Effect of depression and sertraline treatment on cardiac function in female nonhuman primates.
OBJECTIVE
Depression is a proposed risk factor for heart failure based largely on epidemiological data; few experimental data addressing this hypothesis are available.


METHODS
Depression was evaluated in relation to cardiac structural and functional phenotypes assessed by transthoracic echocardiography in 42 adult female cynomolgus monkeys that consumed a Western-like diet for 3 years. Half of the monkeys were treated with sertraline HCl for 18 months, and depressive behavior was assessed for 12 months before echocardiography.


RESULTS
Depressed monkeys (the 19/42 with depressive behavior rates above the mean rate) had higher heart rates (HRs; 171 [4.1[ versus 152 [6.1]) and smaller body surface area (0.13 [0.003] versus 0.15 [0.004]), left ventricular (LV) end-systolic dimension (0.75 [0.05] versus 0.89 [0.04]), LV systolic (0.76 [0.08] versus 1.2 [0.11]) and diastolic (2.4 [0.23] versus 3.4 [0.26]) volumes, and left atrial volumes (1.15 [0.14] versus 1.75 [0.12]; p values < .05). Doppler profiles of depressed monkeys indicated greater myocardial relaxation (higher e' and higher e'/a' ratio) and lower filling pressures (lower E/e') compared to nondepressed monkeys (p values < .05). Although sertraline treatment reduced HR (150 [5.8] versus 171 [4.8]) and modestly increased chamber dimensions (LV end-systolic dimension: 0.91 [0.05] versus 0.74 [0.03]; LV end-diastolic dimension, body surface area adjusted 1.69 [0.05] versus 1.47 [0.06]; p values < .05), it did not overtly affect systolic or diastolic function (p values > .10).


CONCLUSIONS
These data suggest that behavioral depression in female primates is accompanied by differences in cardiac function, although not in ways classically associated with subclinical heart failure. Selective serotonin reuptakes show promise in supporting heart function by reducing HR and perhaps improving LV filling; however, further investigation is needed.
Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1040. cshively@wakehealth.edu.
Leanne
L
Groban
Dalane W
DW
Kitzman
Thomas C
TC
Register
Carol A
CA
Shively
D000704:Analysis of Variance; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology; D001837:Body Weights and Measures; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology / Q000503:physiopathology*; D004032:Diet; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008252:Macaca fascicularis; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010919:Placebos; D011897:Random Allocation; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*
D006897:Hydroxyindoleacetic Acid; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
CSF; SSRI; cardiac function; females; nonhuman primates; sertraline