Other areas under investigation for genetic studies include the serotononergic and dopaminergic systems. Van Grootheest et al34 studied a large number of twin pairs at age 12, 14, and 16; only at age 14 and 16 were the prevalence higher in girls; genetic factors contributed at all age groups to obsessive-compulsive symptom liability, with no sex differences. Environmental factors shared by children in the same family contribute to symptom score only at age 12. The same group35 studied mono- and dizygotic twin pairs from 8083 families through parental reports on the Inhibitors,research,lifescience,medical Obsessive Compulsive Scale of the Child Behavior Checklist, and

concluded that obsessive-compulsive Inhibitors,research,lifescience,medical behavior is moderately stable in childhood due to genetic, shared, and nonshared environmental factors. Using the same scale, Hudziack et al36 studied 4246 twin pairs and found genetic factors accounting for 55% of the results, with 45% due to environmental influences. Neuroimaging studies In a review article, MacMaster et al37 reported on the results of an extensive

literature search based on imaging techniques such as functional magnetic resonance (fMRI) and voxel-based morphometry, and concluded that the cortical-striatal-thalamic circuits are the most implicated in pediatric OCD. Glutamatergic signals from the frontal Inhibitors,research,lifescience,medical cortex would stimulate striatal activity, diminishing thalamic inhibition. Results Inhibitors,research,lifescience,medical of this meta-analysis included the following findings in youth with OCD: the cingular gyrus was found to be of greater volume and more active, the striatum is diminished, gray matter density in the orbitofrontal cortex is more elevated and voluminous on the right side, and thalamic volume and corpus callosum

are larger. Inhibitors,research,lifescience,medical Evidence from drug therapy studies indicates a role for the dopaminergic (use of atypical antipsychotics), serotoninergic (use of clomipramine and selective serotonin reuptake inhibitors, SSRIs), and glutamatergic (use of riluzole) systems. Lazaro et al38 report on an fMRI study of 12 children with OCD compared with matched subjects; OCD patients presented significantly higher brain activation bilaterally in the middle frontal gyrus with decreased activation in the left insula and putamen after clinical improvement with 6 months of unless pharmacological treatment. MacMaster et al39 studied 28 treatment-naive pediatric OCD patients compared with 21 BI 6727 in vitro controls using magnetic resonance imaging; OCD patients were found to have a larger right orbitofrontal cortex. PANDAS Karla and Swedo40 examined the role of neuroimmune dysfunction in pediatric OCD. As stated, antibody formation may trigger an inflammatory reaction in the basal ganglia following GABHS, as well as possibly other micro-organisms such as viruses, borrelia, and mycoplasma.