Key result
The Maastricht Acute Stress Task induced changes in mPFC glutamate that were inversely correlated with recent perceived stress in healthy controls (rs = -0.457), an adaptive response that was absent in unmedicated individuals with major depressive disorder.
Why the study?
Stress is a major risk factor for mental illness such as MDD, but the biological mechanisms and adaptive versus maladaptive responses to repeated stress remain unclear.
Does an acute stressor alter mPFC glutamate levels differently in healthy controls compared to individuals with MDD?
Cross-Sectional (n=88)
Yes
Does an acute stressor alter mPFC glutamate levels differently in healthy controls compared to individuals with MDD?
Effect estimate: rs = -0.457
p-value: p=0.022
Glutamatergic adaptation to stress in the medial prefrontal cortex is present in healthy individuals but disrupted in unmedicated MDD, correlating with pessimistic beliefs.
Hypothesis-generating for mPFC glutamate changes after stress; prospective human studies needed before clinical translation.
Stress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.
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Cooper et al. (2020) conducted a cross-sectional in Major Depressive Disorder (n=88). Maastricht Acute Stress Task (MAST) vs. No-Stress Control (NSC) was evaluated on Correlation between recent perceived stress (PSS scores) and percent change in mPFC glutamate (%DGlu) following acute stress in healthy controls (rs = -0.457, p=0.022). The Maastricht Acute Stress Task induced changes in mPFC glutamate that were inversely correlated with recent perceived stress in healthy controls (rs = -0.457), an adaptive response that was absent in unmedicated individuals with major depressive disorder.
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