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. A.
Specific Aims Specific Aim 1: To identify the effects of prenatal MA exposure on CNS structure and metabolism in three year old children.
Specific Aim 2 : To examine the relationship between prenatal MA exposure, CNS structure and metabolism, and two cognitive domains, attention and arousal/self-regulation, assessed at 2 and 3 years of age. (The specific aims have not been modified). B. Studies and Results The PI is undertaking a cross-sectional neuroimaging study of three year-old children currently enrolled in the Hawai`i Infant Development, Environment and Lifestyle (IDEAL) study (RO1 DA 014948; Lester, PI). Prospectively collected data will include information about gestational MA and other drug exposure obtained at birth and one month of age, developmental, behavioral, and neuropsychologic measures obtained at 24 months and 36 months, and structural (3 Tesla MRI) and biochemical (1H MRS) neuroimaging data obtained at 36 months. For the neuroimaging studies, specific brain regions of interest (ROI) have been chosen a priori based upon existing preclinical and clinical studies looking at prenatal MA exposure and neurodevelopment. Other covariates measured as part of the IDEAL study include: (1) prenatal marijuana and tobacco exposure; (2) information related to maternal demographics; (3) information describing ongoing drug use, psychological status, parenting stress, intelligence, abuse potential, household conflict, and self-esteem; and (4) neighborhood characteristics assessed by caretaker-report and block group census data. Children who have a history of prenatal alcohol exposure will be excluded. Three cohorts will be recruited: Cohort 1 - those children exposed prenatally to MA and tobacco; Cohort 2 - children exposed prenatally to tobacco; and Cohort 3 - children exposed prenatally to neither MA nor tobacco. With regard to Specific Aim 1, the following progress to date has occurred: 1) the PI has obtained IRB approvals from both institutions where the study procedures will occur (Hawaii Pacific Health and Queens Medical Center), and a Certificate of Confidentiality has been obtained from the DHHS; 2) the MRI protocols needed for the study have been developed and piloted on two volunteer 3 year-old subjects; 3) the PI and the Study Coordinator identified other researchers at mainland institutions with experience scanning unsedated 3 year-old children, and received hands-on training at Johns Hopkins University to learn operant conditioning behavioral techniques to help preschool-aged children comply with the MRI/MRS procedure (a major criticism of the study design by the NIDA-K Training and Development Subcommittee (along with other review groups) was that 3 year-old children might differ greatly in their ability to comply with holding still for the neuroimaging, and that this ability might vary by MA exposure status - therefore, considerable effort was made to learn techniques to improve the overall compliance of all enrolled children); 4) one IDEAL study 3 year-old subject was successfully scanned; 8 additional IDEAL subjects have been consented and are being scheduled for study procedures; an additional 30 IDEAL subjects are eligible through May 2006, but are still pending their 36 month IDEAL study visit, at which time the neuroimaging study will be introduced. Regarding Specific Aim 2, the following progress to date has occurred: 1) considerable time has been spent by the PI developing a working knowledge of Developmental Psychology and Developmental Psychopathology, given that his background as a general pediatrician has provided little background knowledge of these subjects. This training has involved extensive reading of textbooks and peer-reviewed articles, mentor meetings with Dr. Barry Lester (the designated mentor for this topical area), conference attendence, and presentations of the PI s progress at JABSOM research forums; 2) the PI identified a mainland consultant with expertise in executive function testing of preschool-aged children. This consultant visitied UH on April 18th, 2006, and has provided ongoing consultation with the PI. Together with this person, the PI has developed a new battery of neuropsychological measures for Specific Aim 2. Given the preliminary stage of implementation of the research study described above, no results are available for this progress report. C. Significance Multiple questions remain unanswered about how extent and timing of MA exposure and co-exposure to prenatal tobacco and marijuana impact these neurobiological alterations, and whether these alterations ultimately relate to disorders in child behavior. Studies that elucidate the relationships between prenatal drug exposure, neurobiological development and human behavior are critical to support the development of strategies that provide optimal care to at-risk children, and have been identified as a priority area for NIDA. The proposed study will examine the interplay between gestational MA exposure, brain morphology (structural MRI) and chemistry (1H-MRS), and two cognitive domains, attention and arousal/self-regulation. The project is important because it has the potential of advancing our knowledge about how drugs of abuse may impact the developing nervous system. Additionally, the project is important because it applies sophisticated neuroimaging techniques to the study of the largest prospectively followed cohort of children exposed to MA, an increasing important problem facing many communities in the U.S. D. Plans There are no anticipated changes regarding the involvement of Human Subjects or the use of Vertebrate Animals. The major goal of the upcoming year will be the enrollment of subjects and the successful implementation of the research protocol described above. The PI also plans to develop a pilot research proposal examining polymorphisms in dopamine and serotonin genes, in order to begin to assess the relationship of these genetic markers with the neurodevelopment of MA exposed children.
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