Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis ...with those psychiatric disorders. The present study sought to use existing summary‐level data from previous genome‐wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune‐related phenotypes. We estimated heritability and examined pair‐wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune‐related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit‐hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome‐wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune‐related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.
Purpose
Exposure to prenatal stress has been reported to affect the risk of adverse neurodevelopmental outcomes in the offspring; however, there is currently no clear consensus. The aim of this ...systematic review and meta-analysis was to examine the existing literature on the association between prenatal stress and autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) in the offspring.
Methods
Based on a registered protocol, we searched several electronic databases for articles in accordance with a detailed search strategy. We performed this study following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
Results
Prenatal stress was significantly associated with an increased risk of both ASD (pooled OR 1.64 95% CI 1.15–2.34;
I
2
= 90%; 15 articles) and ADHD (pooled OR 1.72 95% CI 1.27–2.34;
I
2
= 85%; 12 articles).
Conclusions
This study suggests that prenatal stress may be associated with ASD and ADHD; however, several limitations in the reviewed literature should be noted including significant heterogeneity and there is a need for carefully controlled future studies in this area.
Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ...ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.
Background
Children with autism spectrum disorder (ASD) often have co‐occurring symptoms of attention‐deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise ...from shared or distinct developmental pathways. We explored this question by testing the specificity of early‐life (infant and toddler) predictors of mid‐childhood ADHD and anxiety symptoms compared to ASD symptoms.
Methods
Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7 years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early‐life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early‐life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early‐life predictors and mid‐childhood ADHD and anxiety symptoms compared to mid‐childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations.
Results
Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk‐group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk‐group in path analysis, the association between shyness and anxiety became nonsignificant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal.
Conclusions
The specificity of early‐life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early‐life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders.
Attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurobehavioral disorders of childhood and can profoundly affect children's academic achievement, well-being, and social ...interactions. The American Academy of Pediatrics first published clinical recommendations for evaluation and diagnosis of pediatric ADHD in 2000; recommendations for treatment followed in 2001. The guidelines were revised in 2011 and published with an accompanying process of care algorithm (PoCA) providing discrete and manageable steps by which clinicians could fulfill the clinical guideline's recommendations. Since the release of the 2011 guideline, the
has been revised to the fifth edition, and new ADHD-related research has been published. These publications do not support dramatic changes to the previous recommendations. Therefore, only incremental updates have been made in this guideline revision, including the addition of a key action statement related to diagnosis and treatment of comorbid conditions in children and adolescents with ADHD. The accompanying process of care algorithm has also been updated to assist in implementing the guideline recommendations. Throughout the process of revising the guideline and algorithm, numerous systemic barriers were identified that restrict and/or hamper pediatric clinicians' ability to adopt their recommendations. Therefore, the subcommittee created a companion article (available in the Supplemental Information) on systemic barriers to the care of children and adolescents with ADHD, which identifies the major systemic-level barriers and presents recommendations to address those barriers; in this article, we support the recommendations of the clinical practice guideline and accompanying process of care algorithm.
We examined long-term outcomes of attention-deficit/hyperactivity disorder (ADHD) in a population-based sample of childhood ADHD cases and controls, prospectively assessed as adults.
Adults with ...childhood ADHD and non-ADHD controls from the same birth cohort (N = 5718) were invited to participate in a prospective outcome study. Vital status was determined for birth cohort members. Standardized mortality ratios (SMRs) were constructed to compare overall and cause-specific mortality between childhood ADHD cases and controls. Incarceration status was determined for childhood ADHD cases. A standardized neuropsychiatric interview was administered.
Vital status for 367 childhood ADHD cases was determined: 7 (1.9%) were deceased, and 10 (2.7%) were currently incarcerated. The SMR for overall survival of childhood ADHD cases versus controls was 1.88 (95% confidence interval CI, 0.83-4.26; P = .13) and for accidents only was 1.70 (95% CI, 0.49-5.97; P = .41). However, the cause-specific mortality for suicide only was significantly higher among ADHD cases (SMR, 4.83; 95% CI, 1.14-20.46; P = .032). Among the childhood ADHD cases participating in the prospective assessment (N = 232; mean age, 27.0 years), ADHD persisted into adulthood for 29.3% (95% CI, 23.5-35.2). Participating childhood ADHD cases were more likely than controls (N = 335; mean age, 28.6 years) to have ≥1 other psychiatric disorder (56.9% vs 34.9%; odds ratio, 2.6; 95% CI, 1.8-3.8; P < .01).
Childhood ADHD is a chronic health problem, with significant risk for mortality, persistence of ADHD, and long-term morbidity in adulthood.
Overdiagnosis and underdiagnosis of attention-deficit/hyperactivity disorder (ADHD) are widely debated, fueled by variations in prevalence estimates across countries, time, and broadening diagnostic ...criteria. We conducted a meta-analysis to: establish a benchmark pooled prevalence for ADHD; examine whether estimates have increased with publication of different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM); and explore the effect of study features on prevalence.
Medline, PsycINFO, CINAHL, Embase, and Web of Science were searched for studies with point prevalence estimates of ADHD. We included studies of children that used the diagnostic criteria from DSM-III, DSM-III-R and DSM-IV in any language. Data were extracted on sampling procedure, sample characteristics, assessors, measures, and whether full or partial criteria were met.
The 175 eligible studies included 179 ADHD prevalence estimates with an overall pooled estimate of 7.2% (95% confidence interval: 6.7 to 7.8), and no statistically significant difference between DSM editions. In multivariable analyses, prevalence estimates for ADHD were lower when using the revised third edition of the DSM compared with the fourth edition (P = .03) and when studies were conducted in Europe compared with North America (P = .04). Few studies used population sampling with random selection. Most were from single towns or regions, thus limiting generalizability.
Our review provides a benchmark prevalence estimate for ADHD. If population estimates of ADHD diagnoses exceed our estimate, then overdiagnosis may have occurred for some children. If fewer, then underdiagnosis may have occurred.
Background
Attention‐deficit/hyperactivity disorder (ADHD) often emerges during the preschool years and remains impairing throughout the life span. Early identification and intervention may yield ...lasting benefits that alter the often‐adverse trajectory of the disorder.
Methods
This Practitioner Review provides up‐to‐date information regarding the evaluation and treatment of ADHD in preschool children. The clinical presentation of ADHD in preschool children, its persistence into later childhood, the applicability of DSM‐5 criteria for preschoolers with ADHD, and early predictors of long‐term trajectories are addressed, as well as current findings from randomized controlled trials of both nonpharmacological and pharmacological interventions.
Results
Symptoms of hyperactivity/impulsivity extend down to age 3, but several inattention symptoms, as defined by DSM‐V, less accurately differentiate preschoolers with and without ADHD. Most preschool youth with ADHD symptoms continue to manifest symptoms and impairment into school‐age and adolescence. However, few predictors of persistence beyond early severity have been identified. Behavioral interventions constitute a first‐line treatment for preschool ADHD symptoms, with telepsychiatry increasing in prominence to help to mitigate financial, geographic, and/or logistical barriers to care. Pharmacological interventions, particularly psychostimulants, also confer demonstrable benefits, yet efficacy and safety profiles are less desirable relative to findings in school‐age youth.
Conclusions
Acute treatments have demonstrable efficacy, but do not appear to fundamentally alter underlying mechanisms or long‐term trajectories.
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