Psychopathology, GABA, and the Rubinstein-Taybi syndrome: a review and case study

Abstract

An adult female with congenital Rubinstein-Taybi syndrome (RTS) and severe mental retardation is described, who presented with symptoms of severe over-activity, short attention span, mood lability, and aggressive outbursts in a cyclical pattern, suggestive of recurrent manic-like episodes. These symptoms improved significantly with divalproex (Depakote) monotherapy. Review of the existing studies showed that 10-76% of persons with RTS may be identified with similar behavioral symptoms. We postulate other persons with RTS may respond to divalproex, and there may be some relationship between the chromosome 16p13.3 deletion and gamma-aminobutyric acid (GABA) receptor or neurotransmitter abnormalities. Recent molecular genetic studies suggest a linkage of this region to bipolar mood disorder and autism, both of which were diagnosed in this patient. Further prospective study is needed of RTS persons regarding behavioral problems, comorbid psychiatric diagnoses, and treatment responses, correlated with genetic abnormalities.