This large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses. ...Using adapted measures from the CRISIS questionnaire, parents of children aged 6–18 (
N
= 1013; 56% male; 62% pre-existing psychiatric diagnosis) and self-reporting children/adolescents aged 10–18 (
N
= 385) indicated changes in mental health across six domains: depression, anxiety, irritability, attention, hyperactivity, and obsessions/compulsions. Changes in anxiety, irritability, and hyperactivity were calculated for children aged 2–5 years using the Strengths and Difficulties Questionnaire. COVID-19 exposure, compliance with emergency measures, COVID-19 economic concerns, and stress from social isolation were measured with the CRISIS questionnaire. Prevalence of change in mental health status was estimated for each domain; multinomial logistic regression was used to determine variables associated with mental health status change in each domain. Depending on the age group, 67–70% of children/adolescents experienced deterioration in at least one mental health domain; however, 19–31% of children/adolescents experienced improvement in at least one domain. Children/adolescents without and with psychiatric diagnoses tended to experience deterioration during the first wave of COVID-19. Rates of deterioration were higher in those with a pre-exiting diagnosis. The rate of deterioration was variable across different age groups and pre-existing psychiatric diagnostic groups: depression 37–56%, anxiety 31–50%, irritability 40–66%, attention 40–56%, hyperactivity 23–56%, obsessions/compulsions 13–30%. Greater stress from social isolation was associated with deterioration in all mental health domains (all ORs 11.12–55.24). The impact of pre-existing psychiatric diagnosis was heterogenous, associated with deterioration in depression, irritability, hyperactivity, obsession/compulsions for some children (ORs 1.96–2.23) but also with improvement in depression, anxiety, and irritability for other children (ORs 2.13–3.12). Economic concerns were associated with improvement in anxiety, attention, and obsessions/compulsions (ORs 3.97–5.57). Children/adolescents with and without pre-existing psychiatric diagnoses reported deterioration. Deterioration was associated with increased stress from social isolation. Enhancing social interactions for children/adolescents will be an important mitigation strategy for current and future COVID-19 waves.
•The prevalence of diagnosed OCD in Canada is 1 in 100 people age 15 and older.•People with OCD are more likely to be diagnosed with other mental health conditions.•People with OCD are more likely to ...be diagnosed with alcohol or substance abuse.•The diagnosis of OCD is associated with adverse childhood experiences.
The objective of this study was to provide epidemiological data regarding obsessive compulsive disorder (OCD) in Canada, and examine related conditions, childhood experiences and healthcare utilization. A Statistics Canada population-based health survey was utilized (N = 25,097). The prevalence of diagnosed OCD in Canada was 0.93% (95% CI 0.75–1.11). People with OCD were younger and more likely to have lower incomes. They were more likely to have mood disorders including depression and bipolar disorder (both diagnosed conditions and by screening), and generalized anxiety disorder. The diagnosis of OCD was also associated with alcohol dependence and substance abuse and dependence. Negative childhood experiences were more common in people with OCD, with 72.33%(95% CI 62.25%–82.41%) of people with OCD having experienced some form of childhood maltreatment. Healthcare utilization was more frequent in people with OCD, but they were also more likely to desire help but feel as if they did not receive it. The higher proportion of people with OCD reporting not receiving the care they needed may reveal a crucial gap in treatment and available resources.
The latest version of the Soil and Water Assessment Tool (SWAT+) features several improvements compared with previous versions of the model, for example, the definition of landscape units that allow ...for a better representation of spatio‐temporal dynamics. To evaluate the new model capabilities in lowland catchments characterized by near‐surface groundwater tables and extensive tile drainage, we assess the performance of two SWAT+ model setups in comparison to a setup based on a previous SWAT model version (SWAT3S with a modified three groundwater storage model) in the Kielstau catchment in Northern Germany. The Kielstau catchment has an area of about 50 km2, is dominated by agricultural land use, and has been thoroughly monitored since 2005. In both SWAT+ setups, the catchment is divided into upland areas and floodplains, but in the first SWAT+ model setup, runoff from the hydrologic response units is summed up at landscape unit level and added directly to the stream. In the second SWAT+ model setup, runoff is routed across the landscape before it reaches the streams. Model results are compared with regard to (i) model performance for stream flow at the outlet of the catchment and (ii) aggregated as well as temporally and spatially distributed water balance components. All three model setups show a very good performance at the catchment outlet. In comparison to a previous version of the SWAT model that produced more groundwater flow, the SWAT+ model produced more tile drainage flow and surface runoff. Results from the new SWAT+ model confirm that the representation of routing processes from uplands to floodplains in the model further improved the representation of hydrological processes. Particularly, the stronger spatial heterogeneity that can be related to characteristics of the landscape, is very promising for a better understanding and model representation of hydrological fluxes in lowland areas. The outcomes of this study are expected to further prove the applicability of SWAT+ and provide useful information for future model development.
The model performance of all three model setups was very good, but the SWAT+ model setup with runoff routing between landscape units performed best. Moreover, the SWAT+ model applications predicted a greater spatial heterogeneity of the water balance components. The representation of hydrological fluxes particularly with regard to groundwater flow, surface runoff, and tile drainage flow differed considerably between the SWAT and SWAT+ model setups.
A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The LG ...allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and LG alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The LA allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
•Review obsessive-compulsive disorder and the role of serotonin system genes.•Summarize candidate serotonin system gene studies conducted and suggest reasons for inconclusive findings.•Help direct ...future genetic studies given our understanding of genetic complexity and phenotypic heterogeneity in OCD.
Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that causes the patient to experience intrusive thoughts and/or to carry out repetitive, ritualized behaviors that are time consuming and impairing. OCD is familial and heritable. The genetic factors responsible for pathogenesis, however, remain largely unknown despite the numerous candidate gene studies conducted. Based on efficacy of serotonin reuptake inhibitors (SRIs) in treating OCD, serotonin system genes have been a dominant focus in OCD candidate gene studies. We review the most commonly studied candidate serotonin system gene variants (specifically in SLC6A4, HTR2A, HTR1B, and HTR2C) and their association with OCD. Although findings to date are mixed, serotonin transporter polymorphism 5-HTTLPR and HTR2A polymorphism rs6311 (or rs6313) are most consistently associated with OCD. Mixed findings may be the result of genetic complexity and phenotypic heterogeneity that future studies should account for. Homogenous patient subgroups reflecting OCD symptom dimensions, OCD subtypes, and sex should be used for gene discovery.
Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder ...GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (r
= 0.49 ± 0.13, p = 9.07 × 10
) and a sizable SNP heritability (SNP h
= 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., r
= 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., r
= -0.25 with body mass index and -0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN-OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.
•The antidepressant knowledgebase in pediatric populations is limited.•Our systematic review of the literature suggests overlaps in the antidepressant pharmacogenetic evidence for pediatric and adult ...populations.•Research to validate current and discover new associations are needed to facilitate use of antidepressant pharmacogeneticsin children.
Antidepressants are frequently prescribed and are the first-line pharmacological treatments for psychiatric disorders in children and adolescents. Although antidepressants are generally effective and well-tolerated by children, between 31% to 48% will not respond and up to 25% will experience an adverse drug reaction. Evidence from adult populations suggests pharmacogenetic information can assist with identifying individuals at greatest risk for poor response or adverse drug reactions but the evidence base in pediatric populations is less clear.
We systematically identified, reviewed, and critically evaluated the antidepressant pharmacogenetics literature among children and adolescents using standardized tools and consensus criteria.
We identified 24 studies, most of which were of fair to moderate quality. Collectively, the studies identified 25 significant gene-antidepressant associations involving 10 genes (ABCB1, BDNF, CYP2C19, CYP2D6, FKBP5, GNB3, HTR1B, HTR2A, SLC6A4, TPH2) and nine antidepressants (amitriptyline, citalopram, escitalopram, fluoxetine, fluvoxamine, nortriptyline, paroxetine, sertraline, and venlafaxine). None of the identified associations have been independently replicated in children.
Included studies were heterogenous in terms of study design, genes and drugs assessed, and outcomes measured.
The antidepressant pharmacogenetics knowledge base in pediatric populations is still emerging, but results to date echo many of the gene-antidepressant associations identified in adult populations. Given ubiquitous prescribing of antidepressants in the care of children and adolescents with psychiatric disorders, further research on identifying new and confirming current gene-antidepressant associations are warranted.
Obsessive–compulsive disorder (OCD) is a common and often debilitating neuropsychiatric condition characterized by persistent intrusive thoughts (obsessions), repetitive ritualistic behaviors ...(compulsions) and excessive anxiety. While the neurobiology and etiology of OCD has not been fully elucidated, there is growing evidence that disrupted neurotransmission of glutamate within corticalstriatal–thalamocortical (CSTC) circuitry plays a role in OCD pathogenesis. This review summarizes the findings from neuroimaging, animal model, candidate gene and treatment studies in the context of glutamate signaling dysfunction in OCD. First, studies using magnetic resonance spectroscopy are reviewed demonstrating altered glutamate concentrations in the caudate and anterior cingulate cortex of patients with OCD. Second, knockout mouse models, particularly the DLGAP3 and Sltrk5 knockout mouse models, display remarkably similar phenotypes of compulsive grooming behavior associated with glutamate signaling dysfunction. Third, candidate gene studies have identified associations between variants in glutamate system genes and OCD, particularly for SLC1A1 which has been shown to be associated with OCD in five independent studies. This converging evidence for a role of glutamate in OCD has led to the development of novel treatment strategies involving glutamatergic compounds, particularly riluzole and memantine. We conclude the review by outlining a glutamate hypothesis for OCD, which we hope will inform further research into etiology and treatment for this severe neuropsychiatric condition.
► Reviews neuroimaging, genetic and animal model studies of OCD. ► Converging evidence suggests post-synaptic dysfunction in glutamate signaling. ► Glutamatergic modulating agents (e.g. riluzole and memantine) have shown efficacy.
Fused silica glass is the preferred material for applications which require long-term chemical and mechanical stability as well as excellent optical properties. The manufacturing of complex hollow ...microstructures within transparent fused silica glass is of particular interest for, among others, the miniaturization of chemical synthesis towards more versatile, configurable and environmentally friendly flow-through chemistry as well as high-quality optical waveguides or capillaries. However, microstructuring of such complex three-dimensional structures in glass has proven evasive due to its high thermal and chemical stability as well as mechanical hardness. Here we present an approach for the generation of hollow microstructures in fused silica glass with high precision and freedom of three-dimensional designs. The process combines the concept of sacrificial template replication with a room-temperature molding process for fused silica glass. The fabricated glass chips are versatile tools for, among other, the advance of miniaturization in chemical synthesis on chip.
PDF
