title: Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates.
abstract: OBJECTIVE
  Major depressive disorder and coronary heart disease often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on coronary heart disease risk remain unclear. We determined the effects of an SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA.
  
  
  METHODS
  Forty-two adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase and assigned to SSRI (sertraline hydrochloride 20 mg/kg, per os, once a day) or placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months, CAA extent was measured using histomorphometry.
  
  
  RESULTS
  Before and during treatment, depressed monkeys had lower BW, body mass index, and plasma high-density lipoprotein cholesterol, and higher heart rates during the pretreatment (p < .01) but not the treatment phase (p = .17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, body mass index, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (depressed, nondepressed) × 2 (placebo, sertraline) × 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than in nondepressed monkeys (p < .036), and in sertraline than in placebo-treated monkeys (p = .040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than that in untreated depressed monkeys, and 6.5 times higher than that in nondepressed monkeys, on average.
  
  
  CONCLUSIONS
  Depressed animals developed more CAA, and long-term treatment with sertraline resulted in more extensive CAA.
authors.affiliation: From the Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Shively
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: Susan E
authors.initials: SE
authors.lastname: Appt
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Clarkson
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology* / Q000473:pathology; D001522:Behavior, Animal; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D004195:Disease Models, Animal; D005260:Female; D007083:Iliac Artery / Q000473:pathology; D008137:Longitudinal Studies; D008252:Macaca fascicularis; D017697:Premenopause; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
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