الفهرس 
Introduction & Aim of WorkOnly 14 pages are availabe for public view
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Abstract
Historical aspects of the dichotomy between bipolar disorder and schizophrenia raise the question of a continuum between the two entities. Although Kraepelin’s traditional dichotomy is still a common base for clinicians every day: diagnosis, prognosis and treatment, recent genetic and neurobiological data are congruent with a dimensional aspect of schizophrenia and bipolar disorder.
The diagnosis of many psychiatric disorders including schizophrenia and BD relies entirely upon clinical features with no validating biomarkers or diagnostic tests. There is therefore no compelling reason to believe that these diagnostic categories reflect discrete pathophysiological processes.
Rapid advances in molecular genetics provided renewed hopes that specific genetic etiological factors for bipolar disorder and schizophrenia would be found. It was believed that such searches would enable a better understanding of the causal reasons and overlapped area between schizophrenia and bipolar disorder.
Gene mapping studies can potentially be informative in this respect, but linkage and candidate gene association studies have been of limited value; linkage studies typically identify relatively large genomic regions, and candidate gene studies are biased in terms of the genes selected for investigation.
GWAS provide an opportunity for unbiased estimates, but the few replicated risk variants discovered to date explain only a small fraction of the heritability for either schizophrenia or bipolar disorder. Among these variants, there is limited evidence for shared risk. It is clear that many more risk factors remain to be identified. The anticipated availability of denser microarrays on the order of several million common, intermediate, and rare variations will enable much greater coverage in forthcoming GWAS. Indeed, whole genome sequencing will provide the ultimate refinement from this perspective.
One should be mindful that genetic association studies at various degrees of sophistication can only reveal genetic variants that may be “associated” with a given trait or may be “shared in association” by two traits. Establishing them as causal variants or contributing to the etiology need to be pursued using additional techniques such as gene expression studies, animal studies, cellular models, imaging and other behavioral studies. The anticipated small effect sizes detected with these studies should not deter the pursuit of their discovery as small effects may still meaningfully contribute to the risk or the etiology of the diseases in question and have a substantial impact in targeted therapeutics.
The question of shared genetic etiological factors for bipolar disorder and schizophrenia has been investigated extensively in recent years, but comprehensive or unambiguous results remain elusive. There are several lines of evidence that suggest overlap in a small proportion of the etiologic space. Emerging genomic technologies promise more refined examination of this question.