Comorbid Migraine with Aura, Anxiety, and Depression Is Associated with Dopamine D2 Receptor (DRD2) NcoI Alleles

Peroutka, Stephen J.; Price, Susan; Wilhoit, Tara L.; Jones, Keith

doi:10.1007/bf03401725

Cited by 121 publications

(85 citation statements)

References 52 publications

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“…Genetic, epidemiologic and clinical data confirm this association [6][7][8][9]. Cephalalgiaphobia can be possibly classified as an anxiety disorder, under the heading of specific phobias, different from other specific phobias.…”

Section: Discussionmentioning

confidence: 88%

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Cephalalgiaphobia: a possible specific phobia of illness

et al. 2007

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Psychiatric comorbidity, mainly anxiety and depression, are common in chronic migraine (CM). Phobias are reported by half of CM patients. Phobic avoidance associated with fear of headache or migraine attack has never been adequately described. We describe 12 migraine patients with particular phobic-avoidant behaviours related to their headache attacks, which we classified as a specific illness phobia, coined as cephalalgiaphobia. All patients were women, mean age 42, and all had a migraine diagnosis (11 CM, all overused acute medications). Patients had either a phobia of a headache attack during a pain-free state or a phobia of pain worsening during mild headache episodes. Patients overused acute medication as phobic avoidance. It is a significant problem, associated with distress and impairment, interfering with medical care.Cephalalgiaphobia is a possible specific phobia of illness, possibly linked to progression of migraine to CM and to acute medication overuse headache.

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Section: Discussionmentioning

confidence: 88%

“…Social phobia is three-fold more common in migraineurs than in controls [8]. Phobias and migraines were linked genetically via the DRD2 dopamine receptor allele [9].…”

Section: Introductionmentioning

confidence: 99%

Cephalalgiaphobia: a possible specific phobia of illness

et al. 2007

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“…In addition, high platelet levels of dopamine have been observed in migraineurs (D'Andrea et al 2006). Several association studies on D 2 -like receptors and migraine with or without aura have been reported, but with contradictory results (Maude et al 2001;Mochi et al 2003;Peroutka et al 1998;Peroutka et al 1997). Thus, it appears that if dopamine and its receptors are at all involved in the pathophysiology of migraine, the exact mechanism of action still remains unclear.…”

Section: Dopamine Receptorsmentioning

confidence: 99%

Current and prospective pharmacological targets in relation to antimigraine action

Mehrotra

Gupta

Chan

et al. 2008

Naunyn-Schmied Arch Pharmacol

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Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT 1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT 2 receptor antagonists, Ca 2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT 1-7 ), adrenergic (α 1 , α 2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP 2 ), adenosine (A 1 , A 2 , and A 3 ), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon.

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“…[9][10][11][12][13][14][22][23][24][25][26] By genotyping about 200 controls and patients with prolactinomas, we found similar allelic frequencies of TaqI A1/A2, TaqI B1/B2, HphI G/T and NcoI C/T in the two groups that were comparable to those of European and American populations (NCBI, Entrez SNP database, TaqI A: http:// www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs ¼ 1800497; TaqI B: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs ¼ 1079597; HphI:…”

Section: Filopanti Et Almentioning

confidence: 99%

“…Due to the critical role of dopaminergic activity in the central nervous system, several studies examined the association between common polymorphisms of the DRD2 gene and behavioral traits, psychiatric and neurological diseases, such as schizophrenia, alcoholism, smoking, opioids and polysubstance abuse, and susceptibility to migraine. [9][10][11][12][13][14] Accordingly, in vivo evidence supporting the potential functional significance of DRD2 variants has been accumulating. In particular, previous studies reported the association of DRD2 TaqI A, TaqI B and NcoI polymorphisms with modifications in D2 receptor binding and expression in human central nervous system, particularly in the striatum.…”

Section: Introductionmentioning

confidence: 99%

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

et al. 2008

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Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P ¼ 0.038) and tumor shrinkage (70.4 vs 41.4%, P ¼ 0.006). Finally, [TaqI A1À/TaqI B1À/HphI TÀ/NcoI TÀ] haplotype was found in 34.5% of patients normalizing PRL with p3 mg/ week of CB vs 11.3% of resistants (P ¼ 0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T þ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.

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Comorbid Migraine with Aura, Anxiety, and Depression Is Associated with Dopamine D2 Receptor (DRD2) NcoI Alleles

Abstract: These data indicate that MWA, anxiety disorders, and major depression can be components of a distinct clinical syndrome associated with allelic variations within the DRD2 gene. Clinical recognition of this genetically based syndrome has significant diagnostic and therapeutic implications.

Cited by 121 publications

References 52 publications

Cephalalgiaphobia: a possible specific phobia of illness

Cephalalgiaphobia: a possible specific phobia of illness

Current and prospective pharmacological targets in relation to antimigraine action

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

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