Major depression and coronary flow reserve detected by positron emission tomography.
BACKGROUND
Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue.


METHODS
We examined 289 male middle-aged twins, including 106 twins (53 twin pairs) discordant for a lifetime history of MDD and 183 control twins (unrelated to any twins in the experimental group) without MDD. To calculate CFR, we used positron emission tomography with nitrogen 13 ((13)N) ammonia to evaluate myocardial blood flow at rest and after adenosine stress. A standard perfusion defect score was also used to assess myocardial ischemia.


RESULTS
There was no difference in myocardial ischemia between twins with and without MDD. Among the dizygotic twin pairs discordant for MDD, the CFR was 14% lower in the twins with MDD than in their brothers without MDD (2.36 vs 2.74) (P = .03). This association was not present in the monozygotic discordant pairs who were genetically matched (2.86 vs 2.64) (P = .19). The zygosity-MDD interaction after adjustment was significant (P = .006). The CFR in the dizygotic twins with MDD was also lower than in the control twins.


CONCLUSIONS
Our results provide evidence for a shared genetic pathway between MDD and microvascular dysfunction. Common pathophysiologic processes may link MDD and early atherosclerosis.
Vaccarino
Viola
V
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30306, USA. viola.vaccarino@emory.edu
Votaw
John
J
Faber
Tracy
T
Veledar
Emir
E
Murrah
Nancy V
NV
Jones
Linda R
LR
Zhao
Jinying
J
Su
Shaoyong
S
Goldberg
Jack
J
Raggi
J Paolo
JP
Quyyumi
Arshed A
AA
Sheps
David S
DS
Bremner
J Douglas
JD
D003324:Coronary Artery Disease / Q000235:genetics / Q000503:physiopathology; D003326:Coronary Circulation; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000235:genetics / Q000503:physiopathology*; D004200:Diseases in Twins / Q000235:genetics / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics / Q000503:physiopathology; D018384:Oxidative Stress; D049268:Positron-Emission Tomography; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic