- Email: [email protected]
Consolidation and alteration of memories for stressful experiences in humans
Abstracts / Psychoneuroendocrinology 83S (2017) 1–89
Breastfeeding – Some regulating factors and some consequences Wibke Jonas 1,2,6,∗ , Rossana Bisceglia 2 , Viara Mileva 2 , Aya Dundin 2 , James Kennedy 3 , Michael Meaney 4 , Leslie Atkinson 5 , Meir Steiner 6 , Ashley Wazana 7 , Alison Fleming 2 1
Department of Women’s and Children’s Health, Karolinska Institutet, Sweden 2 Department of Psychology, University of Toronto, ON, Canada 3 Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada 4 Ludmer Centre for Neuroinformatics and Mental Health, Douglas Institute, McGill University, Montreal, QC, Canada 5 Ryerson University, Toronto, ON, Canada 6 Departments of Psychiatry & Behavioral Neurosciences and Obstetrics & Gynecology, McMaster University, Hamilton, ON, Canada 7 Department of Psychiatry, McGill University, Montreal, QC, Canada E-mail address: [email protected] (W. Jonas).
Background: Breastfeeding has positive documented effects on maternal and infant health. Aims: To better understand factors that regulate (1) breastfeeding by the mothers and (2) the “effects” of breastfeeding on the mother–infant dyad. Methods: Participants (n = 170) derive from the “Maternal Adversity, Vulnerability and Neurodevelopment study (MAVAN)”. Mothers provided data during pregnancy and first year postpartum on breastfeeding, early adversity (Childhood Trauma Questionnaire, CTQ), oxytocin gene and oxytocin gene receptor polymorphisms (OXT rs2740210, OXTR rs237885, OXT rs4813627), depression, anxiety (CES-D, STAI), infant temperament (Infant Behavioral Questionnaire) and maternal sensitivity (Ainsworth Sensitivity Scales). Mothers and infants provided cortisol samples. Results: We found an inverse relation between early adversity and duration of breastfeeding, which was mediated by maternal depression levels postpartum, but only in women carrying one variant of the oxytocin rs2740210 gene marker (CC genotype). That is, mothers who scored higher on the CTQ breastfeed longer if they carried the A allele and breastfeed for a shorter duration if they were homozygous for the C allele. Another moderated mediation analysis revealed that mothers who breastfeed at 3 months acted more sensitively towards their infants at 6 months and they in turn had infants who at 18 months showed reduced negative affectivity. This relationship was pronounced in women with higher anxiety. Maternal cortisol levels predicted infant cortisol levels, a relationship that was enhanced in breastfeeding mother–infant dyads. Conclusion: Our results help to clarify the interdependence between early life experiences, mood and breastfeeding in the mother–infant relationship, -physiology and in infant emotional development. http://dx.doi.org/10.1016/j.psyneuen.2017.07.418
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Symposium 16: Stress and emotional memories in humans: In search for neuroendocrine mechanisms and their neural correlates Time: Friday, 08/Sep/2017: 5:05 pm–6:35 pm Session Chair: Oliver T. Wolf, Katja Wingenfeld Opposing effects of cortisol on fear extinction and fear extinction recall: Evidence from two pharmacological fMRI studies Christian J. Merz 1,∗ , Valerie Kinner 1 , Andrea Hermann 2 , Oliver T. Wolf 1 1
Ruhr-University Bochum, Germany Justus Liebig University Giessen, Germany E-mail address: [email protected] (C.J. Merz). 2
Background: Stress hormones exert opposing effects on consolidation and retrieval processes in declarative memory: stress hormones facilitate consolidation, but impair retrieval. Whether these opposing influences also apply to the domain of fear extinction memory was explored in two pharmacological functional magnetic resonance imaging studies. Methods: During fear acquisition training, an electrical stimulation (unconditioned stimulus) was either paired with a neutral stimulus (conditioned stimulus, CS+) or not (CS−). Fear extinction training comprised presentations of both CS without further reinforcement. Fear extinction recall was tested at a separate test day again with presentations of both CS. In study one, cortisol (30 mg hydrocortisone) was given before extinction training. In study two, cortisol administration took place before extinction recall on the test day. Results: Study one revealed pre-extinction cortisol administration to enhance extinction learning as evident by reduced conditioned skin conductance responses (SCRs), diminished activation of the amygdala–hippocampal complex, and enhanced functional connectivity to the ventromedial prefrontal cortex (vmPFC). During extinction recall, the cortisol group exhibited increased hippocampal activation and connectivity to the vmPFC. Study two showed pre-recall cortisol administration to impair extinction recall characterized by increased SCRs and enhanced activation of the fear network in men. Conclusions: Both studies emphasize opposing effects of cortisol on fear extinction learning and extinction recall: on one side, cortisol enhanced consolidation of extinction memory, on the other side, cortisol impaired extinction memory recall by targeting relevant key nodes of the extinction network. Thus, cortisol can augment extinction-based psychotherapy while at the same time promoting relapses. http://dx.doi.org/10.1016/j.psyneuen.2017.07.419 Consolidation and alteration of memories for stressful experiences in humans Linda de Voogd Donders Institute, The Netherlands E-mail address: [email protected]. Background: Memories for stressful experiences are typically well remembered, not only due to immediate effects at encoding, but also through strengthening of subsequent consolidation processes following learning or memory reactivation. A large body of animal research shows how stress-sensitive hormones and neurotransmitters promote synaptic consolidation. However, memories are also reorganized in brain circuits at the systems level. Whether
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Abstracts / Psychoneuroendocrinology 83S (2017) 1–89
this reorganization is altered for memories for stressful experiences in humans is unclear. Methods: To investigate these offline systems-level interactions in humans, we performed a series of functional (connectivity) MRI studies including a learning phase and a subsequent resting-state period in which participants were instructed to remain awake. In a follow-up experiment we investigated whether we could interfere with these systems-level changes following memory reactivation. Results: We found that during post-learning rest, memories with a stressful connotation are spontaneously reactivated across hippocampal–neocortical circuits. We also found that additional to these state effects of stress on systems consolidation, systems-level interactions during rest as a trait characteristic play a role in the state effects of stress on strengthening memory. Finally, we showed that these systems-level interactions can be influenced after memory reactivation with an eyemovement intervention, thereby altering memory for such stressful experiences. Conclusions: In conclusion, stress-related arousal during learning promotes early systems-consolidation processes following learning and thereby strengthens memories for stressful experiences. Our findings reveal a systems-level mechanism that may explain the persistence of long-term memory for stressful experiences. Following memory reactivation, it is possible to interfere with this strengthening with a behavioral manipulation. http://dx.doi.org/10.1016/j.psyneuen.2017.07.420 Effects of increased noradrenergic activity by yohimbine on learning and extinction in patients with major depression Linn K. Kuehl ∗ , Christian E. Deuter, Christian Otte, Katja Wingenfeld Charité – Universitätsmedizin Berlin, Germany E-mail address: [email protected] (L.K. Kuehl). Background: Stress has been shown to play an important role in the development and maintenance of major depressive disorder (MDD). Furthermore, maladaptive changes in the physiological stress systems have been demonstrated. For instance, in the locus coeruleus-noradrenergic (LC-NA) system, an up-regulation of central alpha2-adrenergic receptors has been found. Chronic stress in early life, e.g. adverse childhood experiences (ACE) such as physical or sexual abuse, is one hypothesized mechanism. The LC-NA system influences the physiological stress response, but also cognitive function. Indeed, NA effects on cognitive functions such as learning and memory have been demonstrated in healthy individuals. Although cognitive deficits are core symptoms of MDD, the relationship of the LC-NA system and cognitive processes has rarely been investigated so far in these patients. Therefore, this study aims to investigate whether noradrenergic stimulation affects acquisition and extinction processes in MDD patients using a fear conditioning paradigm. Additionally, we aim to further disentangle the potentially mediating role of ACE. Methods: In a double-blind repeated measures design, 20 MDD patients with ACE, 20 MDD patients without ACE, 20 healthy participants with ACE and 20 healthy participants without ACE are tested after administration of 10 mg yohimbine or placebo. Results/conclusions: Results of this study will be presented at the conference. The results may contribute to a better understanding of the role of the LC-NA system – and potential consequences due to dysfunctional changes as a result of intense stress
experiences – as an underlying neurobiological mechanism of cognitive processes in MDD patients. http://dx.doi.org/10.1016/j.psyneuen.2017.07.421 Association between cortisol diurnal rhythm and emotional memory in healthy young volunteers Mitsue Nagamine 1,4,∗ , Hiroko Noguchi 2 , Nobuaki Takahashi 3 , Yoshiharu Kim 4 , Yutaka Matsuoka 5 1
Tokyo Institute of Technology, Japan Musashino University, Japan 3 Bukkyo University, Japan 4 National Center of Neurology and Psychiatry, Japan 5 National Cancer Center, Japan E-mail address: [email protected] (M. Nagamine). 2
Background: Few studies have investigated the relationship between cortisol diurnal rhythm and cognitive function in healthy young adults, especially for emotional memory. To address this deficiency, this study examined the effect of diurnal cortisol slope (DCS) and heart rate variability (HRV) on emotional memory. Methods: Participants included healthy volunteers (44 men and 23 women; mean age 20.60 yrs). Participants were shown emotionally arousing slides (learning day) and were asked to return to the laboratory one week later where they were given a “surprise” memory test to examine their emotional memory retention. Participants were asked to collect saliva samples at four time points (08:00, 11:00, 15:00, and 20:00) on the learning and retrieval days; these samples were used to calculate the diurnal cortisol slope variation. Moreover, HRV was measured during the experiment. Results: The multiple linear regression analysis revealed that declarative memory ability, sleep duration, and the DCS were the final significant determinants for emotional memory enhancement (B = −20.41, 0.08, −99.68, p = .02, .04, .05, respectively), with participants having flatter cortisol slopes showing reduced or absent emotional memory enhancement. Conclusions: These data suggest that cortisol diurnal rhythm can predict emotional memory enhancement. Participants with flatter diurnal cortisol rhythms showed a lower emotional memory enhancement for stimuli with a relatively low emotional arousal level. Thus, these findings demonstrate that cortisol is related to emotional memory consolidation both in circumstances of stress or pharmacological glucocorticoid treatment and in terms of diurnal rhythm. http://dx.doi.org/10.1016/j.psyneuen.2017.07.422
Breastfeeding – Some regulating factors and some consequences Wibke Jonas 1,2,6,∗ , Rossana Bisceglia 2 , Viara Mileva 2 , Aya Dundin 2 , James Kennedy 3 , Michael Meaney 4 , Leslie Atkinson 5 , Meir Steiner 6 , Ashley Wazana 7 , Alison Fleming 2 1
Department of Women’s and Children’s Health, Karolinska Institutet, Sweden 2 Department of Psychology, University of Toronto, ON, Canada 3 Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada 4 Ludmer Centre for Neuroinformatics and Mental Health, Douglas Institute, McGill University, Montreal, QC, Canada 5 Ryerson University, Toronto, ON, Canada 6 Departments of Psychiatry & Behavioral Neurosciences and Obstetrics & Gynecology, McMaster University, Hamilton, ON, Canada 7 Department of Psychiatry, McGill University, Montreal, QC, Canada E-mail address: [email protected] (W. Jonas).
Background: Breastfeeding has positive documented effects on maternal and infant health. Aims: To better understand factors that regulate (1) breastfeeding by the mothers and (2) the “effects” of breastfeeding on the mother–infant dyad. Methods: Participants (n = 170) derive from the “Maternal Adversity, Vulnerability and Neurodevelopment study (MAVAN)”. Mothers provided data during pregnancy and first year postpartum on breastfeeding, early adversity (Childhood Trauma Questionnaire, CTQ), oxytocin gene and oxytocin gene receptor polymorphisms (OXT rs2740210, OXTR rs237885, OXT rs4813627), depression, anxiety (CES-D, STAI), infant temperament (Infant Behavioral Questionnaire) and maternal sensitivity (Ainsworth Sensitivity Scales). Mothers and infants provided cortisol samples. Results: We found an inverse relation between early adversity and duration of breastfeeding, which was mediated by maternal depression levels postpartum, but only in women carrying one variant of the oxytocin rs2740210 gene marker (CC genotype). That is, mothers who scored higher on the CTQ breastfeed longer if they carried the A allele and breastfeed for a shorter duration if they were homozygous for the C allele. Another moderated mediation analysis revealed that mothers who breastfeed at 3 months acted more sensitively towards their infants at 6 months and they in turn had infants who at 18 months showed reduced negative affectivity. This relationship was pronounced in women with higher anxiety. Maternal cortisol levels predicted infant cortisol levels, a relationship that was enhanced in breastfeeding mother–infant dyads. Conclusion: Our results help to clarify the interdependence between early life experiences, mood and breastfeeding in the mother–infant relationship, -physiology and in infant emotional development. http://dx.doi.org/10.1016/j.psyneuen.2017.07.418
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Symposium 16: Stress and emotional memories in humans: In search for neuroendocrine mechanisms and their neural correlates Time: Friday, 08/Sep/2017: 5:05 pm–6:35 pm Session Chair: Oliver T. Wolf, Katja Wingenfeld Opposing effects of cortisol on fear extinction and fear extinction recall: Evidence from two pharmacological fMRI studies Christian J. Merz 1,∗ , Valerie Kinner 1 , Andrea Hermann 2 , Oliver T. Wolf 1 1
Ruhr-University Bochum, Germany Justus Liebig University Giessen, Germany E-mail address: [email protected] (C.J. Merz). 2
Background: Stress hormones exert opposing effects on consolidation and retrieval processes in declarative memory: stress hormones facilitate consolidation, but impair retrieval. Whether these opposing influences also apply to the domain of fear extinction memory was explored in two pharmacological functional magnetic resonance imaging studies. Methods: During fear acquisition training, an electrical stimulation (unconditioned stimulus) was either paired with a neutral stimulus (conditioned stimulus, CS+) or not (CS−). Fear extinction training comprised presentations of both CS without further reinforcement. Fear extinction recall was tested at a separate test day again with presentations of both CS. In study one, cortisol (30 mg hydrocortisone) was given before extinction training. In study two, cortisol administration took place before extinction recall on the test day. Results: Study one revealed pre-extinction cortisol administration to enhance extinction learning as evident by reduced conditioned skin conductance responses (SCRs), diminished activation of the amygdala–hippocampal complex, and enhanced functional connectivity to the ventromedial prefrontal cortex (vmPFC). During extinction recall, the cortisol group exhibited increased hippocampal activation and connectivity to the vmPFC. Study two showed pre-recall cortisol administration to impair extinction recall characterized by increased SCRs and enhanced activation of the fear network in men. Conclusions: Both studies emphasize opposing effects of cortisol on fear extinction learning and extinction recall: on one side, cortisol enhanced consolidation of extinction memory, on the other side, cortisol impaired extinction memory recall by targeting relevant key nodes of the extinction network. Thus, cortisol can augment extinction-based psychotherapy while at the same time promoting relapses. http://dx.doi.org/10.1016/j.psyneuen.2017.07.419 Consolidation and alteration of memories for stressful experiences in humans Linda de Voogd Donders Institute, The Netherlands E-mail address: [email protected]. Background: Memories for stressful experiences are typically well remembered, not only due to immediate effects at encoding, but also through strengthening of subsequent consolidation processes following learning or memory reactivation. A large body of animal research shows how stress-sensitive hormones and neurotransmitters promote synaptic consolidation. However, memories are also reorganized in brain circuits at the systems level. Whether
68
Abstracts / Psychoneuroendocrinology 83S (2017) 1–89
this reorganization is altered for memories for stressful experiences in humans is unclear. Methods: To investigate these offline systems-level interactions in humans, we performed a series of functional (connectivity) MRI studies including a learning phase and a subsequent resting-state period in which participants were instructed to remain awake. In a follow-up experiment we investigated whether we could interfere with these systems-level changes following memory reactivation. Results: We found that during post-learning rest, memories with a stressful connotation are spontaneously reactivated across hippocampal–neocortical circuits. We also found that additional to these state effects of stress on systems consolidation, systems-level interactions during rest as a trait characteristic play a role in the state effects of stress on strengthening memory. Finally, we showed that these systems-level interactions can be influenced after memory reactivation with an eyemovement intervention, thereby altering memory for such stressful experiences. Conclusions: In conclusion, stress-related arousal during learning promotes early systems-consolidation processes following learning and thereby strengthens memories for stressful experiences. Our findings reveal a systems-level mechanism that may explain the persistence of long-term memory for stressful experiences. Following memory reactivation, it is possible to interfere with this strengthening with a behavioral manipulation. http://dx.doi.org/10.1016/j.psyneuen.2017.07.420 Effects of increased noradrenergic activity by yohimbine on learning and extinction in patients with major depression Linn K. Kuehl ∗ , Christian E. Deuter, Christian Otte, Katja Wingenfeld Charité – Universitätsmedizin Berlin, Germany E-mail address: [email protected] (L.K. Kuehl). Background: Stress has been shown to play an important role in the development and maintenance of major depressive disorder (MDD). Furthermore, maladaptive changes in the physiological stress systems have been demonstrated. For instance, in the locus coeruleus-noradrenergic (LC-NA) system, an up-regulation of central alpha2-adrenergic receptors has been found. Chronic stress in early life, e.g. adverse childhood experiences (ACE) such as physical or sexual abuse, is one hypothesized mechanism. The LC-NA system influences the physiological stress response, but also cognitive function. Indeed, NA effects on cognitive functions such as learning and memory have been demonstrated in healthy individuals. Although cognitive deficits are core symptoms of MDD, the relationship of the LC-NA system and cognitive processes has rarely been investigated so far in these patients. Therefore, this study aims to investigate whether noradrenergic stimulation affects acquisition and extinction processes in MDD patients using a fear conditioning paradigm. Additionally, we aim to further disentangle the potentially mediating role of ACE. Methods: In a double-blind repeated measures design, 20 MDD patients with ACE, 20 MDD patients without ACE, 20 healthy participants with ACE and 20 healthy participants without ACE are tested after administration of 10 mg yohimbine or placebo. Results/conclusions: Results of this study will be presented at the conference. The results may contribute to a better understanding of the role of the LC-NA system – and potential consequences due to dysfunctional changes as a result of intense stress
experiences – as an underlying neurobiological mechanism of cognitive processes in MDD patients. http://dx.doi.org/10.1016/j.psyneuen.2017.07.421 Association between cortisol diurnal rhythm and emotional memory in healthy young volunteers Mitsue Nagamine 1,4,∗ , Hiroko Noguchi 2 , Nobuaki Takahashi 3 , Yoshiharu Kim 4 , Yutaka Matsuoka 5 1
Tokyo Institute of Technology, Japan Musashino University, Japan 3 Bukkyo University, Japan 4 National Center of Neurology and Psychiatry, Japan 5 National Cancer Center, Japan E-mail address: [email protected] (M. Nagamine). 2
Background: Few studies have investigated the relationship between cortisol diurnal rhythm and cognitive function in healthy young adults, especially for emotional memory. To address this deficiency, this study examined the effect of diurnal cortisol slope (DCS) and heart rate variability (HRV) on emotional memory. Methods: Participants included healthy volunteers (44 men and 23 women; mean age 20.60 yrs). Participants were shown emotionally arousing slides (learning day) and were asked to return to the laboratory one week later where they were given a “surprise” memory test to examine their emotional memory retention. Participants were asked to collect saliva samples at four time points (08:00, 11:00, 15:00, and 20:00) on the learning and retrieval days; these samples were used to calculate the diurnal cortisol slope variation. Moreover, HRV was measured during the experiment. Results: The multiple linear regression analysis revealed that declarative memory ability, sleep duration, and the DCS were the final significant determinants for emotional memory enhancement (B = −20.41, 0.08, −99.68, p = .02, .04, .05, respectively), with participants having flatter cortisol slopes showing reduced or absent emotional memory enhancement. Conclusions: These data suggest that cortisol diurnal rhythm can predict emotional memory enhancement. Participants with flatter diurnal cortisol rhythms showed a lower emotional memory enhancement for stimuli with a relatively low emotional arousal level. Thus, these findings demonstrate that cortisol is related to emotional memory consolidation both in circumstances of stress or pharmacological glucocorticoid treatment and in terms of diurnal rhythm. http://dx.doi.org/10.1016/j.psyneuen.2017.07.422