Regulation of Gonadal Steroid and Oxytocin/ Vasopressin Receptors and Effector Systems in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Emory University
Investigators Name
Ciliax, Brian, PhD

The goal of this TSA-sponsored project is to determine whether the amount or distribution of receptors for gonadal steroids (e.g. testosterone and estrogen) and two neuropeptides (oxytocin and vasopressin), as well as the neuropeptides themselves, are altered in postmortem brain tissue from Tourette Syndrome (TS) patients. The study is based on the idea that TS is linked to developmental changes that occur in steroid hormone function. In the brain, two of the major systems controlled by gonadal steroids are those using oxytocin and vasopressin as chemical messengers. These systems in turn control some of the brain regions thought to be responsible for the symptoms of TS (the basal ganglia). Thus, oxytocin and vasopressin cells, which are controlled by gonadal steroids and, in turn, control portions of the basal ganglia, form a pathway within which some defect may skew its normal function and result in TS symptoms. Several findings suggest that gonadal steroids may be linked to the cause of TS. These include: (1) the ratio of males to females with TS is approximately 3:1, (2) the ages when symptoms first appear and progress correspond to the ages when developmental changes in blood levels of androgen (“male”) hormones occur, (3) in preliminary studies, tic severity is correlated with gonadal steroid levels, (4) androgen receptor blockers were an effective treatment in preliminary trials, and (5) differences in the structure of TS brains are thought to be determined by gender. I hypothesize that altered gonadal steroid effector systems (particularly oxytocin and vasopressin cells) in certain brain regions lead to developing TS. (This is based on the general hypothesis of Peterson, et al, Psychoneuroendocrinology, 17(6): 553-63, 1992.) Although preliminary studies point to a defect in gonadal steroid function, the status of gonadal steroid receptors and their control of oxytocin and vasopressin systems in TS brain tissue are unknown. Using tissue from the TSA-supported brain bank, I will test whether there is a difference in gonadal steroid receptor levels in brain regions either containing oxytocin and vasopressin cells or dopaminergic cells of the brainstem. I will also determine whether there are any differences in the amount of oxytocin, vasopressin, and their respective receptors in the same regions as well as in the basal ganglia. This project aims to provide critical information regarding how abnormal regulation of basal ganglia function by gonadal steroids (or their effector systems) could lead to having TS symptoms. Brian J. Ciliax, Ph.D. Emory University School of Medicine Atlanta, GA Award: $40,000 Tourette Association of America Inc. – Research Grant Award 1998