Elsevier

Neuroscience Letters

Volume 491, Issue 3, 24 March 2011, Pages 196-201
Neuroscience Letters

Increased neural response to trauma scripts in posttraumatic stress disorder following paroxetine treatment: A pilot study

https://doi.org/10.1016/j.neulet.2011.01.037Get rights and content

Abstract

Neuroimaging studies of individuals with posttraumatic stress disorder (PTSD) have revealed altered patterns of activity in medial prefrontal brain regions, including the anterior cingulate cortex (ACC), an area implicated in affect regulation. Selective serotonin reuptake inhibitors (SSRIs) have been shown to effectively treat PTSD symptoms, but there remains a lack of functional neuroimaging research examining the effects of psychopharmacological treatment on brain function in PTSD. The purpose of this pilot study was to assess the effects of the SSRI paroxetine on neural responses to traumatic memories in a small sample of patients with PTSD, as measured with PET imaging; we hypothesized that paroxetine treatment would be associated with increased regional cerebral blood flow (rCBF) in the medial prefrontal cortex. Thirteen participants with PTSD were given controlled-release paroxetine (paroxetine CR) or placebo in a randomized, double-blind fashion for 12 weeks. Participants underwent brain imaging using positron emission tomography (PET) before and at the end of treatment in conjunction with exposure to neutral scripts and personalized trauma scripts. Participants treated with paroxetine CR and placebo both exhibited significantly increased rCBF in the ACC during trauma versus neutral script presentations; however, we noted an increase in function in the orbitofrontal cortex (OFC) in paroxetine-treated (but not placebo-treated) participants. Participants in both groups showed decreases in overall PTSD symptomatology following treatment; paroxetine-treated participants showed a slightly greater percentage decrease in symptoms. These preliminary findings indicate that increased ACC function represents a nonspecific response to treatment, whereas increased OFC function is specifically associated with paroxetine treatment in PTSD. These pilot data reveal putative mechanisms for SSRI treatment in PTSD and substantiate the need for large-scale placebo-controlled studies investigating these effects.

Research highlights

► Paroxetine, but not placebo, treatment is associated with increased OFC activation. ► Paroxetine and placebo treatments are both associated with increased activation in the ACC. ► SSRI treatment may act more specifically on orbitofrontal circuits that modulate fear extinction. ► These pilot data reveal putative mechanisms for SSRI treatment in PTSD. ► Our findings substantiate the need for further imaging studies of SSRI treatment in PTSD.

Section snippets

Acknowledgments

This study was supported by an Investigator Initiated Research Grant from GlaxoSmithKline and NIH research grants to JDB R01 HL088726, K24 MH076955, T32 MH067547-01, R01 MH56120, and the clinical interactions network (CIN) of the Atlanta Clinical and Translational Sciences Institute (ACTSI). We wish to acknowledge Sinead Quinn, Delicia Votaw, C.N.M.T. and Margie Jones, C.N.M.T., for their assistance with imaging and analysis procedures.

References (29)

  • D.D. Blake et al.

    The development of a clinician-administered PTSD scale

    J. Trauma. Stress

    (1995)
  • J.D. Bremner

    Traumatic stress: effects on the brain

    Dialogues Clin. Neurosci.

    (2006)
  • J.D. Bremner et al.

    Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse

    Arch. Gen. Psychiatry

    (1997)
  • J.D. Bremner et al.

    Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder

    Am. J. Psychiatry

    (1999)
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