Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depression

Jessica A. Cooper (), Makiah R. Nuutinen, Victoria M. Lawlor, Brittany A. M. DeVries, Elyssa M. Barrick, Shabnam Hossein, Daniel J. Cole, Chelsea V. Leonard, Evan C. Hahn, Andrew P. Teer, Grant S. Shields, George M. Slavich, Dost Ongur, J. Eric Jensen, Fei Du, Diego A. Pizzagalli and Michael T. Treadway ()
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Jessica A. Cooper: Emory University
Makiah R. Nuutinen: Emory University
Victoria M. Lawlor: Emory University
Brittany A. M. DeVries: Emory University
Elyssa M. Barrick: McLean Hospital/Harvard Medical School
Shabnam Hossein: Emory University
Daniel J. Cole: Emory University
Chelsea V. Leonard: Emory University
Evan C. Hahn: Emory University
Andrew P. Teer: Emory University
Grant S. Shields: University of Arkansas
George M. Slavich: University of California
Dost Ongur: McLean Hospital/Harvard Medical School
J. Eric Jensen: McLean Hospital/Harvard Medical School
Fei Du: McLean Hospital/Harvard Medical School
Diego A. Pizzagalli: McLean Hospital/Harvard Medical School
Michael T. Treadway: Emory University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Stress is a significant risk factor for the development of major depressive disorder (MDD), yet the underlying mechanisms remain unclear. Preclinically, adaptive and maladaptive stress-induced changes in glutamatergic function have been observed in the medial prefrontal cortex (mPFC). Here, we examine stress-induced changes in human mPFC glutamate using magnetic resonance spectroscopy (MRS) in two healthy control samples and a third sample of unmedicated participants with MDD who completed the Maastricht acute stress task, and one sample of healthy control participants who completed a no-stress control manipulation. In healthy controls, we find that the magnitude of mPFC glutamate response to the acute stressor decreases as individual levels of perceived stress increase. This adaptative glutamate response is absent in individuals with MDD and is associated with pessimistic expectations during a 1-month follow-up period. Together, this work shows evidence for glutamatergic adaptation to stress that is significantly disrupted in MDD.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23284-9

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DOI: 10.1038/s41467-021-23284-9

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