The dopamine D3 receptor gene is of potential interest in the physiopathology of affective disorder because of its expression pattern in brain structures controlling various aspects of behaviour, cognition and emotions. Moreover, it encodes for a receptor protein that is a target for psychotropic drugs, which turn out to be efficient in the treatment of this disorder. Two polymorphisms have been described at this locus (the Bal I and the Msp I Restriction Fragment Length Polymorphisms) that are useful in genetic studies. We therefore researched these polymorphisms in 60 patients suffering from bipolar affective disorder who were compared with 60 healthy volunteers. No statistical difference was observed between the whole patient sample versus the controls. However, one subgroup [homozygous for the (2-2) Bal I polymorphism] exhibits a characteristic clinical pattern consisting of: manic monopolar form of bipolar disorder, low age of onset and initiation by an acute delusional episode. A gender distribution difference for the Bal I polymorphism (chi 2 = 6.61, degrees of freedom = 1, P = 0.01) was then noted, the bipolar females being preferentially heterozygous, and the males homozygous. These results could involve the dopamine D3 receptor locus as a minor effect gene in the manic depression condition.
"A possible association between the DRD3 gene and bipolar disorder has been reported in a family-based association study (Parsian et al., 1995), but not in other studies (Elvidge et al., 2001; Kirov et al., 1999; Shaikh et al., 1993; Souery et al., 1996). Chiaroni et al. (2000) proposed the involvement of the DRD3 locus in bipolar disorder with the clinical characteristics of the monopolar form mania, a low age of onset, and initiation by an acute delusional episode. Brain-derived neurotrophic factor (BDNF) is important in the development of dopaminergic neurons (Baquet et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes.
We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.
Logistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P=0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P=0.027 and 0.006, respectively).
We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2012; 39(2):382-7. DOI:10.1016/j.pnpbp.2012.07.015 · 3.69 Impact Factor
"The DRD3 gene is considered another important candidate gene for bipolar disorder, and a possible association between that gene and bipolar disorder has been reported in a family-based association study (Parsian et al. 1995). Chiaroni et al. (2000) hypothesized the involvement of the DRD3 locus in bipolar disorder with the clinical characteristics of monopolar form mania, a low age of onset, and initiation by an acute delusional episode. Still other studies (Shaikh et al. 1993; Souery et al. 1996; Kirov et al. 1999; Elvidge et al. 2001) have reported no association between this polymorphism and bipolar disorder. "
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES. Clarifying the association between bipolar I and bipolar II disorders at the genetic level is essential for improving our understanding of them. In this study, we evaluated the hypothesis that the dopaminergic polymorphisms are risk factors for bipolar disorders. We examined the association between the catechol-O-methyltransferase (COMT) Val158Met and dopamine D3 receptor (DRD3) Ser9Gly polymorphisms and bipolar I and II disorders, as well as possible interactions between these genes. METHODS. Seven hundred and eleven participants were recruited: 205 with bipolar I, 270 with bipolar II, and 236 healthy controls. The genotypes of the COMT Val158Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS. Logistic regression analyses showed a statistically significant main effect for the Met/Met genotype of the COMT Val158Met polymorphism (P=0.032) and a significant interaction effect for the Met/Met genotype of the COMT Val158Met and Ser/Ser genotypes of the DRD3 Ser9Gly polymorphism (P=0.001) predicted bipolar I patients. However, there was no association between the COMT Val158Met or DRD3 Ser9Gly and bipolar II. CONCLUSIONS. We provide initial evidence that the COMT Val158Met and DRD3 Ser9Gly genotypes interact in bipolar I and bipolar II disorders and that bipolar I and bipolar II are genetically distinct.
The World Journal of Biological Psychiatry 08/2011; 12(5):385-91. DOI:10.3109/15622975.2010.505298 · 4.18 Impact Factor
"Several studies have identified distinct biological correlates of mania. These include increased dopamine activity (Kaplan & Sadock, 1998), hyperpolarization in transmembrane potentials (El-Mallakh et al., 1996), and changes in dopamine sub-3 receptor mechanisms (Chiaroni et al., 2000). However, here we focus on the correlates of bipolar depression, as compared to unipolar depression. "
[Show abstract][Hide abstract] ABSTRACT: This is a review of the studies comparing unipolar and bipolar depression, with focus on the course, symptomatology, neurobiology, and psychosocial literatures. These are reviewed with one question in mind: does the evidence support diagnosing bipolar and unipolar depressions as the same disorder or different? The current nomenclature of bipolar and unipolar disorders has resulted in research that compares these disorders as a whole, without considering depression separately from mania within bipolar disorder. Future research should investigate two broad categories of depression and mania as separate disease processes that are highly comorbid.
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