Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

Jony Sheynin; Elizabeth R. Duval; Anthony P. King; Mike Angstadt; K. Luan Phan; Naomi M. Simon; Sheila A.M. Rauch; Israel Liberzon

doi:10.1002/da.23075

Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

Jony Sheynin, Elizabeth R. Duval, Anthony P. King, Mike Angstadt, K. Luan Phan, Naomi M. Simon, Sheila A.M. Rauch, Israel Liberzon

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response.

METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN).

RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).

CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

Original language	English (US)
Pages (from-to)	1037-1046
Number of pages	10
Journal	Depression and Anxiety
Volume	37
Issue number	10
DOIs	https://doi.org/10.1002/da.23075
State	Published - Oct 1 2020

Keywords

PTSD
fMRI
functional connectivity
prolonged exposure
resting state
sertraline
Stress Disorders, Post-Traumatic/diagnostic imaging
Veterans
Humans
Connectome
Prefrontal Cortex
Brain/diagnostic imaging
Magnetic Resonance Imaging

ASJC Scopus subject areas

Psychiatry and Mental health
Clinical Psychology

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10.1002/da.23075

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title = "Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder",

abstract = "BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response.METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN).RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.",

keywords = "PTSD, fMRI, functional connectivity, prolonged exposure, resting state, sertraline, Stress Disorders, Post-Traumatic/diagnostic imaging, Veterans, Humans, Connectome, Prefrontal Cortex, Brain/diagnostic imaging, Magnetic Resonance Imaging",

author = "Jony Sheynin and Duval, {Elizabeth R.} and King, {Anthony P.} and Mike Angstadt and Phan, {K. Luan} and Simon, {Naomi M.} and Rauch, {Sheila A.M.} and Israel Liberzon",

note = "Publisher Copyright: Published 2020. This article is a U.S. Government work and is in the public domain in the USA.",

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doi = "10.1002/da.23075",

language = "English (US)",

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T1 - Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

AU - Sheynin, Jony

AU - Duval, Elizabeth R.

AU - King, Anthony P.

AU - Angstadt, Mike

AU - Phan, K. Luan

AU - Simon, Naomi M.

AU - Rauch, Sheila A.M.

AU - Liberzon, Israel

N1 - Publisher Copyright: Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response.METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN).RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

AB - BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response.METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN).RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042).CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.

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KW - sertraline

KW - Stress Disorders, Post-Traumatic/diagnostic imaging

KW - Veterans

KW - Humans

KW - Connectome

KW - Prefrontal Cortex

KW - Brain/diagnostic imaging

KW - Magnetic Resonance Imaging

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Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder

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