title: Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates.
abstract: BACKGROUND
  Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and other disorders. However, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed SSRIs for non-mood disorders. Here we evaluated SSRI effects on neural volumetrics in depressed and nondepressed monkeys.
  
  
  METHODS
  42 socially-housed cynomolgus monkeys were randomized to treatment balanced on pretreatment depressive behavior and body weight. Monkeys were trained for oral administration of placebo or 20 mg/kg sertraline HCl daily for 18 months and depressive and anxious behavior recorded. Volumes of neural regions of interest in depression were measured in magnetic resonance images and analyzed by 2 (depressed, nondepressed)×2 (placebo, sertraline) ANOVA.
  
  
  RESULTS
  Sertraline reduced anxiety (p=0.04) but not depressive behavior (p=0.43). Left Brodmann's Area (BA) 32 was smaller in depressed than nondepressed monkeys (main effect of depression: p<0.05). Sertraline and depression status interacted to affect volumes of left Anterior Cingulate Cortex (ACC), left BA24, right hippocampus (HC), and right anterior HC (sertraline×depression interactions: all p's<0.05). In the Placebo group, depressed monkeys had smaller right anterior HC and left ACC than nondepressed monkeys. In nondepressed monkeys, sertraline reduced right HC volume, especially right anterior HC volume. In depressed monkeys sertraline increased left ACC volume. In nondepressed monkeys, sertraline reduced left BA24 volumes resulting in smaller BA24 volumes in nondepressed than sertraline-treated depressed monkeys.
  
  
  CONCLUSIONS
  These observations suggest that SSRIs may differentially affect neural structures in depressed and nondepressed individuals.
authors.affiliation: Center for Neurobiology and Behavior, University of Pennsylvania, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Willard
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Uberseder
authors.affiliation: Neuroscience Graduate Program, Wake Forest School of Medicine, USA.
authors.forename: Ashlee
authors.initials: A
authors.lastname: Clark
authors.affiliation: Department of Physiology & Pharmacology, Wake Forest School of Medicine, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Daunais
authors.affiliation: Integrated Physiology and Pharmacology Program, Wake Forest School of Medicine, USA.
authors.forename: Warwick D
authors.initials: WD
authors.lastname: Johnston
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, USA.
authors.forename: David
authors.initials: D
authors.lastname: Neely
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, USA.
authors.forename: Adreanna
authors.initials: A
authors.lastname: Massey
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, USA.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.affiliation: Department of Biomedical Engineering, Wake Forest School of Medicine, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kraft
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, USA.
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.affiliation: Department of Physiology & Pharmacology, Wake Forest School of Medicine, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, USA. Electronic address: cshively@wakehealth.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Shively
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D009929:Organ Size; D011897:Random Allocation; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D020280:Sertraline / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D006897:Hydroxyindoleacetic Acid; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C065162:desmethylsertraline
keywords: Anterior Cingulate Cortex; Depression; Hippocampus; MRI; Nonhuman primate; SSRI