Brain and behavior in individuals with intersex conditions

Information

  • Research Project
  • 8963733
  • ApplicationId
    8963733
  • Core Project Number
    R01HD081720
  • Full Project Number
    1R01HD081720-01A1
  • Serial Number
    081720
  • FOA Number
    PA-12-111
  • Sub Project Id
  • Project Start Date
    8/14/2015 - 9 years ago
  • Project End Date
    5/31/2020 - 4 years ago
  • Program Officer Name
    FREUND, LISA S
  • Budget Start Date
    8/14/2015 - 9 years ago
  • Budget End Date
    5/31/2016 - 8 years ago
  • Fiscal Year
    2015
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    8/14/2015 - 9 years ago
Organizations

Brain and behavior in individuals with intersex conditions

? DESCRIPTION (provided by applicant): Studies of non-human mammals show that androgens, particularly testosterone (T), during early development play a major role in sexual differentiation of the brain, with long-term consequences for behavior. Research on clinical populations suggests that prenatal T exposure has similar effects in humans, increasing male-typical behavior and reducing female-typical behavior. Almost nothing is known, however, about the impact of early T exposure on the structure of the human brain. In addition, the brain mechanisms underlying T-related behavioral changes are unknown. This project will study brain structure and behavior in individuals with one of two disorders of sex development (DSD, also called intersex conditions) that are characterized by androgen abnormality beginning prenatally: 1. Congenital adrenal hyperplasia (CAH), which causes overproduction of adrenal androgens; and 2. Complete androgen insensitivity syndrome (CAIS), which involves an inability to respond to androgens, and so an effective lack of androgen exposure. CAH affects both males and females, and 35 men and 35 women with CAH will be compared to 35 male and 35 female controls. Individuals with CAIS are XY females, and 35 females with CAIS will be compared to 35 male and 35 female controls. State-of- the-art imaging technology will be used to map brain structure. Also, aspects of behavior, known to show substantial sex differences, and for which there is evidence of a relationship to prenatal T exposure, will be assessed. Specifically, these are mental rotation ability, targeting ability, and propensities to physical aggression (where men score higher than women), and verbal fluency, fine motor ability and empathy (where women score higher than men). The information obtained will provide convergent evidence regarding the influence of T on human brain and behavior. Convergent evidence is important because ethical considerations preclude experimental manipulations of T during early human development. Instead, naturally occurring conditions that involve T excess or deficiency will be studied. Each condition involves consequences in addition to T abnormality. Therefore, confidence that testosterone caused any brain or behavior differences is strengthened when data from both conditions suggest this conclusion. For instance, prior research indicates that, with respect to physical aggression, men score higher than women, and females with CAH score higher than other females. If XY females with CAIS resemble women rather than men in regard to physical aggression, confidence that T is the responsible agent will be increased. The information obtained will enhance understanding of the neural mechanisms involved in sexual differentiation of human brain and behavior, and so will be relevant to the many psychological disorders that differ by sex. It will also be relevant to clinical management of individuals who have experienced T abnormality before birth, for any of several reasons, including genetic disorders, such as CAH or CAIS, or other disorders of sex development, maternal treatment with hormones during pregnancy, or contact with environmental endocrine disruptors.

IC Name
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
  • Activity
    R01
  • Administering IC
    HD
  • Application Type
    1
  • Direct Cost Amount
    346643
  • Indirect Cost Amount
    15614
  • Total Cost
    362257
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    865
  • Ed Inst. Type
  • Funding ICs
    NICHD:362257\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    DBD
  • Study Section Name
    Developmental Brain Disorders Study Section
  • Organization Name
    UNIVERSITY OF CAMBRIDGE
  • Organization Department
  • Organization DUNS
    226552610
  • Organization City
    CAMBRIDGE
  • Organization State
  • Organization Country
    UNITED KINGDOM
  • Organization Zip Code
    CB2 1TN
  • Organization District
    UNITED KINGDOM