- Email: [email protected]
The effects of cortisol on human fear memory reconsolidation
R. Reynolds / Psychoneuroendocrinology 61 (2015) 1–78
Objective: Describe the specific and common etiology of the CAR, awakening and cortisol change occurring from morning to evening in an age-homogenous sample of adolescents. Methods: More than 500 participants of the Québec Newborn Twin Study, a representative 1995–1998 cohort of families with twins in Canada, collected saliva at awakening, 30 min later, at the end of afternoon and in the evening over four collection days. Results: Multivariate Cholesky model showed both specific and common sources of variance between the CAR, awakening and cortisol diurnal change. The CAR had the strongest heritability (50%) which, for the most part, did not overlap with the other indicators. Conversely, awakening and diurnal change showed similar genetic and environmental contributions (A = .28, C = .15, E = .57; A = .31, C = .20, E = .49, respectively) of which all partially overlapped. Conclusion: Our study extends previous findings by unravelling differences between the latent etiologies of the CAR and the rest of the diurnal cycle, enlightening the search of the genes and environments that are at play and the mechanisms relating these factors to physical and mental health. http://dx.doi.org/10.1016/j.psyneuen.2015.07.505
PO58 Socioeconomic status and inattention: The role of the HPA-axis Ashley R. McDonald ∗ , Celina Joos, Martha E. Wadsworth Pennsylvania State University, University Park, PA, USA Attention problems during pre-adolescence is a risk factors for negative academic achievement in adolescence (Birchwood and Daley, 2012). Socioeconomic status (SES) has been indicated as a risk factor for the development of inattention (Pastor et al., 2015). Dysregulation of the hypothalamic–pituitary–adrenal (HPA) is associated with both income status and HPA-axis activity but the relationship between SES, HPA-axis and inattention in preadolescents has yielded inconsistent results in non-clinical samples (Sondeijker et al., 2005). The purpose of this study was to explore the effects of SES, HPA-axis activity and their interaction on inattention problems in a sample of pre-adolescents (8–12 years old, Mage = 10.6 years, SD = .69) in non-metropolitan areas. 73 preadolescents completed the Trier Social Stress Task – Children (TSST-C, Kirschbaum et al., 1993) and stress reactivity was assessed using salivary cortisol sampling at 6 time points. Parents completed the Behavioral Assessment System for Children (BASC-2) and a demographic questionnaire from which income-to-needs ratio (INR) was calculated as a measure of SES. As a set with gender as a covariate, INR, cortisol AUCg, and their interaction predicted inattention problems, F(4,52) = 3.676, p = 0.10, 2 = 0.007. INR significantly predicted inattention such that those with higher INR had fewer attention problems, B = −1.4, t(56) = −2.2, p = 0.03, 2 = 0.02. Lower CAUCg is moderately protective for adolescents regardless of SES, B = −0.387, t(56) = −1.7, p = 0.01, 2 = 0.05. More research is needed to better understand the mechanism by which low HPA-axis activity is protective for pre-adolescents from lowSES families. http://dx.doi.org/10.1016/j.psyneuen.2015.07.506
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PO59 Biomarkers in the HPA axis and inflammatory pathways for suicidal behavior in youth Nadine Melhem 1,∗ , Sara Munroe 2 , Anna Marsland 3 , Katrina Krijna 3 , David Brent 1 , Antoine Douaihy 1 , Frank DiPietro 2 , Rasim Diller 2 , Henry Driscoll 2 1
University of Pittsburgh School of Medicine, Pittsburgh, USA 2 University of Pittsburgh Medical Center, Pittsburgh, USA 3 University of Pittsburgh, Department of Psychology, Pittsburgh, USA Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation is one of the biological pathways implicated in suicidal behavior and is associated with 4.5-fold increased risk for suicide. However, It is not clear whether such dysregulation exists prior to suicidal behavior or is a consequence of a suicide attempt. We recruited psychiatric inpatients, aged 15–30 years, admitted for suicide attempt (SA, n = 38), inpatients admitted for suicidal ideation with no previous history of attempts (SI, n = 40), and healthy controls (n = 40) and collected hair samples to measure hair cortisol concentrations (HCC). HCC provides a retrospective assessment of cortisol secretion over the past few months and thus, in our study design, prior to suicide attempt in SA. We also measured gene expression in the HPA axis and inflammatory pathways and C-Reactive Protein (CRP). We find SA to have significantly lower HCC (Cohen’s d = −0.79, p = 0.03) compared to SI (Cohen’s d = 0.1, p = 0.82) and controls although SA and SI were similar on actual stressors and perceived stress prior to admission. SA also showed significantly lower glucocorticoid receptor or GR mRNA (Cohen’s d = −0.43, p = 0.03), higher Tumor Necrosis Factor-a or TNF-a mRNA (Cohen’s d = 0.75, p = 0.006), and higher levels of CRP (Cohen’s d = 0.84, p = 0.04) compared to SI and controls. These results suggest a blunted HPA axis activity and an inability to mount an adaptive response to stress in suicide attempters that is accompanied by an activation of the inflammatory pathways. Blunted or insufficient glucocorticoid signaling could put patients with psychiatric disorders at risk for suicidal behavior when faced with stressors. http://dx.doi.org/10.1016/j.psyneuen.2015.07.507 Memory, Cognition and the Brain PO60 The effects of cortisol on human fear memory reconsolidation Shira Meir Drexler 1,2,∗ , Christian J. Merz 1 , Tanja C. Hamacher-Dang 1,2 , Oliver T. Wolf 1 1
Department of Cognitive Psychology, Ruhr-University Bochum, Bochum, Germany 2 International Graduate School of Neuroscience, Ruhr-University Bochum, Bochum, Germany Reactivation of an already consolidated memory item via its retrieval can make it once again fragile and susceptible to interruption until it reconsolidates. During this period, reactivated memories can be altered (enhanced, impaired or otherwise updated) by behavioural or pharmacological manipulations. Animal studies suggest cortisol as possible modulator of reactivated memories, but its effects on human fear memory reconsolidation
44
R. Reynolds / Psychoneuroendocrinology 61 (2015) 1–78
are largely unknown, and are therefore the aim of the present study. Forty healthy males were assigned to one of three groups (Reactivation + Cortisol, Reactivation + Placebo, Cortisol + No-reactivation) and were tested on a three-day reconsolidation design. For fear acquisition, three geometrical shapes were used as conditioned stimuli (CS): two stimuli (CS1+, CS2+) were paired with an electrical shock; one stimulus (CS−) was never paired with a shock. On the second day, cortisol/placebo was administered prior to a single unreinforced presentation (memory reactivation) of CS1+, one of the previously reinforced CS+. On the third day, following extinction and reinstatement by shock, the return of fear to all stimuli was tested. Our results revealed a more pronounced reinstatement of the CS1+ in the Reactivation + Cortisol group, suggesting an enhancing effect of cortisol on the reactivated fear memory. The effect was highly specific to the reactivated CS1+ and did not affect the nonreactivated CS2+. The findings indicate a similarity between the processes mediating initial consolidation and reconsolidation following reactivation. These findings will be compared to the results of currently ongoing reconsolidation studies from our lab. Possible theoretical and clinical implications will be discussed. http://dx.doi.org/10.1016/j.psyneuen.2015.07.508
PO61 Fear conditioning, social groups and stress Christian Merz 1,2,∗ , Oliver Wolf 2 1 2
University Trier, Trier, Germany Ruhr Unvierstiy Bochum, Bochum, Germany
The stress hormone cortisol has been shown to reduce retrieval of fear- memories. Repeated pairings with an aversive unconditioned stimulus (UCS) with a neutral stimulus lead to the acquisition of fear-related properties of this now conditioned stimulus (CS+). Previously, it has been shown that in- and outgroup faces used as conditioned stimuli in a fear conditioning design evoke distinct response patterns. In this study, we investigated how acute stress intervenes with this social fear conditioning design. In the acquisition phase, 33 healthy men were confronted repeatedly with two in-group and two outgroup faces, one of each was paired with an electrical stimulation (UCS), representing the CS+, whereas the other was not coupled to the UCS (CS−). In the extinction phase, all CS were presented again but with no UCS application. On the next day, participants were randomly assigned to a stress or control condition. We tested for different extinction retrieval of in- and outgroup CS during increasing cortisol concentrations after stress induction (socially evaluated cold pressor test). Indeed, acute stress modulated extinction retrieval on the second day: whereas the control group showed a differentiation in skin conductance responses between in- and outgroup faces, stress abolished this differentiation. Overall, we could demonstrate that acute stress inhibits the retrieval of combined socially and fear-relevant information. Assumedly, the influence of stress hormones on the hippocampus is responsible for these effects given its role in fear retrieval, binding and context processing. http://dx.doi.org/10.1016/j.psyneuen.2015.07.509
PO62 Does stimulation of the mineralocorticoid receptor influence autobiographic memory retrieval? A study in patients with major depression, patients with borderline personality disorder and healthy controls Juliane Fleischer ∗ , Katja Wingenfeld, Linn Kühl, Kim Hinkelmann, Stefan Roepke, Christian Otte Charité Universitätsmedizin, Berlin, Germany There is evidence that stimulation of mineralocorticoid receptors (MR) enhances memory in healthy subjects and in patients with major depression (MDD). In contrast, in patients with borderline personality disorder (BPD) this effect seems to be taskdependent. Aim of this study was to investigate the effect of MR stimulation on autobiographic memory retrieval in healthy individuals, patients with MDD, and patients with BPD. We conducted a placebo-controlled study in an intra-individual cross-over design. Twenty-four patients with MDD, 37 patients with BPD and 67 healthy participants completed an autobiographic memory test after receiving 0.4 mg fludrocortisone, a mineralocorticoid receptor agonist, or placebo in a randomized order. Healthy subjects, patients with MDD, and patients with BPD did not differ in their autobiographic memory retrieval. Furthermore, the administration of fludrocortisone had no effect on autobiographic memory. In conclusion, the stimulation of MR does not influence autobiographic memory retrieval in healthy subjects, patients with MDD, and patients with BPD. Our results do not support a role of MR in autobiographic memory. http://dx.doi.org/10.1016/j.psyneuen.2015.07.510
PO63 Psychosocial stress affects attentional control and neural oscillatory activity Ismael Palacios-Garcia 1,∗ , Mario Villena-Gonzalez 1 , German Campos-Arteaga 1 , Claudio Artigas 1 , Karina Jaramillo 2 , Jaime Silva 2 , Eugenio Rodriguez 1 1
Pontificia Universidad Católica de Chile, Santiago, RM, Chile 2 Universidad del Desarollo, Santiago, RM, Chile Every day we have to divide our limited attentional resources into different external and internal demands. Considering that psychosocial stress promotes the allocation of attentional resources to threat-related stimuli such as the social evaluation, the aim of the study is (1) to investigate if psychosocial stress affects the behavioral performance in an attentional shifting task and (2) to search, under an exploratory approach, some of its neural correlates. 40 healthy participants were exposed to either an electroencephalogram-compatible version of the Trier Social Stress Test (TSST) or a control protocol. Additionally, immediately before and after these protocols, subject participated in the attentional shifting task. Manipulation checks were verified through the changes of the heart rate, salivary concentration of cortisol and the score in the anxiety scale in the “stress” condition respect the control. When we compared the behavioral performance in the attentional task prior and after both conditions, we found that the control group showed a clear improvement in performance, characterized by a relative increase of correct trials and
Objective: Describe the specific and common etiology of the CAR, awakening and cortisol change occurring from morning to evening in an age-homogenous sample of adolescents. Methods: More than 500 participants of the Québec Newborn Twin Study, a representative 1995–1998 cohort of families with twins in Canada, collected saliva at awakening, 30 min later, at the end of afternoon and in the evening over four collection days. Results: Multivariate Cholesky model showed both specific and common sources of variance between the CAR, awakening and cortisol diurnal change. The CAR had the strongest heritability (50%) which, for the most part, did not overlap with the other indicators. Conversely, awakening and diurnal change showed similar genetic and environmental contributions (A = .28, C = .15, E = .57; A = .31, C = .20, E = .49, respectively) of which all partially overlapped. Conclusion: Our study extends previous findings by unravelling differences between the latent etiologies of the CAR and the rest of the diurnal cycle, enlightening the search of the genes and environments that are at play and the mechanisms relating these factors to physical and mental health. http://dx.doi.org/10.1016/j.psyneuen.2015.07.505
PO58 Socioeconomic status and inattention: The role of the HPA-axis Ashley R. McDonald ∗ , Celina Joos, Martha E. Wadsworth Pennsylvania State University, University Park, PA, USA Attention problems during pre-adolescence is a risk factors for negative academic achievement in adolescence (Birchwood and Daley, 2012). Socioeconomic status (SES) has been indicated as a risk factor for the development of inattention (Pastor et al., 2015). Dysregulation of the hypothalamic–pituitary–adrenal (HPA) is associated with both income status and HPA-axis activity but the relationship between SES, HPA-axis and inattention in preadolescents has yielded inconsistent results in non-clinical samples (Sondeijker et al., 2005). The purpose of this study was to explore the effects of SES, HPA-axis activity and their interaction on inattention problems in a sample of pre-adolescents (8–12 years old, Mage = 10.6 years, SD = .69) in non-metropolitan areas. 73 preadolescents completed the Trier Social Stress Task – Children (TSST-C, Kirschbaum et al., 1993) and stress reactivity was assessed using salivary cortisol sampling at 6 time points. Parents completed the Behavioral Assessment System for Children (BASC-2) and a demographic questionnaire from which income-to-needs ratio (INR) was calculated as a measure of SES. As a set with gender as a covariate, INR, cortisol AUCg, and their interaction predicted inattention problems, F(4,52) = 3.676, p = 0.10, 2 = 0.007. INR significantly predicted inattention such that those with higher INR had fewer attention problems, B = −1.4, t(56) = −2.2, p = 0.03, 2 = 0.02. Lower CAUCg is moderately protective for adolescents regardless of SES, B = −0.387, t(56) = −1.7, p = 0.01, 2 = 0.05. More research is needed to better understand the mechanism by which low HPA-axis activity is protective for pre-adolescents from lowSES families. http://dx.doi.org/10.1016/j.psyneuen.2015.07.506
43
PO59 Biomarkers in the HPA axis and inflammatory pathways for suicidal behavior in youth Nadine Melhem 1,∗ , Sara Munroe 2 , Anna Marsland 3 , Katrina Krijna 3 , David Brent 1 , Antoine Douaihy 1 , Frank DiPietro 2 , Rasim Diller 2 , Henry Driscoll 2 1
University of Pittsburgh School of Medicine, Pittsburgh, USA 2 University of Pittsburgh Medical Center, Pittsburgh, USA 3 University of Pittsburgh, Department of Psychology, Pittsburgh, USA Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation is one of the biological pathways implicated in suicidal behavior and is associated with 4.5-fold increased risk for suicide. However, It is not clear whether such dysregulation exists prior to suicidal behavior or is a consequence of a suicide attempt. We recruited psychiatric inpatients, aged 15–30 years, admitted for suicide attempt (SA, n = 38), inpatients admitted for suicidal ideation with no previous history of attempts (SI, n = 40), and healthy controls (n = 40) and collected hair samples to measure hair cortisol concentrations (HCC). HCC provides a retrospective assessment of cortisol secretion over the past few months and thus, in our study design, prior to suicide attempt in SA. We also measured gene expression in the HPA axis and inflammatory pathways and C-Reactive Protein (CRP). We find SA to have significantly lower HCC (Cohen’s d = −0.79, p = 0.03) compared to SI (Cohen’s d = 0.1, p = 0.82) and controls although SA and SI were similar on actual stressors and perceived stress prior to admission. SA also showed significantly lower glucocorticoid receptor or GR mRNA (Cohen’s d = −0.43, p = 0.03), higher Tumor Necrosis Factor-a or TNF-a mRNA (Cohen’s d = 0.75, p = 0.006), and higher levels of CRP (Cohen’s d = 0.84, p = 0.04) compared to SI and controls. These results suggest a blunted HPA axis activity and an inability to mount an adaptive response to stress in suicide attempters that is accompanied by an activation of the inflammatory pathways. Blunted or insufficient glucocorticoid signaling could put patients with psychiatric disorders at risk for suicidal behavior when faced with stressors. http://dx.doi.org/10.1016/j.psyneuen.2015.07.507 Memory, Cognition and the Brain PO60 The effects of cortisol on human fear memory reconsolidation Shira Meir Drexler 1,2,∗ , Christian J. Merz 1 , Tanja C. Hamacher-Dang 1,2 , Oliver T. Wolf 1 1
Department of Cognitive Psychology, Ruhr-University Bochum, Bochum, Germany 2 International Graduate School of Neuroscience, Ruhr-University Bochum, Bochum, Germany Reactivation of an already consolidated memory item via its retrieval can make it once again fragile and susceptible to interruption until it reconsolidates. During this period, reactivated memories can be altered (enhanced, impaired or otherwise updated) by behavioural or pharmacological manipulations. Animal studies suggest cortisol as possible modulator of reactivated memories, but its effects on human fear memory reconsolidation
44
R. Reynolds / Psychoneuroendocrinology 61 (2015) 1–78
are largely unknown, and are therefore the aim of the present study. Forty healthy males were assigned to one of three groups (Reactivation + Cortisol, Reactivation + Placebo, Cortisol + No-reactivation) and were tested on a three-day reconsolidation design. For fear acquisition, three geometrical shapes were used as conditioned stimuli (CS): two stimuli (CS1+, CS2+) were paired with an electrical shock; one stimulus (CS−) was never paired with a shock. On the second day, cortisol/placebo was administered prior to a single unreinforced presentation (memory reactivation) of CS1+, one of the previously reinforced CS+. On the third day, following extinction and reinstatement by shock, the return of fear to all stimuli was tested. Our results revealed a more pronounced reinstatement of the CS1+ in the Reactivation + Cortisol group, suggesting an enhancing effect of cortisol on the reactivated fear memory. The effect was highly specific to the reactivated CS1+ and did not affect the nonreactivated CS2+. The findings indicate a similarity between the processes mediating initial consolidation and reconsolidation following reactivation. These findings will be compared to the results of currently ongoing reconsolidation studies from our lab. Possible theoretical and clinical implications will be discussed. http://dx.doi.org/10.1016/j.psyneuen.2015.07.508
PO61 Fear conditioning, social groups and stress Christian Merz 1,2,∗ , Oliver Wolf 2 1 2
University Trier, Trier, Germany Ruhr Unvierstiy Bochum, Bochum, Germany
The stress hormone cortisol has been shown to reduce retrieval of fear- memories. Repeated pairings with an aversive unconditioned stimulus (UCS) with a neutral stimulus lead to the acquisition of fear-related properties of this now conditioned stimulus (CS+). Previously, it has been shown that in- and outgroup faces used as conditioned stimuli in a fear conditioning design evoke distinct response patterns. In this study, we investigated how acute stress intervenes with this social fear conditioning design. In the acquisition phase, 33 healthy men were confronted repeatedly with two in-group and two outgroup faces, one of each was paired with an electrical stimulation (UCS), representing the CS+, whereas the other was not coupled to the UCS (CS−). In the extinction phase, all CS were presented again but with no UCS application. On the next day, participants were randomly assigned to a stress or control condition. We tested for different extinction retrieval of in- and outgroup CS during increasing cortisol concentrations after stress induction (socially evaluated cold pressor test). Indeed, acute stress modulated extinction retrieval on the second day: whereas the control group showed a differentiation in skin conductance responses between in- and outgroup faces, stress abolished this differentiation. Overall, we could demonstrate that acute stress inhibits the retrieval of combined socially and fear-relevant information. Assumedly, the influence of stress hormones on the hippocampus is responsible for these effects given its role in fear retrieval, binding and context processing. http://dx.doi.org/10.1016/j.psyneuen.2015.07.509
PO62 Does stimulation of the mineralocorticoid receptor influence autobiographic memory retrieval? A study in patients with major depression, patients with borderline personality disorder and healthy controls Juliane Fleischer ∗ , Katja Wingenfeld, Linn Kühl, Kim Hinkelmann, Stefan Roepke, Christian Otte Charité Universitätsmedizin, Berlin, Germany There is evidence that stimulation of mineralocorticoid receptors (MR) enhances memory in healthy subjects and in patients with major depression (MDD). In contrast, in patients with borderline personality disorder (BPD) this effect seems to be taskdependent. Aim of this study was to investigate the effect of MR stimulation on autobiographic memory retrieval in healthy individuals, patients with MDD, and patients with BPD. We conducted a placebo-controlled study in an intra-individual cross-over design. Twenty-four patients with MDD, 37 patients with BPD and 67 healthy participants completed an autobiographic memory test after receiving 0.4 mg fludrocortisone, a mineralocorticoid receptor agonist, or placebo in a randomized order. Healthy subjects, patients with MDD, and patients with BPD did not differ in their autobiographic memory retrieval. Furthermore, the administration of fludrocortisone had no effect on autobiographic memory. In conclusion, the stimulation of MR does not influence autobiographic memory retrieval in healthy subjects, patients with MDD, and patients with BPD. Our results do not support a role of MR in autobiographic memory. http://dx.doi.org/10.1016/j.psyneuen.2015.07.510
PO63 Psychosocial stress affects attentional control and neural oscillatory activity Ismael Palacios-Garcia 1,∗ , Mario Villena-Gonzalez 1 , German Campos-Arteaga 1 , Claudio Artigas 1 , Karina Jaramillo 2 , Jaime Silva 2 , Eugenio Rodriguez 1 1
Pontificia Universidad Católica de Chile, Santiago, RM, Chile 2 Universidad del Desarollo, Santiago, RM, Chile Every day we have to divide our limited attentional resources into different external and internal demands. Considering that psychosocial stress promotes the allocation of attentional resources to threat-related stimuli such as the social evaluation, the aim of the study is (1) to investigate if psychosocial stress affects the behavioral performance in an attentional shifting task and (2) to search, under an exploratory approach, some of its neural correlates. 40 healthy participants were exposed to either an electroencephalogram-compatible version of the Trier Social Stress Test (TSST) or a control protocol. Additionally, immediately before and after these protocols, subject participated in the attentional shifting task. Manipulation checks were verified through the changes of the heart rate, salivary concentration of cortisol and the score in the anxiety scale in the “stress” condition respect the control. When we compared the behavioral performance in the attentional task prior and after both conditions, we found that the control group showed a clear improvement in performance, characterized by a relative increase of correct trials and