Heightened SAM- and HPA-axis activity during acute stress impairs decision-making: A systematic review on underlying neuropharmacological mechanisms

Abstract

Individuals might be exposed to intense acute stress while having to make decisions with far-reaching consequences. Acute stress impairs processes required for decision-making by activating different biological stress cascades that in turn affect the brain. By knowing which stress system, brain areas, and receptors are responsible for compromised decision-making processes, we can effectively find potential pharmaceutics that can prevent the deteriorating effects of acute stress. We used a systematic review procedure and found 44 articles providing information on this topic. Decision-making processes could be subdivided into 4 domains (cognitive, motivational, affective, and predictability) and could be referenced to specific brain areas, while mostly being impaired by molecules associated with the sympathetic-adrenal-medullar and hypothalamic-pituitary-adrenal axes. Potential drugs to alleviate these effects included α₁ and β adrenoceptor antagonists, α₂ adrenoceptor agonists, and corticotropin releasing factor receptor_1/2 antagonists, while consistent stress-like effects were found with yohimbine, an α₂ adrenoceptor antagonist. We suggest possible avenues for future research.

Keywords: Acute stress; Cognition; Decision-making; HPA; Neuromodulation; SAM.

Fig. 1

The PRISMA flowchart of the research article selection process.

Fig. 2

An overview of all articles that utilized an acute stressor in their experimental design. A distinction was made between studies that investigated SAM axis (orange) or HPA axis (cyan) related phenomena. Effects of acute stress could either enhance, impair or do both on decision-making related processes. Decision-making processes are further categorized in four domains: cognitive (blue; n = 17), motivational (red; n = 20), affective (purple; n = 4), and predictability (green; n = 7). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Frequencies of brain areas that were involved in decision-making processes, subdivided into the 4 decision-making domains. Frontal cortex (n = 20), amygdala (n = 6), striatum (n = 7), brainstem (n = 13), midbrain (n = 2), and other brain areas (n = 5).

Fig. 4

Brain areas in the human (top) and rodent (bottom) brain that appear to be involved in decision-making processes and may be affected by the effects of acute stress. Brains are sliced on the midsagittal axis, displaying inner and outer areas. As colour coded in Fig. 2, four domains of decision-making were associated with different brain areas: OFC (rodent n = 3); mOFC (human n = 1); PFC (rodent n = 1); mPFC (rodent n = 3); dlPFC (human n = 3); dmPFC (human n = 1, rodent n = 1); vHC (rodent n = 1); ventral striatum (human n = 1); NAcc (human n = 2, rodent n = 2); dorsal striatum (human n = 2); CN (human n = 1); ACC (human n = 2, rodent n = 2); parietal cortex (human n = 1); TPJ (human n = 1); IPL (human n = 1); insula (human n = 2); amygdala (rodent n = 3); BLA (rodent n = 1); SFA (human n = 1); CeA (rodent n = 1); VTA (rodent n = 1); LC (human n = 2, rodent n = 4); DRN (rodent n = 1). Involvement of SAM and/or HPA activity during acute stress is indicated in respective brain areas. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)