This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: We propose to obtain neuropsychological testing and MRI/MRS in community controls and three groups of juvenile offenders. Among the offender groups will be those with Bipolar Disorder (CD-BP), those with Intermittent Explosive Disorder (CD-IED) and offenders with conduct Disorder but no other major mental illness (CD). We hypothesize that: (1) Both dorsolateral and orbitomedial prefrontal cortex volume will be smaller in our CD-BP and CD-IED groups compared to CD and controls; (2) Levels of N-Acetylaspartate (NAA) will be decreased in the frontal and temporal lobes of subjects CD-BP relative to other groups; and (3) The MRI and MRS findings will be associated with underlying neuropsychological deficits. RESEARCH PLAN: We will recruit 20 adolescents - 15 juvenile offenders, five for each diagnostic group, and five community controls. Subjects will be ages 13-17. The juvenile offenders will come from a secure residential treatment center. METHODS: The research will proceed in three steps: 1. Psychiatric Diagnosis and group classification: A board certified Child and Adolescent psychiatrist will perform semi-structured diagnostic interviews to the subjects and their parents. In addition, a research associate will administer a number of validated rating scales on a weekly basis, monitoring the child's mood and behavior over an eight-week period. Based on the history and direct observation, we will form the diagnostic groups. 2. Neuropsychological testing: Subjects who meet criteria for the selected diagnoses will then undergo neuropsychological testing, conducted over two sessions by a licensed pediatric neuropsychologist. Tests will measure IQ, Executive Function, Verbal/Language skills, and Visuo-spatial skills. 3. Neuroimaging section: Subjects will then undergo a brain MRI and MRS. The volume of gray and white matter and CSF in the brain regions of interest (ROIs) will be estimated. A Proton-MRS study will be done to examine the underlying biochemistry of these ROIs. CLINICAL
There is evidence of detectable brain abnormalities in key brain regions involved in mood regulation and aggression. Considering the preliminary data of similar abnormalities in adolescents with severe aggression and bipolar disorder, there is an important need for additional MRI/MRS studies that will attempt to identify early markers of illness pathophysiology. Such markers could possibly be utilized to identify individuals at high risk for developing such conditions, and who could be the focus of targeted interventions.
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