Genotype moderates the impact of food additives on hyperactive behavior in children

Introduction: The claim of a relationship between artificial food color and additive (AFCs) intake and behavior is highly contentious. We have shown in a previous population-based trial with 3yo children adverse effects of food additives on parentally-rated hyperactive behaviour (Bateman et al, 2004). The possible role of genetic polymorphisms in moderating this adverse effect has not been previously examined. Methods A randomised, double blind, placebo-controlled, within subject crossover food challenge was used for 144, 8 to 9 year old children and 153, 3 year old children. Following baseline assessment children were placed on a diet eliminating food additives and a benzoate preservative for 6 weeks during which time they were challenged for weekly periods with either a placebo mix or a drink containing sodium benzoate (45mg daily) and one of two mixes of AFCs.: Results: The T939C and Thr105Ile polymorphisms of the histamine N-methyltransferase gene (HNMT) moderated the adverse effect s of AFCs but the polymorphisms in catecholamine genes COMT Val108Met and ADRA2A C1291G did not. These findings point to a possible role for histamine in mediating the effects of food additives and help to explain why there has been inconsistency between previous studies. Conclusions: Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on hyperactivity.<br/

Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood:Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale

Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects)

The feasibility of a strategy for the remote recruitment, consenting and assessment of recent referrals: a protocol for phase 1 of the On-Line Parent Training for the Initial Management of ADHD referrals (OPTIMA)

Background: In the UK, children with high levels of hyperactivity, impulsivity and inattention referred to clinical services with possible attention-deficit/hyperactivity disorder (ADHD) often wait a long time for specialist diagnostic assessment. Parent training (PT) has the potential to support parents during this difficult period, especially regarding the management of challenging and disruptive behaviours that often accompany ADHD. However, traditional face-to-face PT is costly and difficult to organise in a timely way. We have created a low-cost, easily accessible PT programme delivered via a phone app, Structured E-Parenting Support (STEPS), to address this problem. The overall OPTIMA programme will evaluate the efficacy and cost-effectiveness of STEPS as a way of helping parents manage their children behaviour while on the waitlist. To ensure the timely and efficient evaluation of STEPS in OPTIMA, we have worked with children’s health services to implement a remote strategy for recruitment, screening and assessment of recently referred families. Part of this strategy is incorporated into routine clinical practice and part is OPTIMA specific. Here, we present the protocol for Phase 1 of OPTIMA—a study of the feasibility of this remote strategy, as a basis for a large-scale STEPS randomised controlled trial (RCT). Methods: This is a single arm observational feasibility study. Participants will be parents of up to 100 children aged 5-11 years with high levels of hyperactivity/impulsivity, inattention and challenging behaviour who are waiting for assessment in one of five UK child and adolescent mental health or behavioural services. Recruitment, consenting and data collection will occur remotely. The primary outcome will be the rate at which the families, who meet inclusion criteria, agree in principle to take part in a full STEPS RCT. Secondary outcomes include acceptability of remote consenting and online data collection procedures; the feasibility of collecting teacher data remotely within the required timeframe, and technical difficulties with completing online questionnaires. All parents in the study will receive access to STEPS. Discussion: Establishing the feasibility of our remote recruitment, consenting and assessment strategy is a pre-requisite for the full trial of OPTIMA. It can also provide a model for future trials conducted remotely

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

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis

BackgroundFindings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.MethodsWe analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33?332 cases and 27?888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples.FindingsSNPs at four loci surpassed the cutoff for genome-wide significance (p&lt;5×10?8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers.InterpretationOur findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause