The amygdala on alert: A neuroimaging investigation into amygdala function during acute stress and its aftermath

Item does not contain fulltextRadboud Universiteit Nijmegen, 19 september 2011Promotor : Fernandez, G.S.E. Co-promotor : Hermans, E.J.183 p

The role of borderline personality disorder symptoms on absenteeism & work performance in the Netherlands Study of Depression and Anxiety (NESDA)

Background Symptoms of borderline personality disorder (BPD) were previously found to be associated with decreased work performance, even after controlling for depressive and anxiety disorders. Furthermore, co-occurrence of BPD and affective disorders is common. Therefore, we examined the effect of BPD symptoms on occupational functioning in workers with affective disorders. Methods Healthy workers (n = 287), workers with current depression/anxiety only (n = 195), workers with BPD symptoms only (n = 54), and workers with both depression/anxiety and BPD symptoms (n = 103) were selected from the Netherlands Study of Depression and Anxiety (NESDA). Both a categorical and dimensional approach were used to cross-sectionally study the effect of BPD symptoms on work performance and absenteeism. Results Compared to healthy controls, all symptomatic groups had impaired occupational functioning. Workers with current depression/anxiety had higher long-term absenteeism (OR = 3.59; 95%CI:1.83–7.02) and impaired work performance (OR = 7.81; 95%CI:4.44–13.73), workers with BPD symptoms only had higher impaired work performance (OR = 6.02 95%CI:2.76–13.09), and workers with both depression/anxiety and BPD symptoms had higher long-term absenteeism (OR = 3.66 95%CI:1.69–7.91) and impaired work performance (OR = 10.41 95%CI:5.38–20.15). No difference was found between the (symptomatic) groups. In the dimensional analysis, all associations between BPD symptoms and occupational measures disappeared when depressive symptoms were added. Depressive and BPD symptoms were highly correlated (r = .67). Conclusions Our findings confirm that both affective disorders and BPD symptoms are associated with occupational dysfunction. The effect of BPD symptoms however, seems mediated by depressive symptoms. This would suggest that focusing on affective symptoms in occupational health may be effective to improve occupational functioning in persons with BPD

No effects of psychosocial stress on intertemporal choice

Intertemporal choices - involving decisions which trade off instant and delayed outcomes - are often made under stress. It remains unknown, however, whether and how stress affects intertemporal choice. We subjected 142 healthy male subjects to a laboratory stress or control protocol, and asked them to make a series of intertemporal choices either directly after stress, or 20 minutes later (resulting in four experimental groups). Based on theory and evidence from behavioral economics and cellular neuroscience, we predicted a bidirectional effect of stress on intertemporal choice, with increases in impatience or present bias immediately after stress, but decreases in present bias or impatience when subjects are tested 20 minutes later. However, our results show no effects of stress on intertemporal choice at either time point, and individual differences in stress reactivity (changes in stress hormone levels over time) are not related to individual differences in intertemporal choice. Together, we did not find support for the hypothesis that psychosocial laboratory stressors affect intertemporal choice

Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum

Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MR-blockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol

Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders