Journal of Psychiatry

Alternative splicing of acid sphingomyelinase in major depression

2^nd International Conference on Psychiatry and Psychiatric Disorders

May 02-04, 2016 Chicago, Illinois, USA

Cosima Rhein

Friedrich-Alexander-University Erlangen-Nuremberg, Germany
The State University of New York at Stony Brook, USA

Posters & Accepted Abstracts: J Psychiatry

Abstract:

A recently developed pathogenic model of major depressive disorder (MDD) involves disturbed neurogenesis in the hippocampus, where the acid sphingomyelinase (ASM)/ceramide system plays an important role and is proposed as a molecular target for antidepressant action. ASM hydrolyzes sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several neuro-psychiatric diseases. We investigated alternative splicing as a novel mechanism for regulating cellular ASM activity in a cell culture model and analyzed the ASM splicing pattern in peripheral blood cells of MDD patients. The ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the cellular ceramide content and exerted a dominant-negative effect on ASM activity in physiological cell models. Alternative splicing of ASM is of functional significance for the cellular stress response and represents a mechanism for maintaining constant levels of cellular ASM enzyme activity. ASM alternative splicing events occurred significantly less frequently in MDD patients compared to healthy subjects. After antidepressant treatment, the frequency of alternatively spliced ASM isoforms changed depending on the type of antidepressant drug. Our research indicates that ASM alternative splicing pattern could be a biological target with diagnostic relevance and could serve as a novel biomarker for MDD.

Biography :

Email: Cosima.Rhein@uk-erlangen.de