Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule-related processing, we performed a cue-targe...

Two genome wide scans, one of which was subsequently extended, have led to the identification of different chromosomal regions assumed to harbour genes underlying attention-deficit/hyperactivity disorder (ADHD). Some of these regions were also identified in patients with autism and/or dyslexia. The only region for which both studies detected a LOD score >1 was on chr 5p13 which is in the vicini...

CONTEXT The study and treatment of psychiatric disorders is made difficult by the fact that patients with identical symptoms often differ markedly in their clinical features and presumably in their etiology. A principal aim of genetic research is to provide new information that can resolve such clinical heterogeneity and that can be incorporated into diagnostic practice. OBJECTIVE To test the...

Catechol-O-methyl transferase (COMT) is involved in the inactivation of dopamine in brain regions in which the dopamine transporter (DAT1) is sparsely expressed. The membrane-bound isoform of COMT (MB-COMT) is the predominantly expressed form in the mammalian central nervous system (CNS). It has been a matter of debate whether in neural cells of the CNS the enzymatic domain of MB-COMT is orient...

Cognitive flexibility, the ability to adapt goal-oriented behaviour in response to changing environmental demands, varies widely amongst individuals, yet its underlying neural mechanisms are not fully understood. Neuropharmacological and human clinical studies have suggested a critical role for striatal dopaminergic function mediated by the dopamine transporter (DAT). The present study aimed at...

Genetic associations for Attention Deficit Hyperactivity Disorder (ADHD), a common highly heritable childhood behavioural disorder, require replication in order to establish whether they are true positive findings. The current study aims to replicate recent association findings from the International Multi-centre ADHD Genetics (IMAGE) project in one of the most studied genes related to ADHD, th...

Genetic influences on dopaminergic neurotransmission have been implicated in attention-deficit hyperactivity disorder (ADHD) and are theorized to impact cognitive functioning via alterations in frontal-striatal circuitry. Neuropsychological functioning has been proposed to account for the potential associations between dopamine candidate genes and ADHD. However, to date, this mediation hypothes...

Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected bec...

PURPOSE Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioral disorder characterized by inattention, poor impulse control, and motor restlessness. Risk factors include familial stressors, anxiety disorders, learning disabilities, abnormal brain development, heritability, and dopamine polymorphisms. Children with an orofacial clefting (OFC) history are at increase...