abstract: Chronic stress results in functional and structural changes to the hippocampus. Decades of research has led to insights into the mechanisms underlying the chronic stress-induced deficits in hippocampal-mediated cognition and reduction of dendritic complexity of hippocampal neurons. Recently, a considerable focus of chronic stress research has investigated the mechanisms behind the improvements in hippocampal mediated cognition when chronic stress ends and a post-stress rest period is given. Consequently, the goal of this dissertation is to uncover the mechanisms that allow for spatial ability to improve in the aftermath of chronic stress. In chapter 2, the protein brain derived neurotrophic factor (BDNF) was investigated as a mechanism that allows for spatial ability to show improvements following the end of chronic stress. It was found that decreasing the expression of BDNF in the hippocampus prevented spatial memory improvements following a post-stress rest period. Chapter 3 was performed to determine whether hippocampal CA3 apical dendritic complexity requires BDNF to show improvements following a post-stress rest period, and whether a receptor for BDNF, TrkB, mediates the improvements of spatial ability and dendritic complexity in a temporal manner, i.e. during the rest period only. These experiments showed that decreased hippocampal BDNF expression prevented improvements in dendritic complexity, and administration of a TrkB antagonist during the rest period also prevented the improvements in spatial ability and dendritic complexity. In chapter 4, the role of the GABAergic system on spatial ability following chronic stress and a post-stress rest period was investigated. Following chronic stress, it was found that male rats showed impairments on the acquisition phase of the RAWM and this correlated with limbic glutamic acid decarboxylase, a marker for GABA. In chapter 5, a transgenic mouse that expresses a permanent marker on all GABAergic interneurons was used to assess the effects of chronic stress and a post-stress rest period on hippocampal GABAergic neurons. While no changes were found on the total number of GABAergic interneurons, specific subtypes of GABAergic interneurons were affected by stressor manipulations. Collectively, these studies reveal some mechanisms behind the plasticity seen in the hippocampus in response to a post-stress rest period. / Dissertation/Thesis / Doctoral Dissertation Psychology 2018

abstract: Cognitive reappraisal, or redefining the meaning of a stressful circumstance, is useful in regulating emotional responses to acute stressors and may be mobilized to up- or down- regulate the stressors’ emotional salience. A conceptually-related but more targeted emotion regulation strategy to that offered by cognitive reappraisal, termed positive cognitive shift, was examined in the current study. Positive cognitive shift (“PCS”) is defined as a point of cognitive transformation during a chronic, stressful situation that alters the meaning and emotional salience of the situation for the individual. Key aspects of the PCS that differentiate it from the broader reappraisal construct are that it 1) is relevant to responses to chronic (versus acute) aversive events, 2) is deployed when there is a mismatch between coping and stressors, and 3) involves insight together with redefinition in meaning of the situation generating stress. The current study used qualitative and quantitative analyses to 1) examine whether PCS is an observable, reliable, and valid experience in response to a stressful event that occurred in the past year, and 2) test whether PCS moderates the relations between the number of past-year stressful life circumstances and subsequent emotional well-being and functional health. A community sample of 175 middle-aged individuals were interviewed regarded a past chronic stressor and completed questionnaires regarding number of past year stressors and health outcomes. Theory-based coding of interviews was conducted to derive reliable scores for PCS, and findings indicated that PCS was evident in 37.7 % of participant responses. Furthermore, PCS scores were related positively to openness, personal growth from one’s most difficult lifetime event, and affect intensity-calm, in line with predictions. Also in line with prediction, PCS moderated the relations between number of past-year life events and health outcomes, such that the deleterious relations between past year stressful events and cognitive functioning, wellbeing, positive affect, and negative affect were weaker among individuals higher versus lower in PCS. Of note, PCS moderation effects diminished as the number of stressful events increased. / Dissertation/Thesis / Doctoral Dissertation Psychology 2018

Submitted by ADRIANA BEATRIZ BARRETTO (adriana.barretto@gmail.com) on 2018-04-25T17:07:16Z No. of bitstreams: 1 Tese Definitiva.pdf: 1000337 bytes, checksum: aa40cdf128c269fcfa1393bb66b32c79 (MD5) / Approved for entry into archive by Sulamita Selma C Colnago null (sulamita@btu.unesp.br) on 2018-04-26T18:52:18Z (GMT) No. of bitstreams: 1 barreto_ab_dr_bot_int.pdf: 1000337 bytes, checksum: aa40cdf128c269fcfa1393bb66b32c79 (MD5) / Made available in DSpace on 2018-04-26T18:52:18Z (GMT). No. of bitstreams: 1 barreto_ab_dr_bot_int.pdf: 1000337 bytes, checksum: aa40cdf128c269fcfa1393bb66b32c79 (MD5) Previous issue date: 2018-03-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / CAPÍTULO 1 – Neste estudo avaliamos o efeito do estresse agudo e crônico na memória de aprendizagem de tilápias-do-Nilo com diferentes perfis de personalidade. Inicialmente definimos a personalidade dos peixes através de testes de objeto novo e exposição a um predador, classificando-os em shy (tímido) ou bold (ousado) e em seguida estes indivíduos foram condicionados por um método simples de condicionamento clássico como forma de aprendizagem para posterior avaliação da memória. Os peixes shy foram então divididos em dois grupos, sendo que em um deles os peixes foram diariamente estressados por hipóxia, perseguição com rede ou confinamento (grupo shy-experimental) por 64 dias consecutivos, enquanto que no outro grupo os peixes permaneceram apenas isolados (grupo shy-controle) pelo mesmo período de tempo. O mesmo procedimento foi adotado com os peixes classificados como bold. Nesse mesmo período, testes de memória foram realizados em dias específicos, tanto nos grupos experimental quanto nos grupos controle. Ao final do experimento, reavaliamos se as personalidades se mantiveram. Obtivemos que o estresse agudo afetou a memória de aprendizado em peixes, principalmente em indivíduos com perfil de personalidade shy. CAPÍTULO 2 – Aqui desenvolvemos uma metodologia simples de condicionamento clássico facilmente aplicável em laboratórios de experimentação com peixes, quando comparados aos métodos descritos na literatura atual, onde os estímulos geralmente aplicados para condicionamento (som ou luz) podem interferir nas respostas dos animais experimentais presentes no mesmo laboratório. Para tal condicionamento, isolamos os peixes em aquários individuais e introduzimos um jato de água em cada aquário (sem que os peixes pudessem perceber a presença do pesquisador) causando movimentação da água (estímulo condicionado) neste local específico do aquário. Em seguida, um pellet de ração (estímulo incondicionado) foi introduzido no mesmo local da movimentação da água (novamente sem que os peixes pudessem perceber a presença do pesquisador). Esses procedimentos foram realizados durante 20 dias seguidos, 4 vezes ao dia. Obtivemos que após 14 dias de condicionamento todos os peixes associaram estímulo condicionado e incondicionado, confirmando a efetividade deste método simples e sem interferência nos demais animais experimentais presentes no ambiente. / CHAPTER 1 - In this study we evaluated the effect of acute and chronic stress in learning memory of Nile tilapia with different personality profiles. Initially we defined the personality of the fish through the testo f new object and exposure to a predator, classifying them as shy or bold, and then these individuals were conditioned by a simple method of classical conditioning as a way of learning to evaluation of memory. The shy fish were divided into two groups, and in one group the fish were daily stressed by hypoxia, net chase or confinement (shy-experimental group) for 64 consecutive days, while in the other group the fish remained only isolated (shy-control group) for the same time period. The same procedure was adopted with fish classified as bold. During the same period, memory tests were performed on specific days, in both groups, experimental and control group. At the end of the experiment, we reevaluated whether the personalities held. We found that acute stress affected learning memory in fish, especially in individuals with shy personality profiles. CHAPTER 2 - Here we develop a classical conditioning methodology easily applicable in fish experimentation laboratories when compared to the methods described in the current literature, where the stimuli generally applied for conditioning (sound or light) can interfere with the responses of experimental animals present in the same laboratory. For this conditioning, we isolate the fish in individual aquariums and introduce a jet of water into each aquarium (without the fish could perceive the presence of the researcher) causing water movement (conditioned stimulus) in this specific aquarium site. Then a feed pellet (unconditioned stimulus) was introduced in the same place as the water movement (again without the fish being able to perceive the presence of the researcher). These procedures were performed for 20 consecutive days, 4 times daily. We obtained that after 14 days of conditioning all the fish associated conditioned and unconditioned stimulus, confirming the effectiveness of this simple method and without interference in the other experimental animals present in the environment.

abstract: Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the hippocampus with adeno- associated viral vectors containing the coding sequence for short interfering (si)RNA directed against BDNF or a scrambled sequence (Scr), with both containing the coding information for green fluorescent protein to aid in anatomical localization. Rats were then chronically restrained (wire mesh, 6h/d/21d) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trial. Rats in the Str-Imm group, regardless of viral vector contents, committed more errors in the spatial reference memory domain than did non-stressed controls. Importantly, the typical improvement in spatial memory following recovery from chronic stress was blocked with the siRNA against BDNF, as Str-Rec-siRNA performed worse on the RAWM compared to the non-stressed controls or Str-Rec-Scr. These effects were specific for the reference memory domain as repeated entry errors that reflect spatial working memory were unaffected by stress condition or viral vector contents. These results demonstrate that hippocampal BDNF is necessary for the recovery from stress-induced hippocampal dependent spatial memory deficits in the reference memory domain. / Dissertation/Thesis / M.A. Psychology 2013

abstract: The brain is a fundamental target of the stress response that promotes adaptation and survival but the repeated activation of the stress response has the potential alter cognition, emotion, and motivation, key functions of the limbic system. Three structures of the limbic system in particular, the hippocampus, medial prefrontal cortex (mPFC), and amygdala, are of special interest due to documented structural changes and their implication in post-traumatic stress disorder (PTSD). One of many notable chronic stress-induced changes include dendritic arbor restructuring, which reflect plasticity patterns in parallel with the direction of alterations observed in functional imaging studies in PTSD patients. For instance, chronic stress produces dendritic retraction in the hippocampus and mPFC, but dendritic hypertrophy in the amygdala, consistent with functional imaging in patients with PTSD. Some have hypothesized that these limbic region's modifications contribute to one's susceptibility to develop PTSD following a traumatic event. Consequently, we used a familiar chronic stress procedure in a rat model to create a vulnerable brain that might develop traits consistent with PTSD when presented with a challenge. In adult male rats, chronic stress by wire mesh restraint (6h/d/21d) was followed by a variety of behavioral tasks including radial arm water maze (RAWM), fear conditioning and extinction, and fear memory reconsolidation to determine chronic stress effects on behaviors mediated by these limbic structures. In chapter 2, we corroborated past findings that chronic stress caused hippocampal CA3 dendritic retraction. Importantly, we present new findings that CA3 dendritic retraction corresponded with poor spatial memory in the RAWM and that these outcomes reversed after a recovery period. In chapter 3, we also showed that chronic stress impaired mPFC-mediated extinction memory, findings that others have reported. Using carefully assessed behavior, we present new findings that chronic stress impacted nonassociative fear by enhancing contextual fear during extinction that generalized to a new context. Moreover, the generalization behavior corresponded with enhanced functional activation in the hippocampus and amygdala during fear extinction memory retrieval. In chapter 5, we showed for the first time that chronic stress enhanced amygdala functional activation during fear memory retrieval, i.e., reactivation. Moreover, these enhanced fear memories were resistant to protein synthesis interference to disrupt a previously formed memory, called reconsolidation in a novel attempt to weaken chronic stress enhanced traumatic memory. Collectively, these studies demonstrated the plastic and dynamic effects of chronic stress on limbic neurocircuitry implicated in PTSD. We showed that chronic stress created a structural and functional imbalance across the hippocampus, mPFC, and amygdala, which lead to a PTSD-like phenotype with persistent and exaggerated fear following fear conditioning. These behavioral disruptions in conjunction with morphological and functional imaging data reflect a chronic stress-induced imbalance between hippocampal and mPFC regulation in favor of amygdala function overdrive, and supports a novel approach for traumatic memory processing in PTSD. / Dissertation/Thesis / Ph.D. Psychology 2013

O estresse parece favorecer a hiperalgesia e alodinia, podendo estar associados à alteração da função muscular mastigatória. Alterações morfofisiológicas em músculos da mastigação induzidos pela alteração oclusal associado ao estresse crônico ainda são escassas na literatura. Este estudo investigou os efeitos do estresse crônico repetido em músculo masseter superficial e profundo de ratos submetidos ou não à exodontia unilateral no ganho do peso dos animais, nas alterações morfológicas (HE, MET), histoquímicas (NADH, SDH e ROS), imunoistoquímicas (laminina e CD31), atividade de MMP-2, -9 e infiltração de neutrófilos (MPO). Vinte ratos (machos, 200g) foram alocados em quatro grupos (n=5): controle (GC), exodontia unilateral (GM), estresse crônico repetido (GE), exodontia associado ao estresse crônico repetido (GME). GE e GME foram submetidos a 10 dias de protocolo de estresse crônico repetido (2 horas diárias) a partir do 14º dia após a exodontia. Houve uma diminuição significativa no ganho de peso dos animais GE e GME. Não foram observadas alterações nos níveis de MMPs e na infiltração de neutrófilos no feixe superficial dos diferentes grupos. GE, GM e GME demostraram alterações morfofisiológicas, ultraestruturais e histoquímicas no feixe profundo, com características específicas e distintas de GC; GE apresentou as maiores alterações. Conclui-se que a exodontia e sua associação ao estresse foram responsáveis por discretas alterações morfofisiológicas no músculo masseter de ratos, contudo o estresse crônico repetido causou modificações morfofisiológicas e ultraestruturais significantes, sendo responsável também pela alteração no peso dos animais. / Stress seems to favor the hyperalgesia and allodynia, which may be related with altered masticatory muscle function. Morphological and physiological changes in the masticatory muscles induced by occlusal alteration associated with chronic stress are still scarce in the literature. This study investigated the effects of repeated chronic stress in superficial and deep masseter muscle of rats with or without the extraction unilateral weight gain of animals and morphological changes (HE MET), histochemical (NADH, SDH and ROS), immunohistochemical (laminin and CD31), MMP-2, -9 activities and neutrophil infiltration (MPO). Twenty rats (male, 200g) were allocated into four groups (n=5): control group (CG), unilateral exodontia (MG), repeated chronic stress (EG), extodontia and repeated chronic stress (MEG). EG and MEG were submitted to 10 days of repeated chronic stress protocol, 2 hours daily, from the 14th day after the extraction. There was a significant decrease in weight gain of animals EG and MEG. No changes were observed in the levels of MMPs and neutrophil infiltration among different groups. EG, MG and MEG have shown morphophisyological, ultrastructural and histochemical changes with specific characteristics and distinct GC GE presenting the higher changes. We conclude that the exodontia and its association to stress were responsible for discrete morphophysiological changes in the masseter muscle of rats, however repeated chronic stress caused significant morphophysiological and ultrastructural changes, being also responsible for change in weight of the animals.

L'anthropisation croissante et les changements globaux entrainent de nombreuses perturbations dans l'environnement conduisant à la dégradation, et même à la destruction d'habitat. Le modèle allostatique proposé par McEwen et Wingfield en 2003 permet de mieux appréhender les relations entre physiologie et réponses démographique dans le cadre de la physiologie de la conservation. A travers des approches expérimentales en milieux controlé et semi-naturel nous avons testé l'effet de d'un stress chronique sur les changements des traits d'histoires de vie et les paramétres physiologique chez le lézard vivipare (Zootoca vivipara). Nous discutons de la caractérisation de la charge allostatique et des effets à court terme et long terme d'un stress chronique et l'utilisation de la charge allostatique comme indicateur de la dégradation de l'habitat. Ce travail pourra être utilisé afin de mieux comprendre et prédire la dynamique des populations naturelles soumises aux changements globaux. / Increasing anthropogenic and global changes are causing many disturbances in the environment leading to degradation and even destruction of habitat. The allostatic model proposed by McEwen and Wingfield in 2003 provides a better understanding of the relationships between physiology and demographic responses within the framework of conservation physiology. Experimental approaches in controlled and semi-natural environments have tested the effect of chronic stress on changes in life histories and physiological parameters in the viviparous lizard (Zootoca vivipara). We discuss the characterization of allostatic charge and the short-term and long-term effects of chronic stress and the use of allostatic charge as an indicator of habitat degradation. This work can be used to better understand and predict the dynamics of natural populations subjected to global changes.

Over the last 20 years, there has been increasing research on the negative effects of discrimination on the mental and physical health of people of color. As mental health has an important relationship with the functional connectivity of brain networks, it is vital to further understand this. One way to measure functional brain connectivity is by observing the activity of the brain’s resting state networks (RSN) while a participant is at rest. Previous studies investigating connectivity have demonstrated a relationship between altered connectivity of RSNs and neuropsychiatric disorders, including Alzheimer’s disease, depression, and anxiety. The RSN of interest in this analysis is the salience network (SN). This network, anchored in the anterior insula and dorsal anterior cingulate cortex, is involved in the responses to “salient” stimuli that are infrequent in space or time, compete for an individual’s attention, and are surprising or emotionally engaging, such as an act of discrimination. The aim of this study was to use a seed-based correlation analysis to examine the relationship between perceived discrimination and the functional connectivity of the SN in black and white participants and to evaluate the differences in SN functional connectivity between black and white participants. Resting state functional connectivity was measured by using the functional magnetic resonance imaging (fMRI) data collected from 18 healthy older adults partaking in two different studies investigating aging, cognition, and the accompanying changes in neuroanatomy. The Analysis of Functional NeuroImages (AFNI) software was used to examine the correlations in activation in the primary nodes of the SN with activation in clusters in the other primary nodes. Perceived discrimination was measured using the Experiences of Discrimination Scale (EOD), a self-report measuring the frequency of instances of discrimination and the perceived reason behind the discrimination. Preliminary results from this analysis demonstrated that black participants, when compared to the white participants, demonstrated greater functional connectivity between the left and right insula and decreased functional connectivity between the right anterior cingulate cortex and the right insula. Black participants demonstrated a positive association between perceived overall discrimination and functional connectivity between the right and left insula and a negative association between perceived overall discrimination and functional connectivity between the right anterior cingulate cortex and the left insula. The white participants demonstrated a negative association between perceived overall discrimination and functional connectivity between the left and the right insula. Considering the inability for these results to survive correction for multiple comparisons, a larger sample size is necessary to obtain true statistical significance. Although existing research has implicated functional connectivity changes in the regions of the salience network in populations experiencing social exclusion, anxiety, and depression, further analyses are necessary to expand the limited research available regarding the effects of overall and race-based discrimination on the resting state functional connectivity of neural networks involved in emotional processing.

Orientador: Percília Cardoso Giaquinto / Resumo: CAPÍTULO 1 – Neste estudo avaliamos o efeito do estresse agudo e crônico na memória de aprendizagem de tilápias-do-Nilo com diferentes perfis de personalidade. Inicialmente definimos a personalidade dos peixes através de testes de objeto novo e exposição a um predador, classificando-os em shy (tímido) ou bold (ousado) e em seguida estes indivíduos foram condicionados por um método simples de condicionamento clássico como forma de aprendizagem para posterior avaliação da memória. Os peixes shy foram então divididos em dois grupos, sendo que em um deles os peixes foram diariamente estressados por hipóxia, perseguição com rede ou confinamento (grupo shy-experimental) por 64 dias consecutivos, enquanto que no outro grupo os peixes permaneceram apenas isolados (grupo shy-controle) pelo mesmo período de tempo. O mesmo procedimento foi adotado com os peixes classificados como bold. Nesse mesmo período, testes de memória foram realizados em dias específicos, tanto nos grupos experimental quanto nos grupos controle. Ao final do experimento, reavaliamos se as personalidades se mantiveram. Obtivemos que o estresse agudo afetou a memória de aprendizado em peixes, principalmente em indivíduos com perfil de personalidade shy. CAPÍTULO 2 – Aqui desenvolvemos uma metodologia simples de condicionamento clássico facilmente aplicável em laboratórios de experimentação com peixes, quando comparados aos métodos descritos na literatura atual, onde os estímulos geralmente aplicados para condicioname... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: CHAPTER 1 - In this study we evaluated the effect of acute and chronic stress in learning memory of Nile tilapia with different personality profiles. Initially we defined the personality of the fish through the testo f new object and exposure to a predator, classifying them as shy or bold, and then these individuals were conditioned by a simple method of classical conditioning as a way of learning to evaluation of memory. The shy fish were divided into two groups, and in one group the fish were daily stressed by hypoxia, net chase or confinement (shy-experimental group) for 64 consecutive days, while in the other group the fish remained only isolated (shy-control group) for the same time period. The same procedure was adopted with fish classified as bold. During the same period, memory tests were performed on specific days, in both groups, experimental and control group. At the end of the experiment, we reevaluated whether the personalities held. We found that acute stress affected learning memory in fish, especially in individuals with shy personality profiles. CHAPTER 2 - Here we develop a classical conditioning methodology easily applicable in fish experimentation laboratories when compared to the methods described in the current literature, where the stimuli generally applied for conditioning (sound or light) can interfere with the responses of experimental animals present in the same laboratory. For this conditioning, we isolate the fish in individual aquariums and intro... (Complete abstract click electronic access below) / Doutor

The 21st century world is characterized by globalization, optimization, high performance demands, and continuous acceleration of processes. Not surprisingly, stress has steadily become more prevalent over the past years and has become a permanent challenge for many of us. Still we are always expected to perform at our best, and an impairment of cognitive performance can be devastating, particularly in the professional world. This ubiquity in daily life of chronic stress, cognitive demands, and their potential interactions was the motivation for this dissertation. Among cognitive processes executive functioning (EF) are of particular interest, as they represent set of fundamental cognitive abilities for mastering daily life. More precisely, EF is described as higher-order cognitive processes that control and coordinate complex cognitive tasks (Diamond, 2013; Miyake et al., 2000). The primary aim of this dissertation was to investigate the interplay between chronic stress and EF in detail. A three-year longitudinal cohort, the StressCog cohort, was established for this purpose. In order to understand the longitudinal interplay between chronic stress and EF, methodological foundations and cross-sectional matters had to be investigated first. As a result, this dissertation encompasses the following three studies: With classical laboratory designs, the estimation of generalizable and robust effects on the relationship between chronic stress and EF is impaired. Therefore, the StressCog study was set up to make use of internet-based data assessment within domestic environments. Study 1 addressed the feasibility of internet-based response time data, including the common concern that internet-based response time data collected in domestic environments is subject to increased data variability (Chetverikov & Upravitelev, 2016; Reips, 2002). To this end, performance measures collected in the laboratory were compared with measures collected in domestic environments. We found that a setting-related difference in the variability of conventional performance measures (i.e., response times and error rates), as well as diffusion model-based measures is only of small size. An overall increase of variance of approximately 5% was visible in domestic environments. However, as internet-based assessments allow for the recruitment of larger sample sizes (Reips, 2002) the loss of static power can be easily compensated. Therefore, the findings of Study 1 support the use of internet-based cognitive data collection in domestic environments. This formed a valuable basis regarding the collection and interpretation of the StressCog data used in Study 2 and Study 3. In order to get a broad picture of chronic stress the StressCog study aimed for multimethod assessment. The subjective (i.e., perceived) extent of chronic stress and conceptually related constructs were assessed by multiple self-reported measures. The objective (i.e., physiological) extent of chronic stress was assessed via hair cortisol concentration, which has been established as a widely accepted biological marker of chronic stress (E. Russell et al., 2012; Stalder & Kirschbaum, 2012). Surprisingly, however, multiple studies have shown that hair cortisol concentration is, at best, only weakly correlated with subjective chronic stress (Stalder et al., 2017; Staufenbiel et al., 2013; Weckesser et al., 2019). This lack of psychoendocrine covariance was addressed in Study 2 by investigating the construct validity of commonly used chronic stress instruments. A multidimensional item response theory approach was applied in order to display the overlap between items of commonly used measures of chronic stress, depressiveness, and neuroticism. A common latent scale covered the major amount of variance (40% to 48%). It appeared that the overlap of content is mainly based on fatigue, which is a core symptom of depressiveness. Similar to previously reported findings, the common latent scale displayed only a weak association with hair cortisol concentration. It can therefore be argued that items of self-reported chronic stress do not reflect the physiological (i.e., endocrine) aspect of chronic stress to a satisfactory extent. Thus, the results of Study 2 were a valuable basis for the interpretation of chronic stress data in Study 3. In Study 3, we investigated the cross-sectional association between chronic stress and EF. The study made use of data from the baseline assessment of the StressCog cohort (N = 514). Using structural equation modelling, we found no evidence for a meaningful association between chronic stress (i.e., self-reported measures and hair cortisol concentration) and a common latent EF factor. The results found in Study 3 were further supported by unpublished longitudinal StressCog data and analyses making use of diffusion model performance measures. Considering the mainstream of existing findings, which suggests chronic stress to be negatively associated with EF (e.g., Deligkaris et al., 2014; Sandi, 2013), an absence of an association between chronic stress and EF seems surprising. However, other existing findings support this perspective (Castaneda et al., 2011a; McLennan et al., 2016). Beyond this, the results of Study 1 and 2 help to explain why a lack of an association between chronic stress and EF is quite plausible. As within traditional, laboratory-based settings a recruitment of larger samples sizes is difficult and costly, most existing studies lack large, representative samples. In consequence, many findings are based on narrow sample characteristics. Supported by the findings of Study 1, the StressCog study made use of internet-based data collection, which led to the establishment of one the largest, population-based cohorts in the field. Thus, the results presented in this dissertation can be seen as much more robust and representative than many other studies that suggest opposing results. The findings of Study 2 allow for the assumption that many studies in the field make use of questionable self-report instruments and that subjective (i.e., self-reported) measures of chronic stress are only weakly related to objective (i.e., HCC) measures. In consequence, results always depend on the operationalization of the chronic stress measures being used. Caution is advised when comparing opposing results of different measures. With regard to our daily life demands, it may appear quite promising that no association between chronic stress and EF was found in this dissertation. However, these results should not be misunderstood. It has been demonstrated countless times that chronic stress can severely affect the human organism, causing various negative effects that go far beyond a possible impairment of cognitive abilities. Knowing that chronic stress can impair EF under certain circumstances leads to the central question of what conditions make stress toxic. In order to answer this question further systematic research is needed, in which representative samples and experimental study designs will be of crucial help. As long as these questions are not satisfactorily clarified, it seems best to deal with the challenges of chronic stress in a conscious and responsible manner.