Pharmacogenomics of Antidepressant Response in Children and Adolescents
Condition: Anxiety Disorders; Depression; Eating Disorders; Obsessive-Compulsive Disorder; Suicide Prevention
MeSH terms: Anxiety Disorders; Suicide; Feeding and Eating Disorders; Obsessive-Compulsive Disorder; Suicide Prevention
Study type: Observational

Summary: 
      This study will identify variations in genes that may be involved in the development of
      suicidal events or certain behaviors in youth who are exposed to antidepressant medications.
    

Detailed description: 
      Pharmacogenomics of Antidepressant Response in Children and Adolescents (PARCA) is a
      sub-study of the Antidepressant Safety in Kids (ASK) study. PARCA and ASK are part of the
      Child and Adolescent Psychiatry Trials Network (CAPTN).

      Selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor
      (SNRI) medications are prescribed to approximately 2 to 3% of American children. Evidence
      suggests that these medications are beneficial for treating obsessive-compulsive disorder
      (OCD), anxiety disorders, and major depressive disorder. Following hearings in February and
      September of 2004, the FDA mandated Black Box warnings for all antidepressants, cautioning
      prescribers about the risk of treatment-emergent suicidal tendency in children and
      adolescents treated with these drugs. Although prescribing waned somewhat following the
      warning, many children continue to receive SSRIs and SNRIs for a variety of conditions that
      do not have empirically validated alternative treatments. Therefore, there is a pressing need
      to clearly understand the safety, tolerability, and effectiveness of SSRIs and SNRIs in
      children and adolescents. This study will identify variations in differentially expressed
      genes that may be involved in the development of suicidal events and certain behaviors in
      youth exposed to antidepressant medications.

      Specific aims of the study include the following:

        1. To establish a genetic susceptibility database by creating a DNA repository of 120
           patients with a prospectively identified "Suicidal Event" and 360 closely matched
           antidepressant-tolerant controls, including rigorous phenotypic characterization of
           these patients;

        2. To establish a genetic susceptibility database by creating a DNA repository of 120
           patients with prospectively identified "Behavioral Activation" and 360 closely matched
           antidepressant-tolerant controls, including rigorous phenotypic characterization of
           these patients;

        3. To establish a genetic susceptibility database by creating a DNA repository of 120
           patients with prospectively identified co-occurring "Suicidal Event and Behavioral
           Activation" and 360 closely matched antidepressant-tolerant controls, including rigorous
           phenotypic characterization of these patients;

        4. To identify genetic polymorphisms responsible for the development of "Suicidal Events"
           using a candidate gene approach, including biosynthetic pathways, metabolizing enzymes,
           transporters, ion channels, and receptors;

        5. To identify genetic polymorphisms responsible for the development of "Behavioral
           Activation" using a candidate gene approach, including biosynthetic pathways,
           metabolizing enzymes, transporters, ion channels, and receptors;

        6. To use these data along with data from the parent study, ASK, to better understand the
           relationship between "Suicidal Events" and "Behavioral Activation."

      Participants will include participants of the ASK study who want to participate in the PARCA
      study. Participants will use a self-collection kit to provide a saliva sample. The saliva
      sample will be mailed to the study center for DNA analysis. There will be no study visits.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Males and Females

        Age 7 -17 years

        Pre-specified disorder of anxiety disorder, depressive disorder, eating disorder, or
        obsessive-compulsive disorder.
      
Biospecimen description: 
      Salivary DNA retained at the Duke Center for Human Genetics
    
Keywords: Suicidal Event; Behavioral Activation