Gender Dfferences in Dopamine Receptors Implications for Tourette Syndrome

Grant Type
Clinical
Grant Year
1997
Institution Location
MA
Institution Organization Name
Harvard Medical School
Investigators Name
Anderson, Susan, PhD

Our preclinical observations offer an interesting hypothesis to explain gender differences in Tourette Syndrome (TS) and may be important for understanding why the disorder waxes and wanes during development. Changes in D2 receptor density during development parallel the appearance of TS symptoms and thus may explain the 3-4 fold increased prevalence in males versus females. We have found that Martin Teicher striatal dopamine D2 receptors in male rats rose from childhood to puberty, where they reach their zenith, and then those receptors decline during young adult-hood. However, female rats fail to overproduce dopamine receptors in a similar manner. An analogous finding has been observed in the human male striatum. We hypothesize that these D2 receptors may be a critical, permissive factor that determine the degree and extent to which this genetic disorder is expressed—especially in light of the recent finding of increased D2 receptor density in the more severely affected identical twin with Tourette Syndrome. Also, these observations provide a framework for understanding why certain environmental factors seem to increase the risk that the TS gene(s) will be expressed. These factors include higher levels of gonadal androgens and stress hormones during prenatal development, and exposure to stress, infections, anabolic steroids, cocaine or other stimulants during postnatal development. We postulate that these factors influence the penetrance of the putative TS gene(s) by affecting the normal developmental expression of D2 receptors in the striatum. The aim of these studies is to ascertain how three of the risk factors associated with TS, namely androgens, stimulants and stress affect D2 receptor overproduction and elimination in the striatum. The functional outcome of altered D2 receptor density will also be assessed by probing for the appearance of stereotypic behavior in the treated rats. We hope that data from these projects will make a substantial contribution to the understanding of how environmental factors impact the immature dopamine system and, in turn, how this outcome relates to an underlying vulnerability to the symptoms of TS. Susan L. Andersen, Ph.D. Martin H. Teicher, M.D., Ph.D. Harvard Medical School/McLean Hospital Belmont, MA Award: $33,691 Tourette Association of America Inc. – Research Grant Award 1997