Home LiteratureArticle Details
PMID: 14512209 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder.

Biological psychiatry ·Vol. 54 ·No. 7 ·2003-10-01 ·Pages 693-702

Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD

Abstract

Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Declarative memory was assessed with the Wechsler Memory Scale-Revised and Selective Reminding Test before and after 9-12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD.

MeSH Terms
Adult Brain Mapping Case-Control Studies Female Hippocampus/drug effects,physiology Humans Individuality Magnetic Resonance Imaging Male Memory/drug effects Middle Aged Neuropsychological Tests Paroxetine/therapeutic use Serotonin Uptake Inhibitors/therapeutic use Stress Disorders, Post-Traumatic/drug therapy,pathology,physiopathology Time Verbal Learning/drug effects Wechsler Scales
Chemicals
Serotonin Uptake Inhibitors Paroxetine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Vermetten Eric
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
Vythilingam Meena
Southwick Steven M
Charney Dennis S
Bremner J Douglas
References (63)
63 references, click to expand
  1. Hippocampal volume in women victimized by childhood sexual abuse.
    Psychol Med. 1997 Jul;27(4):951-9 PMID: 9234472
  2. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus.
    J Neurosci. 1995 Mar;15(3 Pt 1):1768-77 PMID: 7891134
  3. Selective reminding test: an examination of the equivalence of four forms.
    J Clin Exp Neuropsychol. 1985 Jun;7(3):251-63 PMID: 3998090
  4. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.
    Am J Psychiatry. 1994 Oct;151(10):1430-6 PMID: 7916539
  5. Concentration camp survivors in Denmark persecution, disease, disability, compensation. A 23-year follow-up. A survey of the long-term effects of severe environmental stress.
    Dan Med Bull. 1970 Mar-Apr;17(3):65-108 PMID: 5419248
  6. Learning and memory in rape victims with posttraumatic stress disorder.
    Am J Psychiatry. 1998 Feb;155(2):278-9 PMID: 9464211
  7. The timing, triggers and qualities of recovered memories in therapy.
    Br J Clin Psychol. 2000 Mar;39 ( Pt 1):11-26 PMID: 10789025
  8. Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial.
    J Clin Psychiatry. 2001 Nov;62(11):860-8 PMID: 11775045
  9. Attention and memory dysfunction in posttraumatic stress disorder.
    Neuropsychology. 1998 Jan;12(1):125-33 PMID: 9460740
  10. Cognitive deficits and psychopathology among former prisoners of war and combat veterans of the Korean conflict.
    Am J Psychiatry. 1991 Jan;148(1):67-72 PMID: 1984709
  11. Deficits in short-term memory in adult survivors of childhood abuse.
    Psychiatry Res. 1995 Nov 29;59(1-2):97-107 PMID: 8771224
  12. Why stress is bad for your brain.
    Science. 1996 Aug 9;273(5276):749-50 PMID: 8701325
  13. Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder.
    Psychiatry Res. 2003 Apr 1;122(3):193-8 PMID: 12694893
  14. Childhood trauma associated with smaller hippocampal volume in women with major depression.
    Am J Psychiatry. 2002 Dec;159(12):2072-80 PMID: 12450959
  15. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder.
    Biol Psychiatry. 1996 Dec 1;40(11):1091-9 PMID: 8931911
  16. Attention and regional cerebral blood flow in posttraumatic stress disorder patients with substance abuse histories.
    Psychiatry Res. 1996 May 31;67(1):17-28 PMID: 8797239
  17. Circuits and systems in stress. I. Preclinical studies.
    Depress Anxiety. 2002;15(3):126-47 PMID: 12001181
  18. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.
    Biol Psychiatry. 1999 Dec 15;46(12):1595-602 PMID: 10624540
  19. Phenytoin prevents stress- and corticosterone-induced atrophy of CA3 pyramidal neurons.
    Hippocampus. 1992 Oct;2(4):431-5 PMID: 1308199
  20. Deficits in short-term memory in posttraumatic stress disorder.
    Am J Psychiatry. 1993 Jul;150(7):1015-9 PMID: 8317569
  21. Comparison of Neuropsychological Test Performance in PTSD, Generalized Anxiety Disorder, and Control Vietnam Veterans
    Assessment. 1994 Jun;1(2):133-42 PMID: 9465143
  22. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.
    J Neurosci. 1996 Apr 1;16(7):2365-72 PMID: 8601816
  23. Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study.
    Am J Psychiatry. 2001 Dec;158(12):1982-8 PMID: 11729013
  24. Loss of brain volume in endogenous Cushing's syndrome and its reversibility after correction of hypercortisolism.
    J Clin Endocrinol Metab. 2002 May;87(5):1949-54 PMID: 11994323
  25. Improvement in learning associated with increase in hippocampal formation volume.
    Biol Psychiatry. 2003 Feb 1;53(3):233-8 PMID: 12559656
  26. Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms.
    J Trauma Stress. 2001 Jul;14(3):445-52 PMID: 11534876
  27. Everyday memory deficits in children and adolescents with PTSD: performance on the Rivermead Behavioural Memory Test.
    J Child Psychol Psychiatry. 1999 Mar;40(3):357-61 PMID: 10190337
  28. Complaints of impaired memory in veterans with PTSD.
    Am J Psychiatry. 2001 Oct;158(10):1738-9 PMID: 11579019
  29. Regulation of adult neurogenesis by antidepressant treatment.
    Neuropsychopharmacology. 2001 Dec;25(6):836-44 PMID: 11750177
  30. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation.
    J Neurosci. 1997 Apr 1;17(7):2492-8 PMID: 9065509
  31. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma.
    Nat Neurosci. 2002 Nov;5(11):1242-7 PMID: 12379862
  32. Stress activation of glutamate neurotransmission in the prefrontal cortex: implications for dopamine-associated psychiatric disorders.
    Biol Psychiatry. 2002 May 15;51(10):775-87 PMID: 12007451
  33. Hippocampal damage associated with prolonged glucocorticoid exposure in primates.
    J Neurosci. 1990 Sep;10(9):2897-902 PMID: 2398367
  34. Paradoxical effects of adrenal steroids on the brain: protection versus degeneration.
    Biol Psychiatry. 1992 Jan 15;31(2):177-99 PMID: 1737079
  35. Verbal memory impairment correlates with hippocampal pyramidal cell density.
    Neurology. 1990 Nov;40(11):1694-7 PMID: 2234424
  36. Learning and memory in combat veterans with posttraumatic stress disorder.
    Am J Psychiatry. 1995 Jan;152(1):137-9 PMID: 7802106
  37. Post-traumatic stress disorder, hormones, and memory.
    Biol Psychiatry. 1989 Jul;26(3):221-3 PMID: 2545287
  38. Attention, learning, and memory performances and intellectual resources in Vietnam veterans: PTSD and no disorder comparisons.
    Neuropsychology. 2002 Jan;16(1):5-14 PMID: 11853357
  39. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.
    Am J Psychiatry. 1995 Jul;152(7):973-81 PMID: 7793467
  40. Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans.
    Am J Psychiatry. 1993 Feb;150(2):235-9 PMID: 8422073
  41. Fluoxetine increases the content of neurotrophic protein S100beta in the rat hippocampus.
    Eur J Pharmacol. 2001 May 25;420(2-3):R1-2 PMID: 11408041
  42. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.
    J Neurosci. 2000 Dec 15;20(24):9104-10 PMID: 11124987
  43. Multivariate assessment of explicit memory function in combat veterans with posttraumatic stress disorder.
    J Trauma Stress. 2001 Apr;14(2):413-32 PMID: 11469166
  44. Information processing and PTSD: a review of the empirical literature.
    Clin Psychol Rev. 2000 Nov;20(8):1041-65 PMID: 11098399
  45. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine.
    Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12796-801 PMID: 11675510
  46. An open trial of paroxetine in patients with noncombat-related, chronic posttraumatic stress disorder.
    J Clin Psychopharmacol. 1998 Feb;18(1):10-8 PMID: 9472837
  47. Stress, memory, and the hippocampus: can't live with it, can't live without it.
    Behav Brain Res. 2001 Dec 14;127(1-2):137-58 PMID: 11718889
  48. Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8856-61 PMID: 11447269
  49. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.
    J Neurosci. 1995 Nov;15(11):7539-47 PMID: 7472505
  50. Effect of chronic antidepressant treatment on transcription factor binding activity in rat hippocampus and frontal cortex.
    Prog Neuropsychopharmacol Biol Psychiatry. 1998 Jul;22(5):787-802 PMID: 9723120
  51. Test-retest reliability of the Wechsler Memory Scale, Form I.
    J Clin Psychol. 1981 Oct;37(4):847-8 PMID: 7309876
  52. The development of a Clinician-Administered PTSD Scale.
    J Trauma Stress. 1995 Jan;8(1):75-90 PMID: 7712061
  53. Performance of PTSD patients on standard tests of memory. Implications for trauma.
    Ann N Y Acad Sci. 1997 Jun 21;821:208-18 PMID: 9238205
  54. Analyze: a comprehensive, operator-interactive software package for multidimensional medical image display and analysis.
    Comput Med Imaging Graph. 1989 Nov-Dec;13(6):433-54 PMID: 2688869
  55. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity.
    Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1852-7 PMID: 9465106
  56. Longitudinal study of brain morphology in first episode schizophrenia.
    Biol Psychiatry. 2001 Mar 15;49(6):487-99 PMID: 11257234
  57. Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.
    Biol Psychiatry. 2002 Jul 15;52(2):119-25 PMID: 12114003
  58. Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate.
    Brain Res. 1994 Aug 29;655(1-2):251-4 PMID: 7812782
  59. Effects of practice in repeated administrations of the Wechsler Memory Scale Revised in normal adults.
    Assessment. 1998 Mar;5(1):85-92 PMID: 9458344
  60. Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse--a preliminary report.
    Biol Psychiatry. 1997 Jan 1;41(1):23-32 PMID: 8988792
  61. Neuropsychological findings in combat-related posttraumatic stress disorder.
    Clin Neuropsychol. 2002 Aug;16(3):310-21 PMID: 12607144
  62. Development and preliminary psychometric properties of an instrument for the measurement of childhood trauma: the Early Trauma Inventory.
    Depress Anxiety. 2000;12(1):1-12 PMID: 10999240
  63. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3168-71 PMID: 9501234
Article Info
Journal
Biological psychiatry
Abbr.
Biol Psychiatry
ISSN
0006-3223
DOI
10.1016/s0006-3223(03)00634-6
Published
2003-10-01
Pages
693-702
Language
English
Region
United States
NLM ID
0213264
PMCID
PMC3233762
Subset
IM
Grants
NIMH NIH HHS · R01 MH056120 · United States
NIMH NIH HHS · R01 MH056120-04 · United States
NIMH NIH HHS · R01 MH56120 · United States
External Links
PubMed source DOI: 10.1016/s0006-3223(03)00634-6 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2