- Email: [email protected]
Hair cortisol in caregivers and their patients receiving allogeneic stem cell transplants – A clinical trial application
Abstracts / Psychoneuroendocrinology 83S (2017) 1–89
and (4) assess chronic psychosocial stress in adulthood. Taken together, studies of hair cortisol in non-human primates and other mammalian species strongly support the validity of this measure as a biomarker of long-term HPA activity that is sensitive to a variety of major life stressors. http://dx.doi.org/10.1016/j.psyneuen.2017.07.245 Incorporation and elimination pathways of cortisol in hair: Experimental evidence concerning the role of cortisol in sweat and light exposure Juliane Graß 1,∗ , Robert Miller Miller 1 , Esther H.D. Carlitz 2 , Fabian Patrovsky 1 , Clemens Kirschbaum 1 , Tobias Stalder 3 1
TU Dresden, Germany University of Zurich, Switzerland 3 University of Siegen, Germany E-mail address: [email protected] (J. Graß). 2
Background: Cumulative evidence supports the overall validity of cortisol analysis in human scalp hair. However, basic methodological aspects, such as pathways by which cortisol is incorporated into hair or eliminated from it, are still poorly understood. Specifically, potential acute and/or chronic effects associated with an incorporation of cortisol from sweat and/or an elimination of cortisol due to (UV)light exposure remain unknown. Methods: Here, we present data from a series of in vitro and in vivo experimental studies in which we carefully investigated potential influences of sweat exposure as well as (UV)light exposure on hair cortisol levels. Results: Our findings first corroborate previous evidence that considerable concentrations of cortisol are present in sweat. While data from in vitro experiments on already cut hair suggest that sweat cortisol can be incorporated into the hair shaft, in vivo findings on the effects of sweat-inducing interventions suggest no significant influence on hair cortisol levels under acute physiological conditions. Concerning the influence of (UV)light exposure, our findings consistently suggest that longer light exposure leads to a decrease of cortisol concentrations in hair. Conclusion: Our findings extend current knowledge on relevant methodological factors for hair cortisol analysis. Specifically, we find that experimentally exposing hair strands to (UV)light leads to a dose-dependent reduction of cortisol concentrations. This has clear implications on the storage of hair samples. Future research will be needed to further evaluate the impact of this effect under real-life conditions. http://dx.doi.org/10.1016/j.psyneuen.2017.07.246
3
Large-scale studies on the relationships between hair corticosteroids and depression, anxiety and cardiometabolic diseases in humans Elisabeth F.C. van Rossum 1,∗ , Sabine M. Staufenbiel 1 , Vincent L. Wester 1 , Gerard Noppe 1 , Jenny A. Visser 1 , Brenda W.J.H. Penninx 2 , Lotte Gerritsen 2 , Vincent W. Jaddoe 1 , Bert van Hemert 3 , Erica L.T. van den Akker 1 , Yolanda B. de Rijke 1 1
Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands 2 VU University Medical Center, Amsterdam, The Netherlands 3 Leiden University Medical Center, Leiden, The Netherlands E-mail address: [email protected] (E.F.C. van Rossum).
Background: In pathological conditions (e.g. Cushing’s disease) high cortisol levels cause mental disturbances as anxiety and depression, as well abdominal obesity and adverse cardiometabolic sequelae. It has been unclear how long-term measures of cortisol and cortisone are related to common psychiatric and cardiometabolic disorders. Methods: We used a well-validated LC-MS/MS based method to measure cortisol and cortisone content in 3 cm hair samples of: (1) 1166 participants of the Netherlands Study of Depression and Anxiety (NESDA), with 266 participants having a recent diagnosis of depressive and/or anxiety disorder, 655 having remitted disorders, and 245 healthy controls, and (2) 3019 children participating in the populationbased GenerationR study. Results: Presence of a comorbid depressive and anxiety disorder was associated with increased hair cortisol levels (p = .031), as was the severity of depressive (p = .029) and anxiety symptoms (p = .069). Remitted disorders were not associated with altered cortisol (study 1). Hair cortisol and cortisone were significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3–26.9) and OR: 1.9 (1.0–3.5), respectively). Both corticosteroids were significantly positively associated with body mass index, and (abdominal) fat mass (study 2). Conclusions: Persons with current severe symptoms of depression and/or anxiety, but not those with remitted symptoms, show higher levels of hair cortisol, indicating chronic overactivation of the HPA-axis. In addition, hair cortisol and cortisone concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy. http://dx.doi.org/10.1016/j.psyneuen.2017.07.247 Hair cortisol in caregivers and their patients receiving allogeneic stem cell transplants – A clinical trial application Mark L. Laudenslager University of Colorado Denver Anschutz Medical Campus, United States E-mail address: [email protected]. Background: Caregivers experience chronic and often uncontrollable stressors. Hair cortisol concentration (HCC) represents a promising marker of chronic activation of the hypothalamic pituitary adrenal axis and is applied with growing frequency in studies
4
Abstracts / Psychoneuroendocrinology 83S (2017) 1–89
of chronic distress. We hypothesized that HCC might register the impact of interventions that mitigate distress. We tested the feasibility of assessing HCC of caregivers and their cancer patients during a complex longitudinal study. Methods: 159 caregivers and their patients were followed for 6 months. We randomized caregivers to treatment as usual or a stress intervention and collected hair from caregivers every 3 months beginning at transplant for six months. We tracked practicality, acceptability, and outcomes of longitudinal hair collection. Results: Caregivers were more likely to provide samples at baseline (95%) but declined to 73% 6 months later. Fewer patients provided hair (59%) at transplant and at 6 months (47%). At transplant, 3 and 6 months. post-transplant, caregiver HCC was 26.6, 26.6, and 23.1 mg/pg respectively. Patient HCC at transplant and 6 mo. was 131.4 and 294.3, respectively, reflecting administration of steroids during treatment. Caregivers showed high stress, anxiety, and depressive symptoms, which were unrelated to natural log transformed HCC (lgnHCC). However, caregiver lgnHCC at 3 mo. correlated significantly with patient’s quality of life (r = −0.392). Discussion/Conclusions: The complexity of collecting hair during a clinical trial will be discussed as well as raise issues that arise with regard to unique cultural settings. (Supported in part by Patient Centered Outcomes Research Institute CE1304-6208; American Heart Association 15SFDRN24180024)
Methods: Internationally adopted children aged under 7 years arriving through Finnish adoption organizations between 2012 and 2016 were recruited to the on-going FinAdo follow-up study. HCC samples of 88 children (58% boys) were available. The control group (n = 92, 67% boys) was recruited from Finnish day-care centers. Background and health was studied with questionnaires. HCC was sampled 3 months after the arrival. The effects studied on HCC were the ages at adoption, at sampling, gender, continent of birth, type of placement before adoption, health status and reactive attachment disorder symptoms. Results: The mean age of the adopted children at sampling was 3.3 (SD 1.7) years and that of the control children 4.6 (1.4) years. The adoptees came from Asia 51%, Africa 37%, Eastern Europe 10% and America 2%, 82% of them from orphanages. Half of the children were healthy, 28% had structural defects and 25% other diseases. HCC (geometric mean) in the adoptees was 99.5 pg/mg (95%CI 62.9–157.2) and in the controls 23.8 pg/mg (95%CI 16.5–34.5), (p < 0.001). The difference sustained when controlled for the gender and age at sampling (p = 0.033). The older the child the lower the HCC was (r = −0.27, p < 0.001). Conclusion: Our results suggest that international adoptees especially the youngest ones suffer from stress indicated by HCC.
http://dx.doi.org/10.1016/j.psyneuen.2017.07.248
Symposium 3: Epigenetic mechanisms underlying early life adversity leading to long-lasting behavioral responses Time: Thursday, 07/Sep/2017: 2:00 pm–3:30 pm Session Chair: Noam Meiri, Aron Weller
Hair cortisol concentration as a stress marker in internationally adopted children – Preliminary results from the Finnish Adoption (FinAdo) Study Helena Leila Lapinleimu 1,2,∗ , Krista Liskola 3,4 , Hanna Raaska 4 , Jouni Lapinleimu 5,6 , Anna-Riitta Heikkilä 7,8 , Hanni Rönnlund 1,9 , Marko Elovainio 10,11 1
Department of Pediatrics and Adolescent Medicine, University of Turku, Turku, Finland 2 Department of Pediatrics and Adolescent Medicine, University Hospital of Turku, Turku, Finland 3 Department of Child Psychiatry, University of Helsinki, Helsinki, Finland 4 Department of Child Psychiatry, University Hospital of Helsinki, Helsinki, Finland 5 Department of Internal Medicine, University of Turku, Turku, Finland 6 Division of Medicine, Turku University Hospital, Salo Hospital, Finland 7 Department of Pediatrics and Adolescent Medicine, University of Helsinki, Helsinki, Finland 8 Department of Pediatrics and Adolescent Medicine, University Hospital of Helsinki, Helsinki, Finland 9 Health Care Center of Kaarina, Kaarina, Finland 10 Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland 11 National Institute for Health and Welfare, Helsinki, Finland E-mail address: lehela@utu.fi (H.L. Lapinleimu). Background: Internationally adopted children may have been maltreated or lived with inadequate care causing them psychological stress. The aim was to study hair cortisol concentrations (HCC) as a marker of long-term experienced stress and to find the potential correlates of HCC.
http://dx.doi.org/10.1016/j.psyneuen.2017.07.249
Transgenerational effects of early life trauma: Epigenetic mechanisms involving the germline Isabelle M. Mansuy UZH/ETHZ, Switzerland E-mail address: [email protected]. Behavior in mammals is strongly influenced by environmental factors, particularly when experienced during early postnatal life. While positive factors can favor proper behavioral responses, negative factors such as traumatic events can alter behavior and induce diseases like borderline personality disorder, bipolar depression and antisocial behaviors. Such disorders are usually marked in individuals directly exposed but strikingly, they can also affect their offspring sometimes across several generations. The biological mechanisms underlying the transmission of trauma-induced symptoms from parent to offspring have recently started to be examined and are thought to involve non-genetic factors. This talk will present an experimental model of early traumatic stress in mice and show evidence that non-genetic mechanisms are implicated in the expression and inheritance of the impact of such trauma. This mouse model exhibits altered social behaviors, depressive-like symptoms, cognitive deficits, and impaired glucose regulation in adulthood. The symptoms are pronounced and persist throughout life, and are further transmitted to the following offspring across several generations, through both females and males. They are associated with epigenetic alterations involving persistent changes in DNA methylation at the promoter-associated CpG island of several genes, in the brain of the offspring and the germline of their father. Further to DNA methylation, other nongenetic mechanisms involving regulation by non-coding RNAs and histone posttranslational modifications are also involved. These findings suggest that non-genetic processes largely contribute to
and (4) assess chronic psychosocial stress in adulthood. Taken together, studies of hair cortisol in non-human primates and other mammalian species strongly support the validity of this measure as a biomarker of long-term HPA activity that is sensitive to a variety of major life stressors. http://dx.doi.org/10.1016/j.psyneuen.2017.07.245 Incorporation and elimination pathways of cortisol in hair: Experimental evidence concerning the role of cortisol in sweat and light exposure Juliane Graß 1,∗ , Robert Miller Miller 1 , Esther H.D. Carlitz 2 , Fabian Patrovsky 1 , Clemens Kirschbaum 1 , Tobias Stalder 3 1
TU Dresden, Germany University of Zurich, Switzerland 3 University of Siegen, Germany E-mail address: [email protected] (J. Graß). 2
Background: Cumulative evidence supports the overall validity of cortisol analysis in human scalp hair. However, basic methodological aspects, such as pathways by which cortisol is incorporated into hair or eliminated from it, are still poorly understood. Specifically, potential acute and/or chronic effects associated with an incorporation of cortisol from sweat and/or an elimination of cortisol due to (UV)light exposure remain unknown. Methods: Here, we present data from a series of in vitro and in vivo experimental studies in which we carefully investigated potential influences of sweat exposure as well as (UV)light exposure on hair cortisol levels. Results: Our findings first corroborate previous evidence that considerable concentrations of cortisol are present in sweat. While data from in vitro experiments on already cut hair suggest that sweat cortisol can be incorporated into the hair shaft, in vivo findings on the effects of sweat-inducing interventions suggest no significant influence on hair cortisol levels under acute physiological conditions. Concerning the influence of (UV)light exposure, our findings consistently suggest that longer light exposure leads to a decrease of cortisol concentrations in hair. Conclusion: Our findings extend current knowledge on relevant methodological factors for hair cortisol analysis. Specifically, we find that experimentally exposing hair strands to (UV)light leads to a dose-dependent reduction of cortisol concentrations. This has clear implications on the storage of hair samples. Future research will be needed to further evaluate the impact of this effect under real-life conditions. http://dx.doi.org/10.1016/j.psyneuen.2017.07.246
3
Large-scale studies on the relationships between hair corticosteroids and depression, anxiety and cardiometabolic diseases in humans Elisabeth F.C. van Rossum 1,∗ , Sabine M. Staufenbiel 1 , Vincent L. Wester 1 , Gerard Noppe 1 , Jenny A. Visser 1 , Brenda W.J.H. Penninx 2 , Lotte Gerritsen 2 , Vincent W. Jaddoe 1 , Bert van Hemert 3 , Erica L.T. van den Akker 1 , Yolanda B. de Rijke 1 1
Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands 2 VU University Medical Center, Amsterdam, The Netherlands 3 Leiden University Medical Center, Leiden, The Netherlands E-mail address: [email protected] (E.F.C. van Rossum).
Background: In pathological conditions (e.g. Cushing’s disease) high cortisol levels cause mental disturbances as anxiety and depression, as well abdominal obesity and adverse cardiometabolic sequelae. It has been unclear how long-term measures of cortisol and cortisone are related to common psychiatric and cardiometabolic disorders. Methods: We used a well-validated LC-MS/MS based method to measure cortisol and cortisone content in 3 cm hair samples of: (1) 1166 participants of the Netherlands Study of Depression and Anxiety (NESDA), with 266 participants having a recent diagnosis of depressive and/or anxiety disorder, 655 having remitted disorders, and 245 healthy controls, and (2) 3019 children participating in the populationbased GenerationR study. Results: Presence of a comorbid depressive and anxiety disorder was associated with increased hair cortisol levels (p = .031), as was the severity of depressive (p = .029) and anxiety symptoms (p = .069). Remitted disorders were not associated with altered cortisol (study 1). Hair cortisol and cortisone were significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3–26.9) and OR: 1.9 (1.0–3.5), respectively). Both corticosteroids were significantly positively associated with body mass index, and (abdominal) fat mass (study 2). Conclusions: Persons with current severe symptoms of depression and/or anxiety, but not those with remitted symptoms, show higher levels of hair cortisol, indicating chronic overactivation of the HPA-axis. In addition, hair cortisol and cortisone concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy. http://dx.doi.org/10.1016/j.psyneuen.2017.07.247 Hair cortisol in caregivers and their patients receiving allogeneic stem cell transplants – A clinical trial application Mark L. Laudenslager University of Colorado Denver Anschutz Medical Campus, United States E-mail address: [email protected]. Background: Caregivers experience chronic and often uncontrollable stressors. Hair cortisol concentration (HCC) represents a promising marker of chronic activation of the hypothalamic pituitary adrenal axis and is applied with growing frequency in studies
4
Abstracts / Psychoneuroendocrinology 83S (2017) 1–89
of chronic distress. We hypothesized that HCC might register the impact of interventions that mitigate distress. We tested the feasibility of assessing HCC of caregivers and their cancer patients during a complex longitudinal study. Methods: 159 caregivers and their patients were followed for 6 months. We randomized caregivers to treatment as usual or a stress intervention and collected hair from caregivers every 3 months beginning at transplant for six months. We tracked practicality, acceptability, and outcomes of longitudinal hair collection. Results: Caregivers were more likely to provide samples at baseline (95%) but declined to 73% 6 months later. Fewer patients provided hair (59%) at transplant and at 6 months (47%). At transplant, 3 and 6 months. post-transplant, caregiver HCC was 26.6, 26.6, and 23.1 mg/pg respectively. Patient HCC at transplant and 6 mo. was 131.4 and 294.3, respectively, reflecting administration of steroids during treatment. Caregivers showed high stress, anxiety, and depressive symptoms, which were unrelated to natural log transformed HCC (lgnHCC). However, caregiver lgnHCC at 3 mo. correlated significantly with patient’s quality of life (r = −0.392). Discussion/Conclusions: The complexity of collecting hair during a clinical trial will be discussed as well as raise issues that arise with regard to unique cultural settings. (Supported in part by Patient Centered Outcomes Research Institute CE1304-6208; American Heart Association 15SFDRN24180024)
Methods: Internationally adopted children aged under 7 years arriving through Finnish adoption organizations between 2012 and 2016 were recruited to the on-going FinAdo follow-up study. HCC samples of 88 children (58% boys) were available. The control group (n = 92, 67% boys) was recruited from Finnish day-care centers. Background and health was studied with questionnaires. HCC was sampled 3 months after the arrival. The effects studied on HCC were the ages at adoption, at sampling, gender, continent of birth, type of placement before adoption, health status and reactive attachment disorder symptoms. Results: The mean age of the adopted children at sampling was 3.3 (SD 1.7) years and that of the control children 4.6 (1.4) years. The adoptees came from Asia 51%, Africa 37%, Eastern Europe 10% and America 2%, 82% of them from orphanages. Half of the children were healthy, 28% had structural defects and 25% other diseases. HCC (geometric mean) in the adoptees was 99.5 pg/mg (95%CI 62.9–157.2) and in the controls 23.8 pg/mg (95%CI 16.5–34.5), (p < 0.001). The difference sustained when controlled for the gender and age at sampling (p = 0.033). The older the child the lower the HCC was (r = −0.27, p < 0.001). Conclusion: Our results suggest that international adoptees especially the youngest ones suffer from stress indicated by HCC.
http://dx.doi.org/10.1016/j.psyneuen.2017.07.248
Symposium 3: Epigenetic mechanisms underlying early life adversity leading to long-lasting behavioral responses Time: Thursday, 07/Sep/2017: 2:00 pm–3:30 pm Session Chair: Noam Meiri, Aron Weller
Hair cortisol concentration as a stress marker in internationally adopted children – Preliminary results from the Finnish Adoption (FinAdo) Study Helena Leila Lapinleimu 1,2,∗ , Krista Liskola 3,4 , Hanna Raaska 4 , Jouni Lapinleimu 5,6 , Anna-Riitta Heikkilä 7,8 , Hanni Rönnlund 1,9 , Marko Elovainio 10,11 1
Department of Pediatrics and Adolescent Medicine, University of Turku, Turku, Finland 2 Department of Pediatrics and Adolescent Medicine, University Hospital of Turku, Turku, Finland 3 Department of Child Psychiatry, University of Helsinki, Helsinki, Finland 4 Department of Child Psychiatry, University Hospital of Helsinki, Helsinki, Finland 5 Department of Internal Medicine, University of Turku, Turku, Finland 6 Division of Medicine, Turku University Hospital, Salo Hospital, Finland 7 Department of Pediatrics and Adolescent Medicine, University of Helsinki, Helsinki, Finland 8 Department of Pediatrics and Adolescent Medicine, University Hospital of Helsinki, Helsinki, Finland 9 Health Care Center of Kaarina, Kaarina, Finland 10 Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland 11 National Institute for Health and Welfare, Helsinki, Finland E-mail address: lehela@utu.fi (H.L. Lapinleimu). Background: Internationally adopted children may have been maltreated or lived with inadequate care causing them psychological stress. The aim was to study hair cortisol concentrations (HCC) as a marker of long-term experienced stress and to find the potential correlates of HCC.
http://dx.doi.org/10.1016/j.psyneuen.2017.07.249
Transgenerational effects of early life trauma: Epigenetic mechanisms involving the germline Isabelle M. Mansuy UZH/ETHZ, Switzerland E-mail address: [email protected]. Behavior in mammals is strongly influenced by environmental factors, particularly when experienced during early postnatal life. While positive factors can favor proper behavioral responses, negative factors such as traumatic events can alter behavior and induce diseases like borderline personality disorder, bipolar depression and antisocial behaviors. Such disorders are usually marked in individuals directly exposed but strikingly, they can also affect their offspring sometimes across several generations. The biological mechanisms underlying the transmission of trauma-induced symptoms from parent to offspring have recently started to be examined and are thought to involve non-genetic factors. This talk will present an experimental model of early traumatic stress in mice and show evidence that non-genetic mechanisms are implicated in the expression and inheritance of the impact of such trauma. This mouse model exhibits altered social behaviors, depressive-like symptoms, cognitive deficits, and impaired glucose regulation in adulthood. The symptoms are pronounced and persist throughout life, and are further transmitted to the following offspring across several generations, through both females and males. They are associated with epigenetic alterations involving persistent changes in DNA methylation at the promoter-associated CpG island of several genes, in the brain of the offspring and the germline of their father. Further to DNA methylation, other nongenetic mechanisms involving regulation by non-coding RNAs and histone posttranslational modifications are also involved. These findings suggest that non-genetic processes largely contribute to