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Cited by 25Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates

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Willard, Stephanie L., Uberseder, Beth, Clark, Ashlee, Daunais, James B., Johnston, Warwick D., Neely, David, Massey, Adreanna, Williamson, Jeff D. +4 more·2015·Neuropharmacology
DOI 10.1016/j.neuropharm.2015.06.011PMC PMC4655145
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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.

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  • SSRI treatment increases gray matter volume in a nonhuman primate depression model.

    “Nevertheless, treatment with SSRIs was demonstrated to increase GMV in healthy human subjects (Kraus et al., 2014), in a depression model of nonhuman primates (Willard et al., 2015), and in depressive patients (Smith et al., 2013; see Table 2).”

    From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Willard et al., 2015

    The Results (§3.4; page not provided) report that sertraline-treated depressed monkeys had larger left anterior cingulate cortex volumes than placebo-treated depressed monkeys. The claim describes this as an increase in gray matter volume, but the paper reports regional volume and notes that its manual segmentation did not finely distinguish gray from white matter. (LLM, conf=0.85)

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Research works printed but not linked: 1

  1. Amaral D Lavenex P Anderson P Morris R Amaral D Bliss T O’Keefe J Hippocampal neuroanatomy The Hippocampus Book 2007 New York Oxford University Press 37 114

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Authors
Willard, S. L., Uberseder, B., Clark, A., Daunais, J. B., Johnston, W. D., Neely, D., Massey, A., Williamson, J. D., Kraft, R. A., Bourland, J. D., Jones, S. R., & Shively, C. A.
Affiliations
  • University of Pennsylvania (US)
  • Wake Forest University Health Sciences (US)
  • Wake Forest University (US)
Corresponding author
Shively, Carol A.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2015-12
Volume
99
Pages
369-378
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2015.06.011
PMC
PMC4655145
OpenAlex
W998838816
Cited by
25
References
81
Citations by year
2026: 2 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 5 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 4
FWCI
2.16
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (HL087103)
  • Roena Kulynych Center for Memory and Cognition Research
  • Translational Science Institute of Wake Forest School of Medicine
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
sertraline, selective serotonin reuptake inhibitors, depression, Macaca fascicularis, anterior cingulate cortex, hippocampus, anxiety, long-term drug effects, brain structure
MeSH terms
Administration, Oral, Animals, Antidepressive Agents, Anxiety, Behavior, Animal, Brain, Depressive Disorder, Female, Hydroxyindoleacetic Acid, Macaca fascicularis, Magnetic Resonance Imaging, Organ Size, Random Allocation, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Sertraline

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