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Neuroimaging Studies of Pediatric Obsessive–Compulsive Disorder: Special Emphasis on Genetics and Biomarkers

  • Frank P. MacMaster
  • David R. Rosenberg

Abstract

Obsessive–Compulsive Disorder (or OCD) is a severe and chronically debilitating disorder that affects over 3 million people in the United States. People with OCD have distressing obsessions and compulsions that cripple their functioning in every day life. Selective serotonin reuptake inhibitors (SSRIs) are the only FDA approved medications for OCD. However, SSRIs are typically only effective in 40–60% of patients, leaving a substantial number still ill. Indeed, as treatment response is defined by a 20–40% reduction in symptoms, many “responders” are still markedly symptomatic. Approximately 2 million people are not sufficiently served by current medication remedies. Hence, advancement in our understanding of the neurobiology of OCD is sorely needed. The emergence of newer, non-invasive neu-roimaging approaches offers great promise in enhancing our understanding of normative brain development and the developmental neurobiologic underpinnings of childhood onset neuropsychiatric disorders. In this chapter, we describe an approach combining comprehensive assessment and treatment with sophisticated neuroimaging studies to elucidate a mechanistic understanding of the pathogenesis and treatment response of pediatric OCD. Our neuroimaging studies have implicated the cortical—striatal—thalamic—corti-cal (CSTC) loop in the pathophysiology of pediatric OCD. This has led to a focus on the neurotransmitter glutamate. Indeed, our work using proton magnetic resonance spectroscopy (1H-MRS) has shown regionally specific alterations of glutamate/glutamine (or Glx) that resolve with effective treatment. This finding has been supported by other neuroimaging and cerebral spinal fluid (CSF) studies. Genetic studies have noted increased susceptibility to OCD in those expressing alterations in the neuronal glutamate transporter gene (SLC1A1) and certain glutamate receptor genes (GRIK2 and GRIN2B). Additionally, a transgenic animal model of OCD has also noted a high level of glutamatergic excitation as well. Hence, 1H-MRS, CSF, genetic and animal studies have all implicated glutamate in OCD. This has led to the application of the glutamate modulating agents, such as riluzole, to treat OCD symptoms. The approach of bringing neuroimaging and genetic methods to bear on the study of the disorder serves as a model for increasing our understanding of other neuropsychiatric illness.

Keywords

Anterior cingulate glutamate prefrontal cortex obsessive-compulsive disorder striatum thalamus 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Frank P. MacMaster
    • 1
  • David R. Rosenberg
    • 1
  1. 1.Psychiatry & Behavioral NeurosciencesWayne State University School of Medicine, Child Psychiatry and Psychology, Children's Hospital of MichiganUSA

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