Molecular imaging of the serotonin transporter availability and occupancy by antidepressant treatment in late-life depression

NEUROPHARMACOLOGY

卷:194

Article

Smith, Gwenn S.^1,2  Kuwabara, Hiroto²  Gould, Neda F.¹  Nassery, Najilla³  Savonenko, Alena⁴  Joo, Jin Hui¹  Bigos, Kristin L.^5,6  Kraut, Michael⁷  Brasic, James²  Holt, Daniel P.²  Hall, Andrew W.²  Mathews, William B.²  Dannals, Robert F.²  Nandi, Ayon²  Workman, Clifford I.¹ 

[1] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Nucl Med & Mol Imaging, Baltimore, MD USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Neuroradiol, Baltimore, MD USA

关键词: Selective serotonin reuptake inhibitors;    Citalopram;    Sertraline;    Serotonin transporter;    Positron emission tomography (PET);    Late-life depression;    Aging;   

DOI  :  10.1016/j.neuropharm.2021.108447

来源: Elsevier

【 摘 要 】

Patients with late-life depression (LLD) have a more variable response to pharmacotherapy relative to patients with mid-life depression. Degeneration of the serotonergic system and lower occupancy of the initial target for antidepressant medications, the serotonin transporter (5-HTT), may contribute to variability in treatment response. The focus of this study was to test the hypotheses that lower cortical and limbic serotonin transporter (5-HTT) availability in LLD patients relative to controls and less 5-HTT occupancy by antidepressant medications would be associated with less improvement in mood and cognition with treatment in LLD patients. Twenty LLD patients meeting DSM-IV criteria for a current major depressive episode and 20 non-depressed controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes and high-resolution positron emission tomography (PET) scanning to measure 5-HTT before and after 10-12 weeks of treatment with Citalopram or Sertraline (patients only). Prior to treatment, 5-HTT was lower in LLD patients relative to controls in mainly temporal cortical and limbic (amygdala and hippocampus) regions. Gray matter volumes were not significantly different between groups. 5-HTT occupancy was detected throughout cortical, striatal, thalamic and limbic regions. The magnitude of regional 5-HTT occupancy by antidepressants was 70% or greater across cortical and sub-cortical regions, consistent with the magnitude of 5-HTT occupancy observed in mid-life depressed patients. Greater regional 5-HTT occupancy correlated with greater improvement in depressive symptoms and visual-spatial memory performance. These data support the hypothesis that serotonin degeneration and variability in 5-HTT occupancy may contribute to heterogeneity in treatment response in LLD patients.

【 授权许可】

Free