Katarina Dedovic - Academia.edu (original) (raw)

Papers by Katarina Dedovic

ABSTRACT Psychological stress has an important impact on one's physical and mental health... more ABSTRACT Psychological stress has an important impact on one's physical and mental health. Activation of the hypothalamic-pituitary-adrenal (HPA) stress axis and the subsequent increase in the stress hormone cortisol constitutes the organism's main response to stress. Individual differences in stress response contribute to one's vulnerability and resilience to a host of physical and psychological ills. Understanding the regulatory networks underlying stress processing in both healthy and vulnerable populations is essential. The work presented in this thesis aimed to investigate neural correlates of psychological stress processing and the HPA axis function in samples of healthy individuals as well as those with distinct vulnerability to a stress-related illness, Major Depressive Disorder. Our literature review revealed that only studies using serial subtraction or the Montreal Imaging Stress Task (MIST), a task that combines mental arithmetic and negative social evaluation components, were able to induce a significant cortisol stress response. Deactivation in orbitofrontal regions and the limbic system were most consistently observed in response to psychological stress. Exposing healthy subjects to a new, event-related version of MIST revealed that reduction of brain activity in the limbic system observed previously was specifically associated with the processing of social evaluative threat, a key component of psychological stress. We then examined HPA axis function (both basal and reactive) and the HPA regulatory brain areas for evidence of dysregulation in a sample of healthy young adults who showed varying levels of depressive tendencies, but at subclinical levels. This was the first time that these concepts were assessed in a subclinically depressed population. The subjects with increased subclinical levels of depression showed impairments in HPA function (in a form of blunted cortisol awakening response and blunted stress response), as well as impairment in certain key regions within the HPA axis regulatory network (for e.g. small hippocampal volumes and dysregulated medial orbitofrontal cortex). I conclude the thesis by proposing a basic model of a neural network underlying stress processing in a healthy population, and also outline nodes at which this network might be affected in subclinically depressed populations. Some research avenues for future studies are also highlighted. L'expérience de stress psychologique peut compromettre la santé mentale et physiologique d'un individu. L'activation de l'axe hypothalamo-surrénalien, caractérisée par la libération subséquente de cortisol, constitue la principale réponse physiologique de stress. La susceptibilité ou la résilience pour un ensemble de maladies d'ordre physiques ou psychologiques est influencée par la variabilité interindividuelle dans la réponse de stress. Il est donc essentiel de comprendre le fonctionnement des systèmes régulateurs de la réponse de stress comparativement chez des sujets sains et vulnérables. Le travail présenté dans cette thèse investigue les processus neuronaux et endocrinologiques du stress psychologique chez des sujets sains exprimant divers degré de susceptibilité à la dépression majeure, une psychopathologie reliée au stress. Notre revue de la littérature suggère que l'exposition à une épreuve de soustraction en série de même que l'exposition au Montreal Imaging Stress Task (MIST), une épreuve de calcul mentale dans lequel le sujet est évalué négativement, peuvent induire une augmentation significative de cortisol. Au niveau neuronal, la réponse de stress psychologique se manifeste par une réduction de l'activité du cortex orbitofrontal et des régions du système limbique. L'exposition de sujets sains à une nouvelle version du MIST, employant un paradigme événementiel, a démontré que la réduction de l'activité du système limbique était spécifiquement associée aux éléments de menace psychosocial, une composante clé dans l'induction de la réponse de stress. Nous avons ensuite étudié l'activité de l'axe hypothalamo-surrénalien, (basale et réactive) en relation avec les régions cérébrales régulatrices afin d'observer certaines irrégularités chez de jeunes adultes sains qui présente divers degré de susceptibilité au développement de trouble dépressifs tout en demeurant sous le seuil clinique. Les sujets présentant un profil dépressif sous clinique élevée on démontrer un dysfonctionnement de l'axe hypothalamo-surrénalien, (une suppression des niveaux de cortisol à l'éveil et en réponse de stress) ainsi que l'altération de régions cérébrales régulatrices de la réponse de stress (volume hippocampique réduit, dysfonctionnement de l'activité du cortex orbitofrontale médial). Je conclue cette thèse en proposant un modèle d'interaction cérébrale impliqué dans la réponse de stress chez des sujets sains en soulignant les possibles sites de…

Journal of Psychiatry & Neuroscience, 2010

Substance Abuse: Research and Treatment, 2015

Driving while impaired (DWI) is a grave and persistent high-risk behavior. Previous work demonstr... more Driving while impaired (DWI) is a grave and persistent high-risk behavior. Previous work demonstrated that DWI recidivists had attenuated cortisol reactivity compared to non-DWI drivers. This suggests that cortisol is a neurobiological marker of high-risk driving. The present study tested the hypothesis that this initial finding would extend to first-time DWI (fDWI) offenders compared to non-DWI drivers. Male fDWI offenders ( n = 139) and non-DWI drivers ( n = 31) were exposed to a stress task, and their salivary cortisol activity (total output and reactivity) was measured. Participants also completed questionnaires on sensation seeking, impulsivity, substance use, and engagement in risky and criminal behaviors. As hypothesized, fDWI offenders, compared to non-DWI drivers, had lower cortisol reactivity; fDWI offenders also showed lower total output. In addition, cortisol activity was the most important predictor of group membership, after accounting for alcohol misuse patterns and c...

Driving while impaired by alcohol (DWI) is a persistent yet preventable public health problem. Re... more Driving while impaired by alcohol (DWI) is a persistent yet preventable public health problem. Recent evidence indicates an increasing number of females engaging in DWI behaviour and distinct sex-based trajectories, though sex-based analysis is infrequent in DWI research, especially with respect to the role of cognitive processes. The current study investigated associations between sex, cortical thickness analysis using high resolution Magnetic Resonance Imaging (MRI) and psychological functioning in DWI offenders. It was hypothesized that male offenders possess brain features consistent with impaired executive control, while female offenders show more signs of alcohol misuse and psychological dysfunction. 31 male and 16 female DWI offenders, and 31 male and 31 female non-DWI drivers were recruited. All subjects underwent T1 high resolution MRI scanning and cortical thickness analysis using the CIVET pipeline and assessment on sociodemographic, alcohol misuse, impulsivity, and psych...

International journal of adolescent medicine and health, Jan 13, 2018

Adolescent risky driving is a significant burden on public health. Young offenders (i.e. under cu... more Adolescent risky driving is a significant burden on public health. Young offenders (i.e. under custody and supervision of the criminal justice system) may be particularly vulnerable, but research is scant. Previous work indicated that blunted cortisol reactivity to stress is a marker of risk-taking predisposition, including risky driving. In this study, we hypothesized that young offenders display higher levels of risky driving than a non-offender comparison group, and that cortisol reactivity contributes to the variance in risky driving independent of other associated characteristics (i.e. impulsivity, risk taking, alcohol and drug use). We found that young offenders (n = 20) showed riskier driving in simulation than comparison group (n = 9), and blunted cortisol reactivity was significantly associated with risky driving. The results suggest young offenders are prone to risky driving, and that individual differences in the cortisol stress response may be an explanatory factor.

Social Cognitive and Affective Neuroscience, 2016

Social stratification has important implications for health and well-being, with individuals lowe... more Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions.

Neuroscience letters, Jan 24, 2016

Some sex differences have been detected in driving while impaired by alcohol (DWI) offenders. How... more Some sex differences have been detected in driving while impaired by alcohol (DWI) offenders. However, understanding of the key factors contributing to DWI among male and female drivers remains elusive, limiting development of targeted interventions. Sex-based neurocognitive analyses could provide the much-needed insight. We examined whether male DWI offenders show cortical thickness anomalies that differ from those in female DWI offenders, when compared to their respective controls. Moderating role of sex and alcohol use on DWI status was also investigated. Sixty-one DWI offenders (29 male; 32 female) and 58 controls (29 male; 29 female) completed an anatomical brain scan and assessments on other relevant characteristics. Only male DWI offenders had reduced cortical thickness in the right dorsal posterior cingulate cortex (PCC), a region involved in cognitive control. Lower cortical thickness was associated with increased odds of DWI status only among males who have not engaged in ...

Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2009

Recent neuroimaging studies aimed at investigating effects of psychological stress on the neural ... more Recent neuroimaging studies aimed at investigating effects of psychological stress on the neural activity have used a range of experimental paradigms to elicit an acute stress response. The goal of this review is to, first, summarize results from these studies from a perspective of task design and, second, assess the appropriateness of the different stress tasks used. We completed a PubMed search on recent articles that have examined the effects of psychological stress on neural processes in a neuroimaging environment. Selected articles were arranged according to the stress task used in the following categories: script-driven stress stimuli, Stroop colour-word interference task, speech in front of an audience, serial subtraction, and Montreal Imaging Stress Task (MIST). Only studies using serial subtraction or the MIST were able to induce a significant cortisol stress response in their participants. Most consistent findings include decreased activity in orbitofrontal regions in resp...

Journal of psychiatry & neuroscience : JPN, 2005

We developed a protocol for inducing moderate psychologic stress in a functional imaging setting ... more We developed a protocol for inducing moderate psychologic stress in a functional imaging setting and evaluated the effects of stress on physiology and brain activation. The Montreal Imaging Stress Task (MIST), derived from the Trier Mental Challenge Test, consists of a series of computerized mental arithmetic challenges, along with social evaluative threat components that are built into the program or presented by the investigator. To allow the effects of stress and mental arithmetic to be investigated separately, the MIST has 3 test conditions (rest, control and experimental), which can be presented in either a block or an event-related design, for use with functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). In the rest condition, subjects look at a static computer screen on which no tasks are shown. In the control condition, a series of mental arithmetic tasks are displayed on the computer screen, and subjects submit their answers by means of a resp...

Brain, Behavior, and Immunity, 2015

Psychological stress is implicated in the etiology of many common chronic diseases and mental hea... more Psychological stress is implicated in the etiology of many common chronic diseases and mental health disorders. Recent research suggests that inflammation may be a key biological mediator linking stress and health. Nevertheless, the neurocognitive pathways underlying stress-related increases in inflammatory activity are largely unknown. The present study thus examined associations between neural and inflammatory responses to an acute laboratory-based social stressor. Healthy female participants (n = 31) were exposed to a brief episode of stress while they underwent an fMRI scan. Blood samples were taken before and after the stressor, and plasma was assayed for markers of inflammatory activity. Exposure to the stressor was associated with significant increases in feelings of social evaluation and rejection, and with increases in levels of inflammation. Analyses linking the neural and inflammatory data revealed that heightened neural activity in the amygdala in response to the stressor was associated with greater increases in inflammation. Functional connectivity analyses indicated that individuals who showed stronger coupling between the amygdala and the dorsomedial prefrontal cortex (DMPFC) also showed a heightened inflammatory response to the stressor. Interestingly, activity in a different set of neural regions was related to increases in feelings of social rejection. These data show that greater amygdala activity in response to a stressor, as well as tighter coupling between the amygdala and the DMPFC, are associated with greater increases in inflammatory activity. Results from this study begin to identify neural mechanisms that might link stress with increased risk for inflammation-related disorders such as cardiovascular disease and depression.

Neuroscience, 2013

Various studies have shown that increased activity of the hypothalamic-pituitary-adrenal (HPA) ax... more Various studies have shown that increased activity of the hypothalamic-pituitary-adrenal (HPA) axis can predict the onset of adolescent depressive symptomatology. We have previously shown that adolescents making the transition to high school present a significant increase in cortisol levels, the main product of HPA axis activation. In the present study, we evaluated whether a school-based education program developed according to the current state of knowledge on stress in psychoneuroendocrinology decreases cortisol levels and/or depressive symptoms in adolescents making the transition to high school. Participants were 504 Year 7 high school students from two private schools in the Montreal area. Adolescents of one school were exposed to the DeStress for Success Program while adolescents from the other school served as controls. Salivary cortisol levels and depressive symptomatology were measured before, immediately after as well as 3 months after exposure to the program. Measures of negative mood were obtained at baseline in order to determine whether adolescents starting high school with specific negative moods were differentially responsive to the program. The results show that only adolescents starting high school with high levels of anger responded to the intervention with a significant decrease in cortisol levels. Moreover, we found that adolescents who took part in the intervention and showed decreasing cortisol levels following the intervention (responders) were 2.45 times less at risk to suffer from clinical and subclinical depressive states three months postintervention in comparison to adolescents who showed increasing cortisol levels following the intervention (nonresponders). This study provides the first evidence that a school-based program on stress is effective at decreasing cortisol levels and depressive symptomatology in adolescents making the transition to high school and it helps explain which adolescents are sensitive to the program and what are some of the characteristics of these individuals. This article is part of a Special Issue entitled: Stress and the Adolescent Brain.

Social Cognitive and Affective Neuroscience, 2014

Processing self-related material recruits similar neural networks regardless of whether the self-... more Processing self-related material recruits similar neural networks regardless of whether the self-relevance is made explicit or not. However, when considering the neural mechanisms that distinctly underlie cognitive and affective components of self-reflection, it is still unclear whether the same mechanisms are involved when self-reflection is explicit or implicit, and how these mechanisms may be modulated by individual personality traits, such as self-esteem. In the present functional MRI study, 25 participants were exposed to positive and negative words that varied with respect to the degree of self-relevance for each participant; however, the participants were asked to make a judgment about the color of the words. Regions-of-interest analysis showed that medial prefrontal cortex (mPFC) and posterior cingulate cortex were associated with gauging the self-relevance of information. However, no main effect of valence or an interaction effect between self-relevance and valence was observed. Further, positive correlations were observed between levels of self-esteem and response within dorsal mPFC (dmPFC) both in the contrast positive-high in self-relevance trials vs positivelow in self-relevance trials and in the contrast negative-low in self-relevance trials vs positive-low in self-relevance trials. These results suggested that the activation of dmPFC may be particularly associated with the processes of self-positivity bias.

Psychoneuroendocrinology, 2010

The metabolic effects of stress are known to have significant health effects in both humans and a... more The metabolic effects of stress are known to have significant health effects in both humans and animals. Most of these effects are mediated by the major stress hormonal axis in the body, the hypothalamic-pituitary-adrenal (HPA) axis. Within the central nervous system (CNS), the hippocampus, the amygdala and the prefrontal cortex as part of the limbic system are believed to play important roles in the regulation of the HPA axis. With the advent of structural and functional neuroimaging techniques, the role of different CNS structures in the regulation of the HPA axis can be investigated more directly. In the current paper, we summarize the findings obtained in our laboratory in the context of stress and HPA axis regulation. Our laboratory has developed and contributed to the development of manual and automated segmentation protocols from structural magnetic resonance imaging (MRI) scans for assessment of hippocampus, amygdala, medial temporal lobe and frontal lobe structures. Employing these protocols, we could show significant age-related changes in HC volumes, which were different between men and women, with pre-menopausal women showing smaller age-related volume decline compared to men. We could recently extent these findings by showing how estrogen therapy after menopause leads to higher volumes in the HC. Investigating possible neurotoxicity effects of steroids, we showed effects of long-term steroid exposure on HC volumes, and investigated variability of HC volumes in relation to HPA axis regulation in young and elderly populations. Here, we were able to follow-up from non-imaging studies showing that subjects low in self-esteem have higher cortisol stress responses, and the HC emerged as the critical link between these variables. Recently, we have made two more important discoveries with regard to HC volume: we could show that HC volume is as variable in young as it is in older adults, in subjects ranging in age from 18 to 80 years. Also, we have linked birth weight and maternal care to HC volumes in young adults, demonstrating the effects of variations in maternal care on the integrity of the CNS. Besides structural assessments, there is increasing interest in functional techniques to investigate possible links between CNS activity and HPA axis regulation. These two approaches complement each other; some aspects of HPA axis regulation might be linked to the integrity of a specific CNS structure, while other aspects might be linked to the function of a specific structure with no involvement of CNS morphology. Thus, we have developed a mental arithmetic stress task that can be employed in functional neuroimaging studies, and have used it in a number of functional neuroimaging studies. Employing positron emission tomography (PET), we were able to demonstrate that stress causes dopamine release if subjects reported low maternal care early in life. Finally, employing the task in functional magnetic resonance imaging (fMRI), we could show how exposure to stress and activation of the HPA axis are associated with decreased activity in major portions of the limbic system, a result that allows to speculate on the effects of stress on cognitive and emotional regulation in the brain. Taken together, the use of neuroimaging techniques in Psychoneuroendocrinology opens exciting new possibilities for the investigation of stress effects in the central nervous system.

Neurocase, 2010

Self-esteem, a value one places on oneself, influences one&amp;amp;amp;amp;amp;amp;amp;am... more Self-esteem, a value one places on oneself, influences one&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s cognitive, emotional and behavioral responses across various situations. In the case of risky decision-making, high self-esteem (SE) individuals rely on their positive self-views and tend to be less defensive in response to a risky task; low SE individuals, on the contrary, tend to have fewer accessible positive resources and thus, are more prone to risk-aversion. While past studies have provided evidence for a link between self-esteem and a behaviorally-risky response, no study has explored the relation between self-esteem and the electrophysiological correlates of risky response. Therefore, the current study investigated the correlates of risky decision-making in high SE compared to low SE participants using event-related potentials (ERP) technology in 28 undergraduate students playing a blackjack game. The results showed that there was no difference between the high SE participants and the low SE participants with respect to the behavioral assessments of the risk-taking decision-making. However, for the electrophysiological data, we observed that the amplitude of P2 (150-300 ms) was more positive in the high SE participants compared to the low SE participants over the central-posterior scalp region. Dipole source analysis indicated that this positive component was generated in posterior cingulate cortex (PCC). These findings suggest that the high SE participants experienced more emotional signals than the low SE participants during decision-making.

Hippocampus, 2009

Increased activation of the hypothalamus pituitary adrenal (HPA) axis, marked by increased secret... more Increased activation of the hypothalamus pituitary adrenal (HPA) axis, marked by increased secretion of cortisol, is a biological marker of psychological stress. It is well established that the hippocampus plays an important role in the regulation of HPA axis activity. The relationship between cortisol (stress-related elevation or exogenous administration) and the hippocampal-related cognitive function is often examined. However, few human studies to date have examined the effect of stress on hippocampal activity and the interactions between stress-induced activation of the HPA axis and hippocampal function during different phases of cognitive function. On the basis of our previous work, we hypothesized that group differences in stress-sensitivity relate to differences in hippocampal-related stress-integration. To test this hypothesis, we conducted a functional MRI study using tasks known to involve the hippocampal formation: novel-picture encoding, psychological stress, and paired-picture recognition. On the basis of their cortisol responses to stress, we divided subjects into stress-responders (increase in cortisol, n 5 9) and nonresponders (decrease in cortisol, n 5 10). Responders showed higher hippocampal deactivation during the stress task and lower recognition scores due to a larger number of misses. Intriguingly, stress-responders showed significant differences in hippocampal activation already prior to stress, with higher levels of hippocampal activity during the picture encoding. Although effects of both cortisol and hippocampal activation on recognition were present in responders, similar effects were absent in the nonresponder group. Our results indicate that hippocampus plays an important role in adaptive behavioral responses. We hypothesize that states of hippocampal activation prior to stress might reflect states of vigilance or anxiety, which might be important for determining interindividual differences in subsequent stress response and cognitive performance. V

Psychopharmacology, 2010

Rationale Growing evidence from animal and human studies suggests a profound and long-lasting inf... more Rationale Growing evidence from animal and human studies suggests a profound and long-lasting influence of early life experiences-ranging from variations in parenting behavior to severe adversity-on hypothalamic-pituitaryadrenal axis function. Objectives The aim of the current investigation was to examine the association between naturally occurring variations in early life parental care and the cortisol awakening response (CAR), afternoon/evening cortisol output and key psychological variables in a sample of healthy young adults. Methods Fifty-eight (19 male and 39 female) participants between 18 and 30 years of age completed psychological questionnaires and collected saliva at awakening, 30 min thereafter and at 3 p.m., 6 p.m., and 9 p.m. on three nonconsecutive weekdays. Results Participants with low (compared to high) parental care experiences exhibited an increased CAR, increased afternoon/evening cortisol output, decreased self-esteem, and increased depressive symptomatology and anxiety. Conclusions We suggest that the elevated CAR and afternoon/evening cortisol levels might reflect a biological correlate of adversity-induced vulnerability for psychopathology. This study is first to show an association between the retrospective perception of early life parental care and cortisol circadian rhythms in healthy young adults.

Neuropsychologia, 2012

Self-esteem can be defined as evaluations that individuals make about their worth as human beings... more Self-esteem can be defined as evaluations that individuals make about their worth as human beings. These evaluations are in part based on how we evaluate ourselves on our abilities, values, opinions, etc. compared with others or our past or ideal self; and they are also influenced by a thought that what others may think about us. Studies to date investigating the neural mechanisms underlying individual differences in self-esteem have focused mostly on the latter process (i.e. on how self-esteem is associated with neural correlates of processing feedback from others). However, given that people spend a lot of time thinking about themselves and evaluating their worth, we aimed to investigate neural mechanism underlying the association between levels of self-esteem and processing of self-relevant information. Seventeen participants completed a functional magnetic resonance imaging (fMRI) scan during which they were asked to evaluate whether a given statement is true about them (Self), an acquaintance of theirs (Other), or about general knowledge (Semantic). A whole brain correlational analysis revealed a significant negative correlation between levels of self-esteem and changes in activation of dorsal anterior cingulate gyrus (dACC, BA32) in response to evaluating self-relevant information (Self versus Other contrast). This result extends previous findings implicating this region in the association between processing evaluative feedback and levels of self-esteem and suggests that activity in this region is affected by self-esteem levels also when individuals are engaged in self-referencing and self-evaluation. Future studies should investigate whether these associations are affected differently based on valence of self-evaluations.

NeuroImage, 2009

The hypothalamic-pituitary-adrenal (HPA) axis is the major endocrine stress axis of the human org... more The hypothalamic-pituitary-adrenal (HPA) axis is the major endocrine stress axis of the human organism. Cortisol, the final hormone of this axis, affects metabolic, cardiovascular and central nervous systems both acutely and chronically. Recent advances in neuroimaging techniques have led to the investigation of regulatory networks and mechanisms of cortisol regulation in the central nervous system in human populations. In the following review, results from human and animal studies are being presented that investigate the specific role of hippocampus (HC), amygdala (AG), prefrontal cortex (PFC), and brainstem nuclei in cortisol regulation in response to stress. In general, the types of stressors need to be distinguished when discussing the contributions of these structures in regulating the HPA axis. We propose a basic framework on how these structures communicate as a network to regulate cortisol secretion in response to psychological stress. Furthermore, we review critical studies that have substantially contributed to the literature. Possible future research avenues in the field of neuroimaging of cortisol regulation are discussed. In combination with investigations on genetic and environmental factors that influence the development of the HPA axis, this emerging new research will eventually allow the formulation of a more comprehensive framework of functional neuroanatomy of cortisol regulation.