINECO. This research was undertaken with the assistance of resources from the National Computational Infrastructure (NCI), which is supported by the Australian Governmen

Predictors of developmental surveillance completion at six months of age in south western Sydney

Background: While developmental surveillance programs promote early identification of child developmental problems, evidence has indicated suboptimal uptake. This study aimed to identify predictors of developmental surveillance completion at 6 months postpartum. Methods: Questionnaires were administered to the parents of 510 infants who were born in south western Sydney, Australia over a 22-month period. Attendance for developmental screening and completion of the Parents' Evaluation of Developmental Status (PEDS) at 6 months postpartum were modelled separately using multivariable logistic regression. Results: Developmental surveillance attendance was predicted by higher levels of maternal education, annual income and being informed about checks. PEDS completion at 6 months of age was predicted by higher income and being informed, as well as being married, employed, speaking English at home, full-term birth and the professional status of the practitioner completing the check. Conclusions: Barriers to developmental surveillance included low socioeconomic status, linguistic diversity and possible gaps in parental knowledge and professional education. Developmental surveillance rates may be increased by the addition of targeted parental and professional support within current universal frameworks

YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.

Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder. Cases with YWHAE variants were collected through international data sharing networks. To address the specific impact of YWHAE loss of function, we phenotyped a mouse knockout of Ywhae. We report a series of 10 individuals with heterozygous loss-of-function YWHAE variants (3 single-nucleotide variants and 7 deletions <1 Mb encompassing YWHAE but not PAFAH1B1), including 8 new cases and 2 follow-ups, added with 5 cases (copy number variants) from literature review. Although, until now, only 1 intragenic deletion has been described in YWHAE, we report 4 new variants specifically in YWHAE (3 splice variants and 1 intragenic deletion). The most frequent manifestations are developmental delay, delayed speech, seizures, and brain malformations, including corpus callosum hypoplasia, delayed myelination, and ventricular dilatation. Individuals with variants affecting YWHAE alone have milder features than those with larger deletions. Neuroanatomical studies in Ywhae <sup>-/-</sup> mice revealed brain structural defects, including thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus paralleling those seen in humans. This study further demonstrates that YWHAE loss-of-function variants cause a neurodevelopmental disease with brain abnormalities

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness

Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = −0.42, p = 3 × 10−5), with weak evidence of IQ reductions among BD-FDRs (d = −0.23, p =.045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment

Can rights stop the wrongs? Exploring the connections between framings of sex workers’ rights and sexual and reproductive health

<p>Abstract</p> <p>Background</p> <p>There is growing interest in the ways in which legal and human rights issues related to sex work affect sex workers’ vulnerability to HIV and abuses including human trafficking and sexual exploitation. International agencies, such as UNAIDS, have called for decriminalisation of sex work because the delivery of sexual and reproductive health services is affected by criminalisation and social exclusion as experienced by sex workers. The paper reflects on the connections in various actors’ framings between sex workers sexual and reproductive health and rights (SRHR) and the ways that international law is interpreted in policing and regulatory practices.</p> <p>Methods</p> <p>The literature review that informs this paper was carried out by the authors in the course of their work within the Paulo Longo Research Initiative. The review covered academic and grey literature such as resources generated by sex worker rights activists, UN policy positions and print and online media. The argument in this paper has been developed reflectively through long term involvement with key actors in the field of sex workers’ rights.</p> <p>Results</p> <p>International legislation characterises sex work in various ways which do not always accord with moves toward decriminalisation. Law, policy and regulation at national level and law enforcement vary between settings. The demands of sex worker rights activists do relate to sexual and reproductive health but they place greater emphasis on efforts to remove the structural barriers that limit sex workers’ ability to participate in society on an equal footing with other citizens.</p> <p>Discussion and conclusion</p> <p>There is a tension between those who wish to uphold the rights of sex workers in order to reduce vulnerability to ill-health and those who insist that sex work is itself a violation of rights. This is reflected in contemporary narratives about sex workers’ rights and the ways in which different actors interpret human rights law. The creation of regulatory frameworks around sex work that support health, safety and freedom from abuse requires a better understanding of the broad scope of laws, policies and enforcement practices in different cultural contexts and economic settings, alongside reviews of UN policies and human rights conventions.</p

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging