title: Dysfunctional gene splicing as a potential contributor to neuropsychiatric disorders.
abstract: Alternative pre-mRNA splicing is a major mechanism by which the proteomic diversity of eukaryotic genomes is amplified. Much akin to neuropsychiatric disorders themselves, alternative splicing events can be influenced by genetic, developmental, and environmental factors. Here, we review the evidence that abnormalities of splicing may contribute to the liability toward these disorders. First, we introduce the phenomenon of alternative splicing and describe the processes involved in its regulation. We then review the evidence for specific splicing abnormalities in a wide range of neuropsychiatric disorders, including psychotic disorders (schizophrenia), affective disorders (bipolar disorder and major depressive disorder), suicide, substance abuse disorders (cocaine abuse and alcoholism), and neurodevelopmental disorders (autism). Next, we provide a theoretical reworking of the concept of "gene-focused" epidemiologic and neurobiologic investigations. Lastly, we suggest potentially fruitful lines for future research that should illuminate the nature, extent, causes, and consequences of alternative splicing abnormalities in neuropsychiatric disorders.
authors: Psychiatric Genetic Epidemiology & Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York, USA. glatts@upstate.edu
authors: Stephen J
authors: SJ
authors: Glatt
authors: Ori S
authors: OS
authors: Cohen
authors: Stephen V
authors: SV
authors: Faraone
authors: Ming T
authors: MT
authors: Tsuang
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D006801:Humans; D001523:Mental Disorders / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors