This approach has failed to show real progress in our understanding of the neurobiology of psychiatric illness.19 However, developing an understanding of the physiology of psychiatric disorders has been difficult. That is, until

#www.selleckchem.com/products/PD-0332991.html randurls[1|1|,|CHEM1|]# the development of brain selleck catalog imaging methodologies that have allowed for the in vivo examination of the living brain. Postmortem work, while informative, does have its limits, and samples in pediatric populations with psychiatric illness are rare. There have been 2 decades since the application of brain imaging to the study of OCD, and tremendous progress has Inhibitors,research,lifescience,medical been made. Bringing these advances from the “bench” however, has been difficult. Translational research has in two basic hurdles to jump.20 The first hurdle is in transferring new understandings of the mechanisms of the disorder into novel treatments, diagnostic tools, and prevention. The second hurdle is in taking Inhibitors,research,lifescience,medical these novel therapies, diagnostic and preventative methods, and implementing these protocols in the actual Inhibitors,research,lifescience,medical clinic (Figure 1). As out-lined in the following section, significant progress has been made in increasing our understanding of the neurobiological substrates of pediatric OCD. These advances have directly led to the novel application of agents to treat pediatric OCD. This is one of the rare instances in

psychiatric research where knowledge has indeed moved from the “bench” and closer to the “bedside.” Figure 1. Basic pathway of translational research and the two main hurdles that need to be crossed to make research clinically relevant. The standard method in psychiatry has been to move from pharmacology Inhibitors,research,lifescience,medical in clinical practice to theories of pathophysiology. Basic neurobiological model of pediatric OCD In this section, we will outline the basic neurobiological model of OCD (Figure 2). The cortical-striatalthalamic circuit Inhibitors,research,lifescience,medical has been the most consistently implicated in OCD.21,22 In the striatum, 80% of all synapses are cortical inputs.23 The cortical regions projecting to the striatum can be divided into “motor” and “limbic associative.” Motor

projections include somatosensory, motor, and premotor cortex. More pertinent to OCD, Figure 2. Basic schematic of the cortical-striatal-thalamic-cortical loop pertinent to pediatric obsessive-compulsive disorder. the “limbic associative” projections are derived Drug_discovery from the amygdala, hippocampus, orbital, frontal, cingulate, parietal, temporal, entorhinal, and association cortex.24 One can subdivide the cortical-striatal connections into circuit loops. There are sensorimotor, oculomotor, dorsal cognitive, ventral cognitive, affective/motivational loops that extend from the cortex to the striatum to the thalamus and back to the cortex.22 The anatomy and organization of the cortical-striatal circuits have been reviewed in depth elsewhere.