Effect of acute stress on PET studies

Participation in a nuclear imaging study is not something that people are used to, causing psychological stress and anxiety. Administration of PET radioligand usually requires intravenous cannulation, and arterial cannulation is often needed for blood sampling. The subjects need to be immobilized during imaging; restraint stress is commonly used in animals for studying stress response and activation of hypothalamic-pituitary-adrenal (HPA) axis. In diagnostic PET studies the disease or fear of suspected disease is an additional stressor.

Validation of PET radioligands for studying a certain phenomenon involves testing the repeatability of the method, usually in test-retest setting. Bias between test and retest PET scans is sometimes observed. After technical issues and diurnal variation are ruled out, acute stress can be plausible explanation, affecting the first scan more than the second scan, during which the study subject is already familiar with the procedure. Examples of such radiotracers include serotonin transporter radioligand [11C]DASB (Kim et al., 2006), glutamate receptor mGluR5 radioligand [18F]FPEB (Leurquin-Sterk et al., 2016), and SV2A radioligand [11C]UCB-J (Tuncel et al., 2020).

In studies of kidneys stress should be avoided. Middlekauff et al (1997) reported that induced mental stress reduced cortical renal blood flow by ∼30%. Gastrointestinal tract may also be affected by acute stress.

PET studies of stress and anxiety

[18F]FDG PET has been used to study neuronal activity and brain regions related to the HPA axis response (Kern et al., 2008; Hu et al., 2010; Wei et al., 2018; Luft et al., 2019).

The endocannabinoid system and especially CB1 receptors have an important role in stress and anxiety. From the psychoactive constituents of cannabis, cannabidiol has anxiolytic effects, and delta-9-THC can induce acute anxiety. CB1R PET radioligands have been used to study the effect of cannabinoids an anxiety (Bhattacharyya et al., 2017).

The effect of psychosocial stress on dopaminergic function has been studied using 6-[18F]-L-DOPA (Bloomfield et al., 2019). PET study has shown that dopamine and serotonin transporters are involved in social anxiety disorder (Hjorth et al., 2020). Acute stress is characterized by elevation of circulating cortisol, and cortisol promotes synthesis of serotonin transporter (Tafet et al., 2001).

Glucocorticoid receptor (GCR) and glucocorticoid levels in CNS may be involved in HPA axis responses. Intracellular enzyme 11β-HSD1, which converts inactive cortisone to active cortisol, can be assessed in vivo in human brain. GCR-targeting PET radioligands have shown promising results in animal studies.


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Literature

Chaouloff F. Serotonin, stress and corticoids. J Psychopharmacol. 2000; 14(2): 139-151. doi: 10.1177/026988110001400203.

Russell G, Lightman S. The human stress response. Nat Rev. 2019; 15: 525-534. doi: 10.1038/s41574-019-0228-0.



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Updated at: 2023-02-22
Created at: 2020-12-10
Written by: Vesa Oikonen