Comorbid migraine with aura, anxiety, and depression is associated with dopamine D2 receptor (DRD2) NcoI alleles.
BACKGROUND
Unrelated individuals (n = 242) were interviewed directly for the presence of migraine, anxiety disorders, and major depression.


METHODS
The data described in this study are derived from a clinical genetic relational database that was developed initially for the genetic analysis of migraine. Genotyping of the DRD2 NcoI C to T polymorphism located in exon 6 (His313His) was performed using previously described primers.


RESULTS
A significantly increased incidence of migraine with aura (MWA), major depression, generalized anxiety disorder (GAD), panic attacks, and phobia was observed in individuals with the DRD2 NcoI C/C genotype compared with individuals with an DRD2 NcoI T allele. Specifically, 69% (91/131) of DRD2 NcoI C/C individuals in the present study met criteria for at least one of these neuropsychiatric disorders versus only 22% (4/18) of the DRD2 NcoI T/T individuals (Chi-square = 15.29; p < 0.00005). The DRD2 NcoI C allele frequency is significantly higher (Chi-square = 17.13; p < 0.00002) in individuals with MWA, anxiety disorders, and/or major depression (C allele frequency = 0.80) than in individuals who have none of these disorders (C allele frequency = 0.67).


CONCLUSIONS
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.
Peroutka
S J
SJ
Spectra Biomedical Inc., Burlingame, CA 94010, USA. DrPeroutka@aol.com
Price
S C
SC
Wilhoit
T L
TL
Jones
K W
KW
D000483:Alleles; D001008:Anxiety Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008881:Migraine Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011954:Receptors, Dopamine / Q000235:genetics*
D011954:Receptors, Dopamine; C052380:endodeoxyribonuclease NcoI; D015252:Deoxyribonucleases, Type II Site-Specific