Diseases associated with expression schizophrenia

By contrast, studies of the dopamine D -like receptors have found evidence for the association of the receptor with disease (66) these studies have been replicated (41,42). From among the multitude of these studies, only selected examples are reviewed here. For example, evidence both for and against the association of the dopamine D -like receptors with schizophrenia has been reported. Polymorphisms of the dopamine receptor, including the third intracellular loop VNTR, alter dopamine receptor expression. In addition to association with schizophrenia (3,67-70), the dopamine polymorphisms have been associated with the genetic basis of the variable efficacy of antipsychotics such as clozapine (or neuromuscular toxicity—tardive dyskinesia) (69,71,72). Similarly, promoter SNPs have been associated with altered clozapine efficacy (67,68,73). 

Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, et al. 2006. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5 SNPs associated with the disease. Proc Natl Acad Sci USA 103 6747-6752. 

Although there obviously is individual variability in the expression of brain nAChRs in the population, altered expression of some nAChRs relative to healthy controls is associated with several neuropsychiatric disorders. The best-studied example of low nAChR expression in brain and disease is schizophrenia. A second example discussed is autism. 

In contrast to these data on the dopamine D2, the contribution of dopamine D4 polymorphisms to disease is less well understood— although increased levels of dopamine D4 receptor expression in schizophrenia appear to be reproducible in independent studies [71, 72] and may be associated with a Vall94Gly polymorphism [68, 69]. Disorders such as attention-deficit/hyperactivity disorder (ADHD) [74-77] and novelty-seeking behavior [78-80] have also been associated with the D4 dopamine receptor, albeit not consistently [74-80]. 

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