Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients - A generalization of Steen's study on DRD3 and tardive dyskinesia

ArticleinAmerican Journal of Medical Genetics 96(2):187-91 · May 2000with12 Reads
DOI: 10.5167/uzh-94558 · Source: PubMed
Abstract
Neuroleptic induced akathisia is a common and distressful extrapyramidal side effect of antipsychotic treatment. A significant proportion of the variability of its development has been left unexplained and has to be attributed to individual susceptibility. Since hereditary factors have been discussed in the etiology of acute akathisia (AA), part of the individual susceptibility might be of genetic origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug-induced chronic movement disorder, which may be associated with homozygosity for the Ser9Gly variant of the DRD3 gene. Considering expression studies, which demonstrated functional variants of DRD3 polymorphisms, we investigated whether homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA. Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88% incidence of AA as compared with a considerably lower 46.9% incidence of AA in schizophrenic patients nonhomozygous for the 2-2 allele (exact P = 0.0223). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:187-191, 2000.
    • "D2 variants have been associated with movement disorders [18,454647, weight gain [48], and sexual dysfunction [49]. D3 variants have been associated with movement disorders, particularly with TD5051525354. The strongest of these associations showed that a D3 Gly9 variant with high affinity for dopamine was associated with a higher risk of TD and other movement disorders, as shown in a large combined study of 780 patients [50] . "
    Article · Jan 2016
    • "The most severe symptoms occur with maximal binding of basal ganglia DRD2 (Farde, 1992). Individuals vary in their susceptibility for getting symptoms of akathisia, but hereditary factors are likely to confer risk for this disorder (Eichhammer, et al., 2000) and other key adverse events (Barnes et al., 2011). Because DRD2 are involved in the pathophysiology of akathisia, then DRD2 polymorphisms were reasonable candidates for possible genetic risk. "
    Full-text · Dataset · Dec 2012 · Journal of Psychopharmacology
    • "The most severe symptoms occur with maximal binding of basal ganglia DRD2 (Farde, 1992). Individuals vary in their susceptibility for getting symptoms of akathisia, but hereditary factors are likely to confer risk for this disorder (Eichhammer, et al., 2000) and other key adverse events (Barnes et al., 2011). Because DRD2 are involved in the pathophysiology of akathisia, then DRD2 polymorphisms were reasonable candidates for possible genetic risk. "
    [Show abstract] [Hide abstract] ABSTRACT: Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. It is known that extrapyramidal adverse effects are associated with increased drug occupancy of the dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. The aim of this study was to identify whether the A1(T) allele of DRD2/ANKK1 was associated with akathisia (as measured by Barnes Akathisia Rating Scale) in a clinical sample of 234 patients who were treated with antipsychotic drugs. Definite akathisia (a score ≥ 2 in the global clinical assessment of akathisia) was significantly less common in subjects who were prescribed SGAs (16.8%) than those prescribed FGAs (47.6%), p < 0.0001. Overall, 24.1% of A1+ patients (A1A2/A1A1) who were treated with SGAs had akathisia, compared to 10.8% of A1- (thus, A2A2) patients. A1+ patients who were administered SGAs also had higher global clinical assessment of akathisia scores than the A1- subjects (p = 0.01). SGAs maintained their advantage over FGAs regarding akathisia, even in A1+ patients who were treated with SGAs. These results strongly suggested that A1+ variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for akathisia in patients who were treated with SGAs, and these variants may explain inconsistencies found across prior studies, when comparing FGAs and SGAs.
    Full-text · Article · Oct 2012
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