Childhood-early adolescence onset and adult onset schizophrenia: Heterogeneity at the dopamine D3 receptor gene

Maziade, Michel; Roy, Marc‐André; Martínez, María; Gauthier, Benoît; Tremblay, Guy; Fournier, Christiane; Bissonnette, Luc; Simard, Carl; Rouillard, Eric; Mérette, Chantal

doi:10.1016/s0920-9964(97)82249-9

Cited by 5 publications

(7 citation statements)

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“…39 A significant excess of homozygosity has been observed in some studies, 39 an association we also reported for adult-onset SZ in com-parison to childhood onset SZ. 40 Our former finding, 40 the proximity between the DRD3 and the D3S1579 loci and the linkage signal observed in the present study suggest the involvement of the DRD3 locus in the etiology of SZ. Using the broad SZ phenotype, we observed a mod score of 2.06 ( = 0.15) at D10S245, which increased to 2.41 ( = 0.10) under genetic heterogeneity.…”

Section: The Chromosomes 3q 10p and 21qsupporting

confidence: 66%

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes

et al. 2001

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We report the first stage of a genome scan of schizophrenia (SZ) and bipolar disorder (BP) covering 18 candidate chromosomal areas. In addition to testing susceptibility loci that are specific to each disorder, we tested the hypothesis that some susceptibility loci might be common to both disorders. A total of 480 individuals from 21 multigenerational pedigrees of Eastern Qué bec were evaluated by means of a consensus best-estimate diagnosis made blind to diagnoses in relatives and were genotyped with 220 microsatellite markers. Two-point and multipoint model-based linkage analyses were performed and mod scores (Z, for max Z max ) are reported. The strongest linkage signals were detected at D18S1145 (in 18q12; Z = 4.03) for BP, and at D6S334 (in 6p 22-24; Z het = 3.47; ␣ = 0.66) for SZ. Three other chromosomal areas (3q, 10p, and 21q) yielded linkage signals. Chromosomes 3p, 4p, 5p, 5q, 6q, 8p, 9q, 11q, 11p, 12q, 13q, 18p and 22q showed no evidence of linkage. The 18q12 results met the Lander and Kruglyak (1995) criterion for a genome-wide significant linkage and suggested that this susceptibility region may be shared by SZ and BP. The 6p finding provided confirmatory evidence of linkage for SZ. Our results suggest that both specific and common susceptibility loci must be searched for SZ and BP. Molecular Psychiatry (2001) 6, 684-693.Keywords: schizophrenia; bipolar disorder; linkage analysis; psychiatric genetics; family studies Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable disorders probably involving several genes and environmental factors. 1-3 Although previous linkage studies have yielded promising results for both disorders 4-6 (see Riley and McGuffin 7 and Pulver 8 for a recent comprehensive review), their results are often conflicting and difficult to interpret. Methodological obstacles to definitive findings include insufficient statistical power, unknown mode of inheritance, populational differences, uncertain phenotype definitions, 3,9 which also complicate the comparison of results across studies. In addition, studies suggested that some susceptibility loci such as 13q32 5,6 and 18p11 5,10 might be common to both disorders. 11,12 As discussed elsewhere, 2,13,14 such common loci are compatible with previous reports of some degree of coaggregation between SZ and mood disorders. 15 In this context, as a first stage of a genome scan for SZ and BP, we prioritized chromosomal areas based on previous linkage or association results before using, in the second stage, evenly spaced (7-10 cM) markers to cover the rest of the genome which is underway. Our criteria to select candidate areas were based on previous findings of a lod score of at least 2 in the case of parametric (model-based) analyses, or a P-value of at least 0.005 in the case of non-parametric (model-free) analyses. Two other regions were investigated as follow-ups of our own preliminary findings suggesting an association between adult onset SZ and the DRD3 locus 14 and of a suggestive linkage between SZ and 11q21-q24. 16 We r...

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Section: The Chromosomes 3q 10p and 21qsupporting

confidence: 66%

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes

et al. 2001

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“…Potentially, molecular genetic methods have an even greater utility for this purpose (Plomin & Rutter, in press;Rutter & Plomin, 1997) but, so far, there have been only rather exploratory approaches in its use to test discriminative validity (e.g. Maziade et al, 1997).…”

Section: Distinctiveness Of Psychiatric Syndromesmentioning

confidence: 99%

Comorbidity: concepts, claims and choices

Rutter

1997

Criminal Behav Ment Health

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“…Other studies found a positive association only in male subjects (Asherson et al 1996) or in patients with a familial history of schizophrenia (Nimgaonkar et al 1993). Likewise, the BalI polymorphism has been associated with the onset of the disease in certain age groups (Durany et al 1996;Maziade et al 1997).…”

Section: Role In Neuropsychiatric Disordersmentioning

confidence: 94%

The D 3 dopamine receptor in cellular and organismal function

Shafer

Levant

1998

Psychopharmacology

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The D3 dopamine receptor is a member of the family of D2-like dopamine receptors. Since the cloning and identification of the D3 receptor in 1990, considerable progress has been made towards understanding the function of this novel site. Although some avenues of investigation have yielded more definitive results than others, studies to date indicate the D3 receptor is localized preferentially in limbic brain areas and affects locomotion and perhaps reinforcement and reward. A subpopulation of the receptors appear to be autoreceptors which modulate dopamine synthesis, release, and neuronal activity. These observations have led to the hypothesis that the D3 receptor may be an appropriate target in the treatment of neuropsychiatric disorders such as schizophrenia and drug addiction. The role of D3 sites in disease, however, remains to be established. Genetic association of D3 receptor polymorphisms with neuropsychiatric disorders have been proposed. Alterations in expression of D3 sites may occur in some diseases. Although the study of this receptor is clearly in the early stages, these findings lay the foundation for future investigation. In this review, dopamine D3 receptor brain localization, cellular signaling mechanisms, and associated behavior will be discussed. The potential role of the D3 site in neuropsychiatric disorders and as a therapeutic target is also addressed.

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Childhood-early adolescence onset and adult onset schizophrenia: Heterogeneity at the dopamine D3 receptor gene

Cited by 5 publications

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A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes

A search for specific and common susceptibility loci for schizophrenia and bipolar disorder: a linkage study in 13 target chromosomes

Comorbidity: concepts, claims and choices

The D 3 dopamine receptor in cellular and organismal function

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