Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response

Rajapillai L.I. Pillai, Chuan Huang, Andrew LaBella, Mengru Zhang, Jie Yang, Madhukar H Trivedi, Myrna Weissman, Patrick McGrath, Maurizio Fava, Benji Kurian, Crystal Cooper Cortes, Melvin McInnis, Maria A. Oquendo, Diego A. Pizzagalli, Ramin V. Parsey, Christine DeLorenzo

Research output: Contribution to journalArticle

Abstract

Background: Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. Methods: 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. Results: Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. Conclusions: We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.

Original languageEnglish (US)
Pages (from-to)8-16
Number of pages9
JournalJournal of Affective Disorders
Volume256
DOIs
StatePublished - Sep 1 2019

Fingerprint

Anisotropy
Serotonin Uptake Inhibitors
Amygdala
Raphe Nuclei
Major Depressive Disorder
Placebos
Depression
Sertraline
Antidepressive Agents
Hippocampus
Biomarkers
Research

Keywords

  • Amygdala
  • Diffusion tensor imaging
  • Fractional anisotropy
  • Raphe nucleus
  • Remission
  • SSRI

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response. / Pillai, Rajapillai L.I.; Huang, Chuan; LaBella, Andrew; Zhang, Mengru; Yang, Jie; Trivedi, Madhukar H; Weissman, Myrna; McGrath, Patrick; Fava, Maurizio; Kurian, Benji; Cooper Cortes, Crystal; McInnis, Melvin; Oquendo, Maria A.; Pizzagalli, Diego A.; Parsey, Ramin V.; DeLorenzo, Christine.

In: Journal of Affective Disorders, Vol. 256, 01.09.2019, p. 8-16.

Research output: Contribution to journalArticle

Pillai, RLI, Huang, C, LaBella, A, Zhang, M, Yang, J, Trivedi, MH, Weissman, M, McGrath, P, Fava, M, Kurian, B, Cooper Cortes, C, McInnis, M, Oquendo, MA, Pizzagalli, DA, Parsey, RV & DeLorenzo, C 2019, 'Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response', Journal of Affective Disorders, vol. 256, pp. 8-16. https://doi.org/10.1016/j.jad.2019.05.055
Pillai, Rajapillai L.I. ; Huang, Chuan ; LaBella, Andrew ; Zhang, Mengru ; Yang, Jie ; Trivedi, Madhukar H ; Weissman, Myrna ; McGrath, Patrick ; Fava, Maurizio ; Kurian, Benji ; Cooper Cortes, Crystal ; McInnis, Melvin ; Oquendo, Maria A. ; Pizzagalli, Diego A. ; Parsey, Ramin V. ; DeLorenzo, Christine. / Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response. In: Journal of Affective Disorders. 2019 ; Vol. 256. pp. 8-16.
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abstract = "Background: Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. Methods: 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. Results: Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. Conclusions: We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.",
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T1 - Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response

AU - Pillai, Rajapillai L.I.

AU - Huang, Chuan

AU - LaBella, Andrew

AU - Zhang, Mengru

AU - Yang, Jie

AU - Trivedi, Madhukar H

AU - Weissman, Myrna

AU - McGrath, Patrick

AU - Fava, Maurizio

AU - Kurian, Benji

AU - Cooper Cortes, Crystal

AU - McInnis, Melvin

AU - Oquendo, Maria A.

AU - Pizzagalli, Diego A.

AU - Parsey, Ramin V.

AU - DeLorenzo, Christine

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. Methods: 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. Results: Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. Conclusions: We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.

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