The effects of psychosocial stress on dopaminergic function and the acute stress response.

Michael Ap Bloomfield,Oliver Howes,Tom P Freeman,Robert A Mccutcheon,Matthew Kempton

doi:10.7554/elife.46797

Michael Ap Bloomfield, Oliver Howes + Show 3 more

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https://doi.org/10.7554/elife.46797

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Abstract

Chronic psychosocial adversity induces vulnerability to mental illnesses. Animal studies demonstrate that this may be mediated by dopaminergic dysfunction. We therefore investigated whether long-term exposure to psychosocial adversity was associated with dopamine dysfunction and its relationship to psychological and physiological responses to acute stress. Using 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F]-DOPA) positron emission tomography (PET), we compared dopamine synthesis capacity in n = 17 human participants with high cumulative exposure to psychosocial adversity with n = 17 age- and sex-matched participants with low cumulative exposure. The PET scan took place 2 hr after the induction of acute psychosocial stress using the Montréal Imaging Stress Task to induce acute psychosocial stress. We found that dopamine synthesis correlated with subjective threat and physiological response to acute psychosocial stress in the low exposure group. Long-term exposure to psychosocial adversity was associated with dampened striatal dopaminergic function (p=0.03, d = 0.80) and that psychosocial adversity blunted physiological yet potentiated subjective responses to acute psychosocial stress. Future studies should investigate the roles of these changes in vulnerability to mental illnesses.

Highlights

Chronic psychosocial adversity increases the risk of mental illnesses including schizophrenia and depression (van Os et al, 2010; Howes and Murray, 2014; Parker, 1983)
high adversity (HA) scored significantly higher than low adversity (LA) on subclinical measures of depressive symptoms (BDI), the degree to which previous stressors were having an impact on their lives in the week prior to scanning (BIE) and aberrant salience (ASI)
As we found that dopamine synthesis capacity is correlated with both subjective and physiological response to stress in LA, we performed a regression analysis to identify which subregion is the best predictor for the physiological measures

Summary

Introduction

Chronic psychosocial adversity increases the risk of mental illnesses including schizophrenia and depression (van Os et al, 2010; Howes and Murray, 2014; Parker, 1983). These adverse factors include developmental psychological trauma (Bendall et al, 2008) and adult life events (situations or occurrences that bring about a negative change in personal circumstances and involve threat) (Beards et al, 2013; Brown and Birley, 1968). We lack a precise mechanistic understanding of how exposure to these risk factors induces vulnerability to mental illness, and why these exposures all increase risk. One common component underlying these factors is exposure to psychosocial stress (Howes and Murray, 2014) via activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system as part of the normal biological stress response (Taylor, 2010)

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