Systemic and Local Corticosteroid Use Is Associated with Reduced Executive Cognition, and Mood and Anxiety Disorders

Background: Use of local corticosteroids, especially the inhaled types, has increasingly been associated with systemic uptake and consequent adverse effects. In this study, we assessed the associations between the use of different corticosteroid types with cognitive and neuropsychiatric adverse effects related to high glucocorticoid exposure. Methods: In 83,592 adults (mean age 44 years, 59% women) of the general population (Lifelines Cohort Study), we analyzed the relationship between corticosteroid use with executive cognitive functioning (Ruff Figural Fluency Test), and presence of mood and anxiety disorders (Mini-International Neuropsychiatric Interview survey). We performed additional exploration for effects of physical quality of life (QoL; RAND-36), and inflammation (high-sensitive C-reactive protein [CRP]). Results: Cognitive scores were lower among corticosteroid users, in particular of systemic and inhaled types, when compared to nonusers. Users of inhaled types showed lower cognitive scores irrespective of physical QoL, psychiatric disorders, and high-sensitive CRP. Overall corticosteroid use was also associated with higher likelihood for mood and anxiety disorders. Users of inhaled corticosteroids were more likely to have mood disorders (OR 1.40 [95% CI 1.19-1.65], p < 0.001) and anxiety disorders (OR 1.19 [95% CI 1.06-1.33], p = 0.002). These findings were independent of physical QoL. A higher likelihood for mood disorders was also found for systemic users whereas nasal and dermal corticosteroid users were more likely to have anxiety disorders. Conclusions: Commonly used local corticosteroids, in particular inhaled types, and systemic corticosteroids are associated with reduced executive cognitive functioning and a higher likelihood of mood and anxiety disorders in the general adult population

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value &lt; 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel&nbsp;loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations

ein Rückblick auf meine Mitarbeit im Gebiete der Sprach- und Religionswissenschaft

Digitalisat der Ausgabe von 1927, erschienen 201

Anxiety and disruptive behavior mediate pathways from attention-deficit/ hyperactivity disorder to depression

Objective: The progression to depression in children with attention-deficit/hyperactivity disorder (ADHD) is not clearly understood. To clarify this relationship, we tested the following hypotheses in a population-based study: (1) children with ADHD have a higher risk of developing depression than children without ADHD; (2) the pathway from ADHD to depression is mediated (partly) through anxiety and disruptive behavior disorders; and (3) mediation through anxiety is more prevalent in girls, and mediation through disruptive behavior disorders is more prevalent in boys. Method: From October 2008 to September 2010, the Composite International Diagnostic Interview was used to assess ADHD, major depressive episodes, anxiety disorders, and disruptive behavior disorders in 1,584 participants from the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort. Cox regression was used to model the effects of ADHD, anxiety, and disruptive behaviors on depression. Risk of and pathways to depression were studied in both children with ADHD and children with subthreshold ADHD. Results: Comorbid depression was present in 36% of children with a diagnosis of ADHD, 24% of children with subthreshold ADHD, and 14% of children with no ADHD. Anxiety and disruptive behaviors mediated 32% of depression in ADHD. Pathways through anxiety and disruptive behavior disorders were independent of gender. Disruptive behavior disorder was a stronger mediator than anxiety for both genders (all P < .01). Conclusions: These findings may help forewarn of impending depression and therefore allow opportunities for interventions when comorbid anxiety and/or disruptive behavior disorders are present in a child with ADHD

Gene-age interactions in blood pressure regulation: A large-scale investigation with the CHARGE, global BPgen, and ICBP consortia

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p≤ 5 10) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm H

Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper