Youth with chronic medical conditions (CMCs) have been reported to be at increased risk for developing anxiety disorders. Importantly, suffering from anxiety may also have an impact on their ...disease-related outcomes. This study set out to systematically review the literature on anxiety and seven CMCs (asthma, congenital heart disease, diabetes, epilepsy, inflammatory bowel disease, juvenile idiopathic arthritis, and sickle cell disease) among youth.
A systematic review was performed according to the PRISMA statement. Searches were conducted across PubMed, PsycNET, Embase, and reference lists of the included studies (1990-2018). Three independent reviewers screened titles and abstracts and conducted full-text assessment. Studies were included if they reported the prevalence of anxiety or the association of anxiety on disease-related outcomes in children and/or adolescents with the focal CMCs.
A total of 53 studies met the predetermined inclusion criteria. Across the CMCs, the prevalence of anxiety disorder was increased in youths with CMCs compared to the general population. Evidence for a relationship between anxiety and adverse disease-related outcomes was limited. For asthma, inflammatory bowel disease, and sickle cell disease, there was some evidence indicating that anxiety was associated with adverse outcomes; supported by two longitudinal studies, one in asthma and one in inflammatory bowel disease. For diabetes, results were inconsistent; with some studies indicating that anxiety was associated with worse and others with better treatment adherence.
The prevalence of anxiety disorders in youth with CMCs is higher than that in the general population. Anxiety may also be associated with adverse disease-related outcomes for youths, but it is not possible to draw definitive conclusions. Longitudinal studies making use of parent/youth composite anxiety measures and a combination of parent/youth reported and objective measures of disease-related outcomes are needed. Given the burden of disease of anxiety disorders, regardless of the impact on the disease outcomes, screening for and treatment of anxiety is recommended in youths with CMCs.
Background
Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated ...specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years.
Methods and scope
We review the methods investigating the polygenic nature of complex disorders. We provide mini‐guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still‐missing heritability.
Findings
Genome‐wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs.
Conclusions
Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors.
Various parental characteristics, including psychiatric disorders and parenting behaviours, are associated with offspring mental health and related outcomes in observational studies. The application ...of genetically informative designs is crucial to disentangle the role of genetic and environmental factors (as well as gene-environment correlation) underlying these observations, as parents provide not only the rearing environment but also transmit 50% of their genes to their offspring. This article first provides an overview of behavioural genetics, matched-pair, and molecular genetics designs that can be applied to investigate parent-offspring associations, whilst modelling or accounting for genetic effects. We then present a systematic literature review of genetically informative studies investigating associations between parental characteristics and offspring mental health and related outcomes, published since 2014. The reviewed studies provide reliable evidence of genetic transmission of depression, criminal behaviour, educational attainment, and substance use. These results highlight that studies that do not use genetically informative designs are likely to misinterpret the mechanisms underlying these parent-offspring associations. After accounting for genetic effects, several parental characteristics, including parental psychiatric traits and parenting behaviours, were associated with offspring internalising problems, externalising problems, educational attainment, substance use, and personality through environmental pathways. Overall, genetically informative designs to study intergenerational transmission prove valuable for the understanding of individual differences in offspring mental health and related outcomes, and mechanisms of transmission within families.
A systematic review of studies using molecular genetics and statistical approaches to investigate the role of common genetic variation in the development, persistence, and comorbidity of childhood ...psychiatric traits was conducted.
A literature review was performed using the PubMed database, following PRISMA guidelines. There were 131 studies meeting inclusion criteria, having investigated at least one type of childhood-onset or childhood-measured psychiatric disorder or trait with the aim of identifying trait-associated common genetic variants, estimating the contribution of single nucleotide polymorphisms (SNPs) to the amount of variance explained (SNP-based heritability), investigating genetic overlap between psychiatric traits, or investigating whether the stability in traits or the association with adult traits is explained by genetic factors.
The first robustly associated genetic variants have started to be identified for childhood psychiatric traits. There were substantial contributions of common genetic variants to many traits, with variation in single nucleotide polymorphism heritability estimates depending on age and raters. Moreover, genetic variants also appeared to explain comorbidity as well as stability across a range of psychiatric traits in childhood and across the life span.
Common genetic variation plays a substantial role in childhood psychiatric traits. Increased sample sizes will lead to increased power to identify genetic variants and to understand genetic architecture, which will ultimately be beneficial to targeted and prevention strategies. This can be achieved by harmonizing phenotype measurements, as is already proposed by large international consortia and by including the collection of genetic material in every study.
There are multiple birth and childhood (twin) cohorts with similar data that, like TEDS and NTR, also include older ages. ...many of those also have genetic data available providing the opportunity ...to add polygenic risk scores to the analyses (Middeldorp et al., ). ...as suggested by Allegrini et al., including polygenic risk scores to a model including family data allows for testing of direct and indirect genetic effects. ...the results of Allegrini et al. suggest that intervening in an early stage of a mental disorder and taking a family based approach could aid in preventing the development of additional problems either in the individual or in their family members.
Identifying young people who are at risk of self-harm or suicidal ideation (SHoSI) is a priority for mental health clinicians. We explore the utility of routinely collected data in developing a tool ...to aid early identification of those at risk.
We used electronic health records of 4610 young people aged 5-19 years who were treated by Child and Youth Mental Health Services (CYMHS) in greater Brisbane, Australia. Two Lasso models were trained to predict the risk of future SHoSI in young people currently rated SHoSI; and those who were not.
For currently non-SHoSI children, an Area Under the Receiver Operating Characteristics (AUC) of 0.78 was achieved. Those with the highest risk were 4.97 (CI 4.35-5.66) times more likely to be categorized as SHoSI in the future. For current SHoSI children, the AUC was 0.62.
A prediction model with fair overall predictive power for currently non-SHoSI children was generated. Predicting persistence for SHoSI was more difficult. The electronic health records alone were not sufficient to discriminate at acceptable levels and may require adding unstructured data such as clinical notes. To optimally predict SHoSI models need to be tested and validated separately for those young people with varying degrees of risk.
Objective:
To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD).
Methods:
Parents of 213 Australian children (5–17 years) with ADHD ...completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons).
Results:
Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3–0.6), less outdoor time (OR = 0.4; 95% 0.3–0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0–10.4), while television (OR = 4.0; 95% CI 2.5–6.5), social media (OR = 2.4; 95% CI 1.3–4.5), gaming (OR = 2.0; 95% CI 1.3–3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2–2.8), and loneliness (OR = 3.6; 95% CI 2.3–5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time.
Conclusions:
COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.
Both common and rare genetic variants (minor allele frequency >1% and <0.1% respectively) have been implicated in the aetiology of schizophrenia. In this study, we integrate single-cell gene ...expression data with publicly available Genome-Wide Association Study (GWAS) and exome sequenced data in order to investigate in parallel, the enrichment of common and (ultra-)rare variants related to schizophrenia in several functionally relevant gene-sets. Four types of gene-sets were constructed 1) protein-truncating variant (PTV)-intolerant (PI) genes 2) genes expressed in brain cell types and neurons ascertained from mouse and human brain tissue 3) genes defined by synaptic function and location and 4) intersection genes, i.e., PI genes that are expressed in the human and mouse brain cell gene-sets. We show that common as well as ultra-rare schizophrenia-associated variants are overrepresented in PI genes, in excitatory neurons from the prefrontal cortex and hippocampus, medium spiny neurons, and genes enriched for synaptic processes. We also observed stronger enrichment in the intersection genes. Our findings suggest that across the allele frequency spectrum, genes and genetic variants likely to be under stringent selection, and those expressed in particular brain cell types, are involved in the same biological pathways influencing the risk for schizophrenia.
Objective:
To determine the financial and non-financial costs of Attention-Deficit/Hyperactivity Disorder (ADHD) across the lifespan.
Method:
The population costs of ADHD in Australia were estimated ...for the financial year 2018 to 2019 using a prevalence approach to cost estimation across all ages. Financial (healthcare, productivity, education and justice systems, and deadweight losses) and non-financial costs were measured (Disability Adjusted Life Years (DALYs)).
Results:
The total social and economic cost of ADHD in 2018 to 2019 were US$12.76 billion (range US$8.40 billion to US$17.44 billion, with per person costs of US$15,664 per year). Productivity costs made up 81% of the total financial costs, followed by deadweight losses (11%), and health system costs (4%). Loss in terms of wellbeing was significant (US$5.31 billion).
Conclusion:
There is a need to raise public awareness of the considerable socioeconomic impact and burden of ADHD in order to drive investment and policy decisions that improve identification and treatment of ADHD.
PDF
