The orphan receptor GPR88 controls impulsivity and is a risk factor for Attention-Deficit/Hyperactivity Disorder.

The neural orphan G protein coupled receptor GPR88 is predominant in the striatum and cortex of both rodents and humans, and considered a potential target for brain disorders. Previous studies have shown multiple behavioral phenotypes in Gpr88 knockout mice, and human genetic studies have reported association with psychosis. Here we tested the possibility that GPR88 contributes to Attention Deficit Hyperactivity Disorder (ADHD).

Cumulative exposure to ADHD medication is inversely related to hippocampus subregional volume in children.

Background: Although there is some evidence for a normalization of brain structure following exposure to ADHD medication, literature on the effects of duration and dose of continued use on the brain is scarce. Here, we investigated the association between cumulative exposure to medication (range 1 week to 4.69 years) and cortical structures and subcortical volumes in a clinical sample of children with ADHD taking medication (n = 109).

Sex-dependent complex association of TPH2 with multiple dimensions of ADHD.

Background: Tryptophan hydroxylase 2 (TPH2) is a key enzyme in the biosynthesis of serotonin in the brain. This study aims to investigate the role of a functional variant in TPH2 (rs17110747) in the pathophysiology of ADHD. This variant has been implicated in mood disorders in recent meta-analysis.

Association between COMT methylation and response to treatment in children with ADHD.

Background: COMT had been considered a promising candidate gene in pharmacogenetic studies in ADHD; yet the findings from these studies have been inconsistent. Part of these inconsistencies could be related to epigenetic mechanisms (including DNA methylation). Here we investigated the role of genetic variants of the COMT gene on the methylation levels of CpG sites in the same gene and explored the effect of methylation on methylphenidate (MPH) and placebo (PBO) response in children with ADHD.

Facing the Methodological Challenge in Dissecting the Genetics of ADHD: A Case for Deep Phenotyping and Heterogeneity Reduction.

Objective: The aetiology of ADHD is complex, with genetic and environmental factors both implicated in the disorder. The most recent ADHD genome-wide association study identified 12 loci that showed significant association with the disorder. However, as highlighted by the authors, these loci "only capture a tiny fraction" of the risk for ADHD.

A polymorphism in the glutamate metabotropic receptor 7 is associated with cognitive deficits in the early phases of psychosis.

Schizophrenia is an illness characterized by positive symptoms, negative symptoms, and cognitive impairments. Cognitive impairments occur before the onset of psychosis and could reflect glutamatergic dysregulation. Thus, identifying associations between genetic variations in genes coding for glutamatergic receptors and cognitive impairment in schizophrenia may help in understanding the basis of these deficits and in identifying potential drug targets.

by Epistatic Interaction in Modulating Behaviors in Children with ADHD: A Pharmaco-Dynamic Behavioral Approach.

Objective: Examining the joint effect of two functional variants in two dopamine-related genes ( and ) on ADHD-relevant behaviors under three experimental conditions (EC).

Method: 362 children with ADHD were assessed by parents and teachers during a week of baseline evaluation, followed by 1 week of MPH and placebo, administered in a double-blind crossover design.

Results: Statistically significant 3-way (-by--by-EC; = .

Therapeutic Response to Methylphenidate in ADHD: Role of Child and Observer Gender.

Objective: This study aims to examine the interaction between the gender of the child and the gender of the observers (teachers, parents) on the therapeutic response (TR) noted with methylphenidate (MPH) in children with ADHD.

Method: Children with ADHD participated in a two week double-blind, randomized, cross-over clinical trial with MPH and placebo, and the difference between the week of treatment with MPH and placebo was calculated for each measure to obtain the treatment response (TR) with MPH. The TR for differences based on the gender of child and the observer was examined by using a univariate analysis of covariance (ANCOVA).

Therapeutic response in children with ADHD: role of observers and settings.

Background: This study aims at characterizing the extent of correlation of treatment response (TR) obtained in various observation settings (home, school, clinic) by different observers (parents, teachers, clinicians).

Methods: Children with attention deficit hyperactivity disorder (ADHD) underwent a 2-week double-blind, randomized, cross-over clinical trial with methylphenidate and placebo, and various measures were obtained during the 2 weeks. Interrelationships of TR were examined using Pearson's correlation coefficients.

Acute blood pressure change with methylphenidate is associated with improvement in attention performance in children with ADHD.

This exploratory study aims to determine whether the change in systolic blood pressure (sBP) after acute methylphenidate (MPH) administration (ΔBP) is associated with the neurocognitive response to MPH in the Conners Continuous Performance Test (CPT) in 513 children with ADHD (aged 6 to 12 years old). We noted that higher increases in sBP were associated with larger improvement in CPT performance with MPH. In the univariate regression model, the ΔBP accounted for an additional 2% of the variance in the change in CPT-Overall Index (OI) after controlling for covariates (p < .

Dissecting genetic cross-talk between ADHD and other neurodevelopmental disorders: Evidence from behavioural, pharmacological and brain imaging investigations.

Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder.

DRD3 Gene and ADHD: A Pharmaco-Behavioural Genetic Study.

Results of candidate gene investigations in ADHD have been difficult to replicate. The complexity of the phenotypes and their underlying determinants, and the relatively small effect sizes of genetic variants may, in part, be contributing to these inconsistencies. The objective of this study is to conduct an exploratory analysis using a comprehensive approach to investigate the role of candidate genes.

exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of treatment response to methylphenidate.

Dopamine plays an important role in modulating attention and motor behaviours, dimensions altered in attention deficit/hyperactivity disorder (ADHD). Numerous association studies have linked dopamine receptor 4 () to increased risk of ADHD. This study investigated the effect of exon 3 polymorphism on child behaviours in response to treatment with methylphenidate.

Placebo response and its determinants in children with ADHD across multiple observers and settings: A randomized clinical trial.

This study aims to quantify placebo response (PR) in children with attention deficit hyperactivity disorder (ADHD) as assessed by parents and teachers and to explore some of its determinants. Five hundred and forty children with ADHD (ages 6-12) were recruited to a randomized, double-blind, placebo-controlled crossover trial with methylphenidate. The main outcome variable was Conners' Global Index (CGI), based on assessment of behaviour by parents (CGI-P) and teacher (CGI-T).

Locus-specific DNA methylation changes and phenotypic variability in children with attention-deficit hyperactivity disorder.

Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD.

Bipolar disorder risk gene modulates negative symptoms in schizophrenia: a neuroimaging genetics study.

Background: Despite being diagnostically associated uniquely with schizophrenia, negative symptoms are also observed in bipolar disorder (BD). Genome-wide association studies (GWAS) have uncovered a number of shared risk genes between schizophrenia and BD. The objectives of this study were to examine whether previously identified risk genes for BD are associated with negative symptom severity within a first-episode schizophrenia (FES) cohort and to examine whether such genes influence brain morphology.

Polygenic Risk Score associated with specific symptom dimensions in first-episode psychosis.

Recent Genome-Wide Association Studies (GWAS) have provided evidence for the involvement of a number of genetic variants in schizophrenia (SCZ). The objective of the current study was to examine the association between these variants and symptom dimensions, evaluated prospectively over a period of 24months, in a clinically well-characterized sample of individuals (n=241) with first-episode psychosis (FEP). The genetic variants were analyzed collectively as captured through a Polygenic Risk Score (PRS), calculated for each individual.

Parental psychopathology in families of children with attention-deficit/hyperactivity disorder and exposed to maternal smoking during pregnancy.

Background: Both genetic and environmental factors have been implicated in the etiology of attention-deficit/hyperactivity disorder (ADHD). We had previously suggested that exposure to maternal smoking during pregnancy (MSDP) may be a valid basis for delineating a distinct subtype of ADHD, where children exposed to MSDP present with a more severe clinical picture. Here, we examine the psychopathology of parents in this group, to better understand the etiology of ADHD.

TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis.

Background: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known.

Aims: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP).

Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis.

Background: The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first-episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation.

Association between obesity-related gene FTO and ADHD.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is an etiologically complex heterogeneous behavioral disorder. Several studies have reported that ADHD subjects are more likely to be overweight/obese and that this comorbidity may be due to shared genetic factors. The objective of this study is to explore the association between ADHD and FTO, a gene strongly associated with obesity in genome-wide studies.

Body weight and ADHD: examining the role of self-regulation.

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD.

Comprehensive phenotype/genotype analyses of the norepinephrine transporter gene (SLC6A2) in ADHD: relation to maternal smoking during pregnancy.

Objective: Despite strong pharmacological evidence implicating the norepinephrine transporter in ADHD, genetic studies have yielded largely insignificant results. We tested the association between 30 tag SNPs within the SLC6A2 gene and ADHD, with stratification based on maternal smoking during pregnancy, an environmental factor strongly associated with ADHD.

Methods: Children (6-12 years old) diagnosed with ADHD according to DSM-IV criteria were comprehensively evaluated with regard to several behavioral and cognitive dimensions of ADHD as well as response to a fixed dose of methylphenidate (MPH) using a double-blind placebo controlled crossover trial.

Family-based association study of ADHD and genes increasing the risk for smoking behaviours.

Objective: To investigate five top single nucleotide polymorphisms (SNPs) located in different genes and loci (CHRNA3, BDNF, DBH and LOC100188947) that were highly associated with different dimensions of smoking behaviour, in relation to attention-deficit hyperactivity disorder (ADHD).

Design: Cohort study consisting of a clinical sample of children with ADHD.

Setting: Douglas Institute ADHD Clinic, Montreal, Canada.