Co-existing psychiatric problems in ADHD in the ADORE cohort

Abstract : Objective : To study the impact of co-existing psychiatric problems with ADHD on behavioural features, psychosocial functioning and quality of life in subjects of the ADORE cohort (N=1,478). Methods : The following six groups of associated psychiatric problems with ADHD were compared: oppositional-defiant disorder or conduct disorder only (ODD/CD); anxiety or depressive disorder only (ANX/DEP); tic/Tourette's disorder only (TIC/ Tourette's); developmental co-ordination disorder only (DCD); two or more associated conditions; and none. Dependent variables included the ADHD Rating Scale-IV, the Strengths and Difficulties Questionnaire, the Clinical Global Impression-Severity scale, the Children's Global Assessment Scale and the Child Health Illness Profile-Child Edition. Results : Having multiple co-existing psychiatric problems increased the severity of ADHD in all domains, be it behavioural features, psychosocial impairment or deterioration of quality of life. A similar though less consistent pattern applied to subjects with co-existing ODD/CD. Conclusions : The ADORE study provides impressive evidence for the far-reaching consequences of co-existing psychiatric problems in children with ADHD that warrant intensive consideration in clinical assessment and treatmen

Efficacy of a skin care cream with TRPV1 inhibitor 4‐t‐butylcyclohexanol in the topical therapy of perioral dermatitis

Background Perioral dermatitis is a clinically distinctive reaction pattern of facial dermatitis, including redness, dryness, burning, pruritus and skin tightness. A gold standard treatment remains unclear. Objectives Our study evaluates the clinical value of a skin care cream with the transient receptor potential vanilloid type 1 inhibitor 4‐t‐butylcyclohexanol in POD patients over 8 weeks. Methods This open, unblinded 8‐week clinical trial included 48 patients. A skin care cream containing 4‐t‐butylcyclohexanol was applied over a period of 8 weeks. Standardized questionnaires were used at baseline, 4 and 8 weeks, for history documentation, objective and subjective severity scores, and quality of life assessments. Six different skin physiology parameters were assessed at all timepoints. Results The perioral dermatitis severity score decreased significantly during the treatment period. This was mirrored by significantly lower patients’ subjective numerical rating score and an improved quality of life score. Transepidermal water loss, stratum corneum hydration and skin erythema improved significantly during the treatment period. Conclusion This transient receptor potential vanilloid type 1 inhibitor‐based skin care cream improved subjective and objective parameters of perioral dermatitis. Decreased transepidermal water loss values and increased stratum corneum hydration demonstrate a restored skin barrier function. Consequently, the topical inhibition of these receptors is a promising management option for POD

Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects

ABSTRACT Background Reaction time (RT) variability is one of the strongest findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). We set out to confirm the association between ADHD and slow and variable RTs and investigate the degree to which RT performance improves under fast event rate and incentives. Using a group familial correlation approach, we tested the hypothesis that there are shared familial effects on RT performance and ADHD. Method A total of 144 ADHD combined-type probands, 125 siblings of the ADHD probands and 60 control participants, ages 6-18, performed a four-choice RT task with baseline and fast-incentive conditions. Results ADHD was associated with slow and variable RTs, and with greater improvement in speed and RT variability from baseline to fast-incentive condition. RT performance showed shared familial influences with ADHD. Under the assumption that the familial effects represent genetic influences, the proportion of the phenotypic correlation due to shared familial influences was estimated as 60-70%. Conclusions The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADH

Confirmation that a specific haplotype of the dopamine transporter gene is associated with Combined-Type ADHD

Objective: The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source of the heterogeneity seen across published studies. Method: The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands. Results: The original observations were confirmed, with an overall odds ratio of 1.4 across samples. Conclusions: These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required. <br/

Missed injuries in trauma patients: A literature review

<p>Abstract</p> <p>Background</p> <p>Overlooked injuries and delayed diagnoses are still common problems in the treatment of polytrauma patients. Therefore, ongoing documentation describing the incidence rates of missed injuries, clinically significant missed injuries, contributing factors and outcome is necessary to improve the quality of trauma care. This review summarizes the available literature on missed injuries, focusing on overlooked muscoloskeletal injuries.</p> <p>Methods</p> <p>Manuscripts dealing with missed injuries after trauma were reviewed. The following search modules were selected in PubMed: Missed injuries, Delayed diagnoses, Trauma, Musculoskeletal injuires. Three time periods were differentiated: (n = 2, 1980–1990), (n = 6, 1990–2000), and (n = 9, 2000-Present).</p> <p>Results</p> <p>We found a wide spread distribution of missed injuries and delayed diagnoses incidence rates (1.3% to 39%). Approximately 15 to 22.3% of patients with missed injuries had clinically significant missed injuries. Furthermore, we observed a decrease of missed pelvic and hip injuries within the last decade.</p> <p>Conclusion</p> <p>The lack of standardized studies using comparable definitions for missed injuries and clinically significant missed injuries call for further investigations, which are necessary to produce more reliable data. Furthermore, improvements in diagnostic techniques (e.g. the use of multi-slice CT) may lead to a decreased incidence of missed pelvic injuries. Finally, the standardized tertiary trauma survey is vitally important in the detection of clinically significant missed injuries and should be included in trauma care.</p

Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder

Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes.A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence