Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression: Findings From the EMBARC Study

Jay C. Fournier, Henry W. Chase, Tsafrir Greenberg, Amit Etkin, Jorge R. Almeida, Richelle Stiffler, Thilo Deckersbach, Sarah Weyandt, Crystal Cooper, Marisa Toups, Tom Carmody, Benji Kurian, Scott Peltier, Phillip Adams, Melvin G. McInnis, Maria A. Oquendo, Patrick J. McGrath, Maurizio Fava, Myrna Weissman, Ramin ParseyMadhukar H. Trivedi, Mary L. Phillips

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background Personality dysfunction represents one of the only predictors of differential response between active treatments for depression to have replicated. We examine whether depressed patients with higher neuroticism scores, a marker of personality dysfunction, show differences compared with depressed patients with lower scores in the functioning of two brain regions associated with treatment response, the anterior cingulate and anterior insula cortices. Methods Functional magnetic resonance imaging data during an emotional Stroop task were collected from 135 adults with major depressive disorder at four academic medical centers participating in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) study. Secondary analyses were conducted including a sample of 28 healthy subjects. Results In whole-brain analyses, higher neuroticism among adults with depression was associated with increased activity in and connectivity with the right anterior insula cortex to incongruent compared with congruent emotional stimuli (all k ≥ 281, all p < .05 familywise error corrected), covarying for concurrent psychiatric distress. We also observed an unanticipated relationship between neuroticism and reduced activity in the precuneus (k = 269, p < .05 familywise error corrected). Exploratory analyses including healthy subjects suggested that associations between neuroticism and brain function may be nonlinear over the full range of neuroticism scores. Conclusions This study provides convergent evidence for the importance of the right anterior insula cortex as a brain-based marker of clinically meaningful individual differences in neuroticism among adults with depression. This is a critical next step in linking personality dysfunction, a replicated clinical predictor of differential antidepressant treatment response, with differences in underlying brain function.

Original languageEnglish (US)
Pages (from-to)138-148
Number of pages11
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Volume2
Issue number2
DOIs
StatePublished - Mar 1 2017

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Individuality
Antidepressive Agents
Depression
Brain
Personality
Healthy Volunteers
Parietal Lobe
Gyrus Cinguli
Major Depressive Disorder
Psychiatry
Neuroticism
Clinical Studies
Therapeutics
Magnetic Resonance Imaging

Keywords

  • Emotion regulation
  • fMRI
  • Major depressive disorder
  • Neuroticism
  • Precuneus
  • Right anterior insula

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology
  • Cognitive Neuroscience
  • Biological Psychiatry

Cite this

Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression : Findings From the EMBARC Study. / Fournier, Jay C.; Chase, Henry W.; Greenberg, Tsafrir; Etkin, Amit; Almeida, Jorge R.; Stiffler, Richelle; Deckersbach, Thilo; Weyandt, Sarah; Cooper, Crystal; Toups, Marisa; Carmody, Tom; Kurian, Benji; Peltier, Scott; Adams, Phillip; McInnis, Melvin G.; Oquendo, Maria A.; McGrath, Patrick J.; Fava, Maurizio; Weissman, Myrna; Parsey, Ramin; Trivedi, Madhukar H.; Phillips, Mary L.

In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol. 2, No. 2, 01.03.2017, p. 138-148.

Research output: Contribution to journalArticle

Fournier, JC, Chase, HW, Greenberg, T, Etkin, A, Almeida, JR, Stiffler, R, Deckersbach, T, Weyandt, S, Cooper, C, Toups, M, Carmody, T, Kurian, B, Peltier, S, Adams, P, McInnis, MG, Oquendo, MA, McGrath, PJ, Fava, M, Weissman, M, Parsey, R, Trivedi, MH & Phillips, ML 2017, 'Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression: Findings From the EMBARC Study', Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 2, no. 2, pp. 138-148. https://doi.org/10.1016/j.bpsc.2016.11.008
Fournier, Jay C. ; Chase, Henry W. ; Greenberg, Tsafrir ; Etkin, Amit ; Almeida, Jorge R. ; Stiffler, Richelle ; Deckersbach, Thilo ; Weyandt, Sarah ; Cooper, Crystal ; Toups, Marisa ; Carmody, Tom ; Kurian, Benji ; Peltier, Scott ; Adams, Phillip ; McInnis, Melvin G. ; Oquendo, Maria A. ; McGrath, Patrick J. ; Fava, Maurizio ; Weissman, Myrna ; Parsey, Ramin ; Trivedi, Madhukar H. ; Phillips, Mary L. / Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression : Findings From the EMBARC Study. In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2017 ; Vol. 2, No. 2. pp. 138-148.
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AU - Etkin, Amit

AU - Almeida, Jorge R.

AU - Stiffler, Richelle

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N2 - Background Personality dysfunction represents one of the only predictors of differential response between active treatments for depression to have replicated. We examine whether depressed patients with higher neuroticism scores, a marker of personality dysfunction, show differences compared with depressed patients with lower scores in the functioning of two brain regions associated with treatment response, the anterior cingulate and anterior insula cortices. Methods Functional magnetic resonance imaging data during an emotional Stroop task were collected from 135 adults with major depressive disorder at four academic medical centers participating in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) study. Secondary analyses were conducted including a sample of 28 healthy subjects. Results In whole-brain analyses, higher neuroticism among adults with depression was associated with increased activity in and connectivity with the right anterior insula cortex to incongruent compared with congruent emotional stimuli (all k ≥ 281, all p < .05 familywise error corrected), covarying for concurrent psychiatric distress. We also observed an unanticipated relationship between neuroticism and reduced activity in the precuneus (k = 269, p < .05 familywise error corrected). Exploratory analyses including healthy subjects suggested that associations between neuroticism and brain function may be nonlinear over the full range of neuroticism scores. Conclusions This study provides convergent evidence for the importance of the right anterior insula cortex as a brain-based marker of clinically meaningful individual differences in neuroticism among adults with depression. This is a critical next step in linking personality dysfunction, a replicated clinical predictor of differential antidepressant treatment response, with differences in underlying brain function.

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