The locus coeruleus, a small brainstem nucleus, is the main source of the chemical norepineprine in the brain and is involved in a number of cognitive functions as well as several neurological and... Show moreThe locus coeruleus, a small brainstem nucleus, is the main source of the chemical norepineprine in the brain and is involved in a number of cognitive functions as well as several neurological and psychiatric disorders. In this dissertation we study the human LC-NE system, the anatomy of this tiny brainstem nucleus and the involvement of the LC-NE system in stress, arousal, cognitive flexibility and physiology (hormones & pupil responses). To date, the LC-NE system has been studied in animals or ex vivo (dead donors). This dissertation is among the first ones to study and visualize the LC-NE system in humans in vivo (alive volunteers) and to approach the human cognition and the study of the LC-NE system in a holistic manner: from central neuromodulators to hormones that are secreted in the body, from anatomy to physiology and cognition. To this end, all chapters were written by taking into consideration theoretical knowledge about the LC-NE system with regard to brain anatomy, cognitive functions, neuromodulation, physiological responses, and clinical applications. Chapters 2 and 3 deal mainly with the anatomy of the LC, while Chapters 4, 5 and 6 concentrate on cognition and human physiology. Additionally Chapters 5 and 6 take also a clinical approach. Show less
It is common in life to not perform at the very top of our cognitive abilities. This phenomenon usually exacerbates when we are under high levels of stress and in people with psychiatric disorders.... Show moreIt is common in life to not perform at the very top of our cognitive abilities. This phenomenon usually exacerbates when we are under high levels of stress and in people with psychiatric disorders. Attention to negative information is considered to play a crucial role in the development and maintenance of these disorders, especially anxiety-related disorders. Attention to negative information is not necessarily bad as it is an evolutionary function to protect us from dangerous situations. However, it can be destructive when it occurs constantly or when we need to focus on an important task. There are many situations where we have to perform difficult cognitive tasks and we worry about our performance or other people’s evaluation. Trait cognitive control, the ability to control attention and maintain a goal-relevant behaviour, is suggested to play a key role in the relationships between anxiety/stress, attention to negative information, and cognitive performance. Yet, the evidence is limited and further investigation is needed. In the current thesis, the relations between anxiety/stress, attention to emotional information, and cognitive performance will be investigated in a multidisciplinary approach, synthesizing clinical and cognitive factors and neurobiological underpinnings, while focusing on the role of trait cognitive control. Show less
The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are... Show moreThe forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent’s acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as ‘depressed’. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the FST is still increasing and that the majority of researchers qualifies the rodent’s floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback. Show less
With this thesis the PhD-candidate aims to enrich the body of evidence concerning the relation between stress and health, and the mediating role of (un)conscious perseverative cognitions (which is... Show moreWith this thesis the PhD-candidate aims to enrich the body of evidence concerning the relation between stress and health, and the mediating role of (un)conscious perseverative cognitions (which is captured in the extended perseverative cognition hypothesis). The main aim of this thesis was to find direct evidence for the extended PC hypothesis in real life. She examined whether reducing (un)conscious perseverative cognitions, or worry, improved stress-related physiological activity and subjective health complaints. Show less
Self‐esteem moderates the relationship between stress and (cardiovascular) health, with low self‐ esteem potentially exacerbating the impact of stressors. Boosting self‐esteem may therefore help to... Show moreSelf‐esteem moderates the relationship between stress and (cardiovascular) health, with low self‐ esteem potentially exacerbating the impact of stressors. Boosting self‐esteem may therefore help to buffer against stress. Subliminal evaluative conditioning (SEC), which subliminally couples self‐ words with positive words, has previously been successfully used to boost self‐esteem, but the existing studies are in need of replication. In this article, we aimed to replicate and extend previous SEC studies. The first 2 experiments simultaneously examined whether SEC increased self‐ esteem (Experiment 1, n = 84) and reduced cardiovascular reactivity to a stressor in high worriers (Experiment 2, n = 77). On the basis of these results, the 3rd experiment was set up to examine whether an adjusted personalized SEC task increased self‐esteem and reduced cardiac activity in high worriers (n = 81). Across the 3 experiments, no effects were found of SEC on implicit or explicit self‐esteem or affect or on cardiovascular (re)activity compared to a control condition in which the self was coupled with neutral words. The results do not support the use of the subliminal intervention in its current format. As stress is highly prevalent, future studies should focus on developing other cost‐effective and evidence‐based interventions. Show less
Stoffels, M.; Nijs, M.; Spinhoven, P.; Mesbah, R.; Hagenaars, M.A. 2017
Previous research has provided evidence for the link between psychological processes and psychophysiological health outcomes. Psychological interventions, such as face-to-face or online cognitive... Show morePrevious research has provided evidence for the link between psychological processes and psychophysiological health outcomes. Psychological interventions, such as face-to-face or online cognitive behavioral therapy (CBT) and serious games aimed at improving health, have shown promising results in promoting health outcomes. Few studies so far, however, have examined whether Internet-based CBT combined with serious gaming elements is effective in modulating health outcomes. Moreover, studies often did not incorporate psychophysiological or immunological challenges in order to gain insight into physiological responses to real-life challenges after psychological interventions. The overall aim of this study is to investigate the effects of a psychological intervention on self-reported and physiological health outcomes in response to immune and psychophysiological challenges. Show less
The aim of this thesis was to identify the neural mechanisms that enable a person to adaptively respond to, and recover from stress, which was studied in healthy controls, in people with increased... Show moreThe aim of this thesis was to identify the neural mechanisms that enable a person to adaptively respond to, and recover from stress, which was studied in healthy controls, in people with increased vulnerability or resilience to stress-related disorders, and in people with depression or PTSD, using magnetic resonance imaging (MRI). In most of the studies, a specific MRI method was employed, with which it is possible to assess how different brain regions communicate with each other (i.e., functional connectivity) when the brain is initiating or regulating stress responses. Structure, activity, and connectivity of the amygdala, a small brain region important for stress reactivity, was of main interest. The results show how stress influences information processing, and causes changes in the communication between brain areas, even long after the stressful event ended. Furthermore, personality dimensions associated with increased vulnerability or resilience to affective disorders were associated with changes in brain networks involved in emotion processing and regulation. Finally, smaller amygdala volumes were found in women with PTSD, while reduced integrity of affective brain networks was demonstrated in depression. Together, these results open important new avenues for future research into the short and long term effects of stress on the brain. Show less
Confidence in a theory increases when it is confirmed by relevant data. Alongside some consistent findings, the data in the prevailing thesis largely detail a lack of confirmation of the... Show moreConfidence in a theory increases when it is confirmed by relevant data. Alongside some consistent findings, the data in the prevailing thesis largely detail a lack of confirmation of the neurotrophin hypothesis. And where expected associations were established (e.g., abnormally low serum BDNF concentrations in the depressed state), the meaning often was not that clear (e.g., reverse causation). I therefore conclude, whilst taking limitations into account and acknowledging that the results are contingent upon imperfect and peripheral measurement, that the most reliable evidence in humans does not corroborate the neurotrophin hypothesis. So, given the data, the final words of this thesis are that solid work over novelty shows that the neurotrophin hypothesis should no longer be credited in its original form. All that glitters is not gold - back to the drawing table Show less
For a majority of people worries about upcoming stressful events are a common experience in daily life. The aim of this thesis was to examine the effects of common worries on somatic health. In... Show moreFor a majority of people worries about upcoming stressful events are a common experience in daily life. The aim of this thesis was to examine the effects of common worries on somatic health. In particular, the effects of worry on somatic health complaints, like headache and back pain, and on cardiac activity after stressful events were tested. Furthermore, the mechanisms by which worry was hypothesized to affect somatic health were investigated. The studies in this thesis add to the accumulating number of studies testing the perseverative cognition hypothesis stating that only perseverative cognitive representations of stressful events (worries) lead to prolonged stress-related physiological activity which, in turn, can lead to somatic disease. Taken together, the studies reported in this thesis provide evidence for the perseverative cognition hypothesis, that is, worry predicted adverse somatic health outcomes. In addition, the results of the studies presented in the second part of this thesis yielded several new and more specific hypotheses concerning the mechanisms behind the health effects of worry and the effects of worry on stress management therapies. All in all, evidence from real life and laboratory studies makes clear that worry might play a substantial role in somatic health. Show less
The main goal of the present thesis was to study the effects of stress and stress hormones on the retrieval of emotional memories in healthy humans. In addition, we were interested in the effects... Show moreThe main goal of the present thesis was to study the effects of stress and stress hormones on the retrieval of emotional memories in healthy humans. In addition, we were interested in the effects of stress hormones on post-retrieval processes like reconsolidation. That is, are there only acute and temporary effects of stress hormones on memory retrieval, or are there also long-term effects? Studying effects of stress hormones can be done in two ways; either by (experimentally) inducing stress in humans, or by exogenously administering doses of stress hormones. In the present thesis both ways were used. Furthermore, when investigating emotional memories, we can make use of memories that are created in a laboratory setting or those that derive from real life experiences, i.e. autobiographical memories. Again, both methods were investigated. We found acute stress and a single cortisol administration to have direct and long-term impairing effects on memory for neutral and emotional information that was learned and reactivated in a controlled laboratory situation. Future studies should shed more light on the generalizability of these findings to real life settings and clinical practice. Show less
De relatie tussen psychosociale stress en hart- en vaatziekten is intensief onderzocht. In de afgelopen decennia was het ‘reactivity model’ het belangrijkste theoretische uitgangspunt in de meeste... Show moreDe relatie tussen psychosociale stress en hart- en vaatziekten is intensief onderzocht. In de afgelopen decennia was het ‘reactivity model’ het belangrijkste theoretische uitgangspunt in de meeste onderzoeken. In dit model wordt verondersteld dat een heftige reactie van hart- en vaatstelsel tijdens stress een risicofactor zou zijn voor het ontwikkelen van hart- en vaatziekten. Hoewel het ‘reactivity model’ in het dieronderzoek veelbelovende resultaten boekte, ondervond vanwege resultaten uit humaan onderzoek een aantal fundamentele kritieken. Het brandpunt ligt bij momenten waarop een stressvolle gebeurtenis plaatsvindt, terwijl de periode daarvoor of daarna over het hoofd wordt gezien. Stressoren zijn gewoonlijk kort van duur en doen zich bij de meeste mensen niet frequent genoeg voor om consequenties voor de gezondheid te hebben. Deze factoren kunnen dus niet verklaren waarom chronische veranderingen in de balans van het hart- en vaatsysteem optreden. Een alternatief model dat wij voorstellen in dit proefschrift - het ‘prolonged activation model’- gaat er vanuit dat stressoren alleen kunnen leiden tot hart- en vaatziekten als ze in staat zijn verlengde fysiologische effecten te veroorzaken. Daarnaast is het onduidelijk waarom sommige stressoren wel verlengde effecten tot gevolg hebben en anderen niet. Tot nu toe verklaart het ‘perseverative cognition model’, als enige waarom sommige stressoren leiden tot verlengde effecten en anderen niet. Perseveratieve cognitie is het voortdurend denken aan negatieve gebeurtenissen en omvat fenomenen zoals piekeren of zich zorgen maken. Perseveratieve cognitie zorgt voor het ‘vers’ houden van het mentale beeld van een stressor alsmede de negatieve fysiologische effecten ervan, of deze stressor nu wel of niet plaatsvindt. Daarom bestaat een groot deel van dit proefschrift uit onderzoek naar de effecten van perseveratieve cognitie op hartactiviteit. We concluderen dat de resultaten van dit proefschrift aangeven dat perseveratieve cognitie, een belangrijke factor is in het ‘prolonged activation model’. Het verklaart niet alle verlengde effecten van stressoren, maar heeft daarentegen zelf een verlengd fysiologisch effect, dat zelfs langer lijkt dan dat van stressoren. Deze vondst en de effecten van 'piekergeneigdheid' op hartactiviteit gedurende de slaap suggereren dat onderzoek in de toekomst gericht zou moeten worden op de rol van onbewuste perseveratieve cognitie. Show less
