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
Horst, J. ter; Kloet, E.R. de; Schachinger, H.; Oitzl, M.S. 2012
There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male... Show moreThere are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders. 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
Een emotionele gebeurtenis zoals een auto-ongeluk of eerste kus wordt goed onthouden. Stresshormonen spelen een grote rol bij deze link tussen emotie en cognitie. Onder normale omstandigheden... Show moreEen emotionele gebeurtenis zoals een auto-ongeluk of eerste kus wordt goed onthouden. Stresshormonen spelen een grote rol bij deze link tussen emotie en cognitie. Onder normale omstandigheden worden emotionele en cognitieve processen bevorderd door stresshormonen zoals adrenaline en corticostero_den. Echter, te veel of juist te weinig stresshormonen, of een te lange periode van stress kan emotie en cognitie zo be_nvloeden dat sommige mensen stressgerelateerde ziekten zoals posttraumatische stressstoornis (PTSS) ontwikkelen. Waarom de een wel en de ander niet ziek wordt van stress is niet bekend. Men denkt dat de corticostero_den hiervoor van belang zijn. Vera Brinks richtte zich in haar onderzoek op de rol van corticostero_den in de integratie van emotionele en cognitieve processen, en dus stressgerelateerde fysiologie en psychopathologie. De focus lag hierbij op de rol van de corticostero_d receptoren in de hersenen; de mineralo- (MR) en glucocortico_d receptoren (GR). Dit onderzoek verrichte zij bij muizen. De experimenten lieten zien dat emotie een flinke verbetering van cognitieve prestaties gaf bij de muizen. Hierbij bleek dat activering van de GR - in vergelijking met MR activatie - belangrijk is in de integratie van emotie en cognitie. GR activatie met hoeveelheden van het stress hormoon corticosteron die ook vrij komen bij milde stress, resulteert in een optimale prestatie wanneer het dier ook een emotionele ervaring had. Een te lage of te hoge activatie van deze receptor (de GR) verstoorde de integratie van emotie en cognitie. Die GR werkt dus optimaal binnen nauwe grenzen. Wanneer de MR genetisch wordt 'uitgeschakeld'(knockout), dan worden bepaalde negatieve ervaringen niet uitgedoofd (vergeten). Een belangrijke vinding was ook dat corticostero_dbehandeling de herinnering aan een traumatische gebeurtenis zowel kan verminderen als verbeteren afhankelijk van de genetische achtergrond van de muizen Deze kennis kan gebruikt worden bij de behandeling van het veel te sterke geheugen voor traumatische en angstige PTSS-pati_nten. Bovendien is het een basis om de genetische factoren te onderzoeken die bij kunnen dragen aan het ontstaan en de vermindering van het sterke angstgeheugen bij PTSS-pati_nten. Onze experimenten hebben laten zien dat de MR een uitstekende kandidaat is als target voor een geheel nieuw soort geneesmiddelen. Show less
