An investigation of psychosis: from the historical background to its neurobiological and genetic underpinnings in different psychiatric disorders

The main aim of this thesis is that of elucidating the genetic basis of psychosis. In order to do that I decided to go back to the historical roots of the disorder, spanning the dichotomy versus continuum argument living on even today, to be able to give a background that explains the current understanding of the disorder. I thus went on to explore the evolution of our understanding by explaining the models that are used today as the most probable explanations, from the models centering around monoamine dysfunction, most notably dopamine dysfunction, to the inflammation and autoimmune hypothesis of psychosis. The discussion then turned to the clinical manifestation of the disorder, its stages, the clinical heterogeneity that makes it so difficult to correctly diagnose and categorize, and the genetic heterogeneity that could be the reason at the roots of this confusion, giving also an overview of the kind of studies and analysis that are used to elucidate the genetic mystery. Through these genetic studies, a number of putative, suggestive genes have been found and well-researched, but I decided to investigate a novel one, that has been found through linkage analysis, on chromosome 22 (exact location 22q12.3). The YWHAH gene is a novel gene with potential for further research as a gene that crosses diagnostic boundaries, that i decided to analyze because of its role in the pathophysiology and etiology of both psychotic bipolar disorder and schizophrenia and its implications in terms of glutamatergic and dopaminergic systems’ involvement.