Examining Physiology and Brain Function in People With the Fragile X Premutation

FMR1 is a gene associated with fragile X syndrome—the most common cause of mental
retardation—and with social, emotional, and cognitive deficits. The chance of developing
these deficits depends on the number of times the FMR1 gene is repeated on the X chromosome.
Individuals with more than 200 copies of the FMR1 gene have the full fragile X mutation,
putting them at most risk for mental retardation. Individuals with between 55 and 200 copies
of the FMR1 gene have the fragile X premutation; they are much less likely to develop mental
retardation, but they may have subtle social, emotional, and cognitive deficits and their
children are more likely to have the full fragile X mutation. A theory, which this study
will test, holds that the deficits of people with the fragile X premutation are caused by
dysfunction in the limbic system. The limbic system consists of a group of structures in the
brain that govern emotions and behavior. This study will examine people with the fragile X
premutation to determine whether and to what extent they have emotional, social, and memory
deficits. The study will also determine whether changes in fragile X gene function are
related to increased deficits and how the brain, and specifically the limbic system, may be
involved in these deficits.

Participation in this study will last 2 days. Participants will undergo several hours of
testing at a lab on back-to-back days. Testing on the first day will include the following:
providing several saliva samples; undergoing neuropsychological testing, in which
participants will solve different types of problems and be interviewed about their emotional
and social experiences; and undergoing a physical exam and blood draw.

Testing on the second day will include the following: an MRI scan, which will take pictures
of the brain both while participants are resting and while they are performing certain
tasks; more neuropsychological testing similar to that from the day before; and
questionnaires about emotional and social experiences. A family member will also be asked to
fill out a questionnaire about the participant. On 2 other days, participants will be asked
to collect saliva samples while at their homes and send the samples to the study
researchers. In addition, the researchers will keep in contact with participants in case any
follow-up is needed over the next few years.

Inclusion Criteria:

- Possesses FMR1 premutation or is part of the general population control group

- Normal or corrected vision

- Speaks English

Exclusion Criteria:

- Presence of contraindication for brain MRI, such as having metal in the body

- Presence of a major medical condition, such as kidney, heart, or liver disease

- Presence of a neurological disorder

- Current alcohol or drug abuse or dependence

- History of head trauma

- History of brain infection

- Medication affecting cerebral blood flow