Missense mutation of the cholecystokinin B receptor gene: Lack of association with panic disorder

Kato, Takeshi; Wang, Zhe Wu; Zoëga, Tómas; Crowe, Raymond R.

doi:10.1002/(sici)1096-8628(19960726)67:4<401::aid-ajmg14>3.3.co;2-u

Cited by 13 publications

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“…Two association studies of a polymorphism in the promoter region of the CCK gene did not find consistent evidence of an association with panic disorder [40,41]. Although no association was seen in a small case-control study of the CCK-B receptor [42], a subsequent study [40] did observe evidence of association in a sample of ethnically matched cases and controls.…”

Section: Molecular Studiesmentioning

confidence: 96%

The genetics of panic disorder

Finn

Smoller

2001

Curr Psychiatry Rep

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Of the anxiety disorders, panic disorder (PD) has been the most extensively studied from a genetic standpoint. Results of family studies have consistently demonstrated that PD runs in families, and twin studies indicate that genes contribute to this familiality. However, phenotypic and genetic complexity has made finding the specific genes involved in PD a challenge. There is still uncertainty about how best to define the phenotype for genetic studies and whether it is the clinical phenotype of PD or more latent psychologic and biologic traits that are inherited. To date, molecular genetic studies have suggested some chromosomal regions and genes that may contribute to risk, but none of these have been established. We review the genetic epidemiology of PD as well as recent molecular genetic studies of the disorder, and conclude with a discussion of promising strategies that attempt to uncover specific genetic loci involved in the etiology of PD.

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Section: Molecular Studiesmentioning

confidence: 96%

The genetics of panic disorder

Finn

Smoller

2001

Curr Psychiatry Rep

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“…A linkage study by Gelernter et al [174] suggested a risk locus at marker CCKBR on chromosome 11p with a LOD score of 2.01. Kato et al [175] were the first to identify a CCKBR missense mutation in exon 2 (1550G/A) and an intron 4 variation (2491C/A) by means of SSCP analysis in patients with PD, which, however, did not show association with the disease in a sample of 34 patients. Another group could confirm non-association of 1550G/A and 2491C/A as well as of two further CCKBR SNPs (1962T/C, 1985G/A) in an independent sample of 91 Japanese patients with PD.…”

Section: Cck-2r Gene (Cckbr; Chromosome 11p154)mentioning

confidence: 99%

Neuronal Network of Panic Disorder: The Role of the Neuropeptide Cholecystokinin

2012

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Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and avoidance behavior. Its pathogenesis is complex and includes both neurobiological and psychological factors. With regard to neurobiological underpinnings, anxiety in humans seems to be mediated through a neuronal network, which involves several distinct brain regions, neuronal circuits and projections as well as neurotransmitters. A large body of evidence suggests that the neuropeptide cholecystokinin (CCK) might be an important modulator of this neuronal network. Key regions of the fear network, such as amygdala, hypothalamus, peraqueductal grey, or cortical regions seem to be connected by CCKergic pathways. CCK interacts with several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and noradrenergic system as well as with endocannabinoids, NPY and NPS. In humans, administration of CCK-4 reliably provokes panic attacks, which can be blocked by antipanic medication. Also, there is some support for a role of the CCK system in the genetic pathomechanism of PD with particularly strong evidence for the CCK gene itself and the CCK-2R (CCKBR) gene. Thus, it is hypothesized that genetic variants in the CCK system might contribute to the biological basis for the postulated CCK dysfunction in the fear network underlying PD. Taken together, a large body of evidence suggests a possible role for the neuropeptide CCK in PD with regard to neuroanatomical circuits, neurotransmitters and genetic factors. This review article proposes an extended hypothetical model for human PD, which integrates preclinical and clinical findings on CCK in addition to existing theories of the pathogenesis of PD.

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“…Initial analyses of a complete genome scan for panic disorder did not reveal evidence of significant linkage [Knowles et al, 1998]. In candidate gene studies, a variety of neurotransmitter and neuropeptide receptor genes have been tested and failed to show linkage to or association with the panic disorder phenotype [Crowe et al, 1987, 1997; Mutchler et al, 1990; Wang et al, 1992; Crawford et al, 1995; Kato et al, 1996; Ohara et al, 1996; Steinlein et al, 1997]. More recently, several nominally significant associations have been reported, though none have been established [Deckert et al, 1998, 1999; Rowe et al, 1998; Wang et al, 1998; Kennedy et al, 1999; Nakamura et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Genetic association analysis of behavioral inhibition using candidate loci from mouse models

et al. 2001

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Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci. We have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P = 0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin. This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders.

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Missense mutation of the cholecystokinin B receptor gene: Lack of association with panic disorder

Cited by 13 publications

References 0 publications

The genetics of panic disorder

The genetics of panic disorder

Neuronal Network of Panic Disorder: The Role of the Neuropeptide Cholecystokinin

Genetic association analysis of behavioral inhibition using candidate loci from mouse models

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