Effects of mineralocorticoid-receptor stimulation on risk taking behavior in young healthy men and women
Introduction
Stress, conceptualized as a threat to the physiological and psychological integrity of the organism, requires specific cognitive and behavioral adjustments. Situational affordances demand quick action to counter the threat and cope with the stressor(McEwen, 1998). For instance, acute stress has been shown to induce a shift from deliberate, goal-directed behavior towards habitual and intuitive behavior (Schwabe and Wolf, 2011), a shift that is reflected in the activation of different information processing systems (Margittai et al., 2015). Risk taking behavior as a process affected by stress has only recently received research attention. In general, exposure to an acute stressful situation increases the tendency for risk taking (Morgado et al., 2015, Starcke and Brand, 2012). However, experimental results regarding stress effects on risk taking are equivocal and affected by personality characteristics such as impulsivity and sensation seeking (Lejuez et al., 2002, Wise et al., 2014). Some studies report divergent effects for men and women (Lighthall et al., 2009, Lighthall et al., 2012, van den Bos et al., 2009) or gains and losses (Buckert et al., 2014, Pabst et al., 2013b, Porcelli and Delgado, 2009), with other studies finding no effects of stress at all (Haushofer et al., 2013).
Comparatively little research has been devoted to the underlying neuroendocrine mechanisms of stress effects on risk taking behavior. Following the short-lived activation of the catecholaminergic stress system, the glucocorticoid cortisol is secreted from the adrenals and becomes centrally active by crossing the blood-brain barrier. These two stress systems are the main physiological mechanisms for behavioral effects of stress. In an early study, van Honk et al. (2003) reported an influence of basal cortisol levels on punishment sensitivity and reward dependency in a risk taking task, with more disadvantageous choices for participants with low cortisol levels. Another study (Chumbley et al., 2014) that investigated basal cortisol levels (derived from hair samples) found a positive relationship between endogenous cortisol levels and aversion for losses. Pabst et al. (2013a) reported decreased risk taking when the decision task was performed 5 or 18 min after a psychosocial stressor – but an increase in a 28 min delay. This result was explained by the authors with differential effects of rapidly-acting catecholamines and delayed effects of cortisol. In a direct pharmacological design, the administration of exogenous cortisol (hydrocortisone) increased risky decision making in male participants (Putman et al., 2010). These findings support the role of the cortisol system in the stress-induced modulation of risk taking.
Cortisol can easily cross the blood–brain barrier and feeds back on the brain via two different receptor types: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), with the MR occurring both in the cell nucleus and the membrane. Unlike the permanently occupied nuclear MR, the membrane-bound MR plays an active role in the acute stress response (Vogel et al., 2016). While cortisol effects on the brain have traditionally been attributed to the activation of the GR complex, recent studies could demonstrate the significance of the MR for various psychological domains (de Kloet, 2014, Groeneweg et al., 2011, Ter Horst et al., 2012), with both receptor types promoting differential, and to some degree opposing functional processes (Hermans et al., 2014, Vogel et al., 2016). Activation of the MR can improve executive functions and memory performance (Hinkelmann et al., 2014, Otte et al., 2015, Schultebraucks et al., 2016a), while blockade of the MR impaired these processes (Cornelisse et al., 2011, Otte et al., 2007, Rimmele et al., 2013). Furthermore, the MR seems to be specifically involved in emotional processing and the appraisal of novel situations; these are functions that rely on anatomical structures such as the amygdala and the prefrontal cortex, that also underlie reward processing, outcome prediction and risk assessment (Gathmann et al., 2014, Maier et al., 2015, Porcelli et al., 2012). Accordingly, the stress induced shift towards a cognitively less demanding amygdala-based learning strategy is mediated by MR activation (Vogel et al., 2015). Specific MR haplotypes are linked to dispositional optimism (Klok et al., 2011), which can be conceived as high expectations regarding future outcomes (Carver and Scheier, 2014). Recent studies in rats that investigated time-dependent effects of corticosterone (the cortisol equivalent in rodents) on reward-based decision-making imply differential effects for MR- and GR-mediated processes (Koot et al., 2013, Koot et al., 2014).
These receptor-specific effects cannot be differentially assessed by hydrocortisone administration because hydrocortisone acts on both MR and GR. In this study we examined the specific effects of MR stimulation on risk taking. To this end, we administered fludrocortisone, a selective MR agonist, to healthy young men and women in a placebo controlled, double-blind, full-factorial design. Risk taking was assessed with the Balloon Analogue Risk Task (BART), an established measure of risk taking behavior that has previously been applied to investigate stress effects on risk taking (Lighthall et al., 2009, Lighthall et al., 2012, Mehta et al., 2015; Reynolds et al., 2013). Since previous studies could demonstrate sex differences in risk taking behavior, we included sex as a factor in our analysis.
We hypothesized that participants in the fludrocortisone condition would show increased risk taking when compared to participants in the placebo condition. Based on the generally stronger risk tolerance in men (Byrnes et al., 1999), we expected men to exhibit riskier decision making compared to women. Since conflicting results have been reported regarding sex specific effects of stress on risk taking (Starcke and Brand, 2012), our study remains exploratory with regard to an interaction between sex and our drug intervention.
Section snippets
Participants
In total, 80 (40 women, age 18–30 years, mean age = 23.9 ± 3.3) healthy participants completed the study. Participants were undergraduate students, recruited at the Humboldt University and Free University Berlin. They received a monetary compensation of 40€.
The sex ratio was balanced for each condition. One male participant had to be excluded because of technical difficulties.
Exclusion criteria were any neurological, psychiatric or psychological disorders, acute or persistent medical disease and
Demographic data
Participants in the treatment conditions (fludrocortisone vs. placebo) did not differ with regard to age, sex, BMI, smoking or hormonal contraception (see Table 1).
Questionnaire data
There was no significant difference between treatment groups for any of the three dimensions of the MDBF, the DOSPERT or the DMI-45 (p > 0.05) (see Table 2).
Salivary cortisol responses
We found a significant treatment × time interaction (F 4,284 = 9.71, p <0.001; ηp2 = 0.12). Post-hoc t-tests revealed a significant difference between treatment groups for the measurement
Discussion
In the current study, we investigated the effect of MR-receptor stimulation by fludrocortisone on risk taking behavior. Consistent with our hypothesis, we found increased risk taking in the fludrocortisone group, as compared to placebo. This finding is in line with the large number of previous studies that have investigated stress effects or effects of exogenous cortisol on risk taking (Morgado et al., 2015, Starcke and Brand, 2012). Riskier decision making after administration of exogenous
Conflict of interest
Christian Otte has received honoraria fees for lectures from Lundbeck and Servier and has received compensation as a member of the scientific advisory board from Lundbeck. Christian Eric Deuter, Katja Wingenfeld, Katharina Schultebrauks, Julian Hellmann-Regen, Dominique Piber report no conflict of interest.
Funding
No external funding.
Disclosure
Christian Otte has received honoraria fees for lectures from Lundbeck and Servier and has received compensation as a member of the scientific advisory board from Lundbeck. Christian Eric Deuter, Katja Wingenfeld, Katharina Schultebrauks, Julian Hellmann-Regen, Dominique Piber report no conflict of interest.
Contributors
Christian Eric Deuter: Statistical analysis, literature research, wrote the manuscript.
Katharina Schultebrauks: Data collection, statistical analysis, data management, recruitment of participants.
Katja Wingenfeld: Co-PI, study design, supervising statistics, literature research, supervising the manuscript.
Dominique Piber: Data collection, statistical analysis, data management, recruitment of participants.
Julian Hellmann-Regen: Analysis and interpretation of cortisol data.
Christian Otte: PI,
Acknowledgement
We would like to thank all participants who took part in this study.
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