novel clinical target in fragile x syndrome

Conditions: Fragile X Syndrome (FXS)

Summary: fragile x syndrome (fxs) is the most common genetic cause of autism spectrum disorder (asd). the investigators wish to examine brain distribution of sigma-1 receptors in young adult males with fxs using 18f-ftc-146 pet. this project will study the distribution of sigma-1 receptors in 15 young (18-30 years) male adults with fxs compared to 5 healthy adult volunteers.

in this study, we measured sigma-1 receptor density in the regions of interest in brain known to be involved in executive functioning and cognition using 18f-ftc-146 pet. we then compared s1r density in areas rois not involved in executive functioning and cognition. this provided a framework for predicting functional impairment based on brain-behavior relationships. the study had two aims. the first aim was to evaluate the reliability of 18f-ftc-146 brain uptake in healthy controls under test and retest conditions to establish a baseline measure of s1r density and quantify regional brain uptake of radiotracer in five healthy adults. the second aim was to characterize s1r density in brains of young adult males with fxs which will then be compared to healthy volunteers. this was the very first pet study to image sigma-1 receptor density in participants with fragile x syndrome, thereby testing whether altered receptor density is present in brain in fragile x syndrome patients when compared to healthy volunteers. if confirmed, the current study would have provided compelling clinical-translational support for an important pathophysiological mechanism of cognition and executive function. the study had considerable potential for advancing the neurobiological understanding of fragile x syndrome in humans.

Eligibility criteria:
inclusion criteria inclusion criteria for healthy volunteers: 1. ages 18-65 2. either gender and all ethno-racial categories 3. capacity to provide informed consent 4. female participants are expected to use an effective method of birth control throughout the study which includes: hormonal methods (birth control pills, patches, injections, vaginal ring or implants), barrier method (condom or diaphragm) used with spermicide, intrauterine device (iud), or abstinence (no sex) 5. can travel to stanford for 2 scan days. inclusion criteria for individuals with fxs: 1. males who are physically healthy 2. aged between 18 and 30 years inclusive 3. can travel to stanford for a 2-day visit. 4. iq between 40 and 80 points. 5. ability to remain seated for more than 10 minutes. 6. have an established genetic diagnosis of fxs (full mutation with evidence of aberrant methylation of the fmr1 gene, confirmed by genetic testing). exclusion criteria exclusion criteria for healthy volunteers: 1. any current or lifetime psychiatric diagnosis 2. current or past use of psychotropic medication for purposes of treating a mental illness 3. pregnant or nursing females 4. major medical or neurological problem, including anemia (hb , 12 g/dl in women and \<14 g/dl in men) (e.g., unstable hypertension, seizure disorder, head trauma) 5. current diagnosis of vasculopathy or raynouds 6. participant is unable to tolerate being off of anticoagulant medication during study 7. positive urine screen for illicit drugs 8. presence of metal in the body that is contraindicated for mri scans 9. current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures does not exceed defined annual limits 10. stanford university student status (i.e., we will exclude students such as undergrads, grad students and postdocs that currently attend at stanford university) exclusion criteria for individuals with fxs: 1. any contraindication for mri scanning procedures (metal in body, braces, claustrophobia, etc.) 2. no history of with substance abuse, traumatic brain injury and 3. bmi greater than 18.5 4. diagnosis of a known genetic disorder (other than fxs). 5. active medical problems such as unstable seizures, congenital heart disease, endocrine disorders. 6. significant sensory impairments such as blindness or deafness. 7. dsm-5 diagnosis of other severe psychiatric disorder such as bipolar disorder or schizophrenia. 8. pre-term birth (\<34 weeks' gestation) or low birth weight (\<2000g). 9. current use of benzodiazepines. individuals who are taking concomitant psychoactive medications will be tracked and examined in post-hoc analyses, given that it is extremely difficult to recruit individuals who are medication-free or who are willing to go off those medications prior to entering the study. 10. current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures does not exceed defined annual limits

Keywords: fxs