Compulsivity, GABA and Gender Differences in PWS 

Travis Thompson, Merlin Butler, Kathryn Ellerbeck, Mary  Caruso & Jennifer Zarcone 

Affiliations:  Institute for Child Development, University of Kansas Medical Center, Kansas City, KS and Children's Mercy Hospital, Kansas City, KS 

Two studies are described concerning the relation between GABA and compulsivity and gender differences in the Prader Willi syndrome phenotype. 

Study I:  22 adults with PWS who have deletions (DEL) and 9 adults with maternal disomy (MUPD) were compared with 21 CA, MA and BMI matched controls for possible relation between blood GABA and compulsivity.  Plasma GABA levels were assessed with high pressure liquid chromatography

and found to be significantly higher among people with MUPD than either DEL or matched controls (p < .05).  Individuals with PWS and the lowest GABA levels were more likely to engage in skin picking.  Plasma GABA was negatively correlated with skin picking on the Compulsive Behavior

Checklist (r= -.42, p= .032)  None of the other measures of compulsivity (YBOCs or CBC) were correlated with plasma GABA.  We previously reported that CBC skin picking factored independently from other measures of compulsivity in a factor analytic study of people with PWS.  

Study 2: 22 males and 27 females with PWS, 10-49 years of age were studied for possible gender differences in phenotypic features.  11 of the males had deletions and 10 had UPD.  16 females had deletions and 11 had UPD.   No IQ differences were found by gender.  Though skin picking was significan

tly more common among people with deletions than UPD, there were no gender differences in this variable.  Females with deletions had more skin picking than females with UPD.  Males had significantly higher Yale Brown Obsessive Compulsive Behavior Scores than females, which could not be

accounted for by UPD vs. DEL differences between genders.  The greatest differences were found in Obsessions (p <.01) though compulsions were also higher for males than females (p< .05).   

Discussion:  The relation of abnormalities in GABA-A receptors associated with deletion or inactivation of GABA-A receptor subunit genes on the 15q11q13 region will be discussed.   We recently reported (Holsen and Thompson, 2002)  that an indirect measure of brain dopamine (eye blink rate) is significantly higher among people with PWS than matched controls, and that eye blink rate  is correlated with compulsivity in PWS as well as matched controls.  Sex differences may be related to modulation of

estrogen and progesterone dopamine activity in the stiratum and nucleus accumbens.  Though GABA-A receptor genes have generally not been thought to be imprinted in MUPD, recent reports suggest that the GABA-A beta 3 gene may be imprinted (e.g. Bittel and Butler, 2002) which is consistent with elevated GABA in MUPD as well as DEL.

Travis Thompson, Ph.D.
Smith Professor of Psychiatry
Director, Institute for Child Development
University of Kansas Medical Center
Kansas City, KS 66160-7340
 

July 2002