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Williams KC, Nto NJ, van Vuren EJ, Sallie FN, Molebatsi K, Kroneberg KS, Roomaney AA, Salie M, Womersley JS. Early biological and psychosocial factors associated with PTSD onset and persistence in youth. Eur J Psychotraumatol 2024; 15:2432160. [PMID: 39648852 PMCID: PMC11632931 DOI: 10.1080/20008066.2024.2432160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 10/28/2024] [Accepted: 10/29/2024] [Indexed: 12/10/2024] Open
Abstract
Background: Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that can develop after experiencing or witnessing a traumatic event. While considerable research has investigated PTSD in adults, little is known about the biological, psychological, and social factors that contribute to its onset, development, and persistence in youth.Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify longitudinal studies examining factors associated with PTSD status and symptom severity in children and adolescents. Literature searches were conducted in PubMed, Scopus, and Web of Science, yielding 24 eligible studies after screening.Results: The included studies identified various biological factors associated with paediatric PTSD, including dysregulation of the hypothalamic-pituitary-adrenal axis, brain structural alterations, and physiological markers such as heart rate. Psychological factors, including depression, trauma appraisals, coping styles, and cognitive deficits predicted PTSD symptom development. Social factors included parental PTSD, family environment, and cultural influences. Many studies highlighted the importance of the interplay between these biological, psychological, and social factors in the manifestation of PTSD in youth.Conclusion: This review synthesises evidence that PTSD development in youth is influenced by a complex array of neurobiological vulnerabilities, psychological processes, and environmental factors. Longitudinal, multi-dimensional studies are needed to further elucidate personalised risk profiles and trajectories, which can inform targeted prevention and intervention strategies for PTSD in youth.
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Affiliation(s)
- Kimberley C. Williams
- Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- Neuroscience Institute, University of Cape Town, Cape Town, South Africa
| | - Nto J. Nto
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Extramural Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Department of Anatomy, Faculty of Basic Medical Sciences, University of Nigeria, Nsukka, Nigeria
| | - Esmé Jansen van Vuren
- Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa
- SAMRC Extramural Unit for Hypertension and Cardiovascular Disease, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa
| | - Farhanah N. Sallie
- Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa
- School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa
| | - Keneilwe Molebatsi
- Department of Psychiatry, Faculty of Medicine, University of Botswana, Gaborone, Botswana
| | - Kayla S. Kroneberg
- Western Cape Department of Health, False Bay District Hospital, Cape Town, South Africa
| | - Aqeedah A. Roomaney
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Extramural Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Muneeb Salie
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Jacqueline S. Womersley
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Extramural Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Sharp TH, Chideya Y, Giuliani A, Hunt X, Tomlinson M, Seedat S, Creswell C, Fearon P, Hamilton-Giachritsis C, Hiller R, Meiser-Stedman R, Du Toit S, Stewart J, Halligan SL. Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study. BMJ Open 2024; 14:e085129. [PMID: 38991675 PMCID: PMC11624694 DOI: 10.1136/bmjopen-2024-085129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 06/05/2024] [Indexed: 07/13/2024] Open
Abstract
INTRODUCTION Children exposed to trauma are vulnerable to developing post-traumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high-income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities. METHODS AND ANALYSIS We will conduct a longitudinal, observational study of 250 children aged 8-16 years and their caregivers in South Africa, following child exposure to acute trauma. Dyads will be recruited from community hospitals following a potentially traumatic event, such as a motor vehicle accident or assault. Potential participants will be identified during their hospital visit, and if they agree, will subsequently be contacted by study researchers. Assessments will take place within 4 weeks of the traumatic event, with 3-month and 6-month follow-up assessments. Participants will provide a narrative description of the traumatic event and complete questionnaires designed to give information about social and psychological risk factors. Child PTSD symptoms will be the primary outcome, and wider trauma-related mental health (depression, anxiety, behavioural problems) will be secondary outcomes. Regression-based methods will be used to examine the association of psychosocial factors in the acute phase following trauma, including caregiver support and responding, with child PTSD and wider mental health outcomes. ETHICS AND DISSEMINATION Ethical approvals have been granted by Stellenbosch University and the University of Bath, with additional approvals to recruit via hospitals and healthcare clinics being granted by the University of Cape Town, the Department of Health and the City of Cape Town. Study findings will be disseminated via publication in journals, workshops for practitioners and policy-makers, and public engagement events.
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Affiliation(s)
| | - Yeukai Chideya
- Institute for Life Course Health Research, Department of Global Health, Stellenbosch University, Stellenbosch, South Africa
| | | | - Xanthe Hunt
- Institute for Life Course Health Research, Department of Global Health, Stellenbosch University, Stellenbosch, South Africa
| | - Mark Tomlinson
- Institute for Life Course Health Research, Department of Global Health, Stellenbosch University, Stellenbosch, South Africa
- School of Nursing and Midwifery, Queen's University Belfast, Belfast, UK
| | - Soraya Seedat
- Department of Psychiatry, Stellenbosch University, Stellenbosch, Western Cape, South Africa
- Department of Psychology, Stellenbosch University, Stellenbosch, Western Cape, South Africa
| | - Cathy Creswell
- Department of Experimental Psychology, University of Oxford, Oxford, UK
| | - Pasco Fearon
- University of Cambridge Centre for Family Research, Cambridge, UK
| | | | - Rachel Hiller
- Division of Psychology and Language Sciences, University College London, London, UK
| | - Richard Meiser-Stedman
- Department of Clinical Psychology and Psychological Therapies, University of East Anglia Norwich Medical School, Norwich, UK
| | - Stefani Du Toit
- Department of Psychiatry, University of Cape Town, Rondebosch, South Africa
| | - Jackie Stewart
- Department of Global Health, Stellenbosch University, Stellenbosch, South Africa
- Department of Surgery, University of Cape Town, Rondebosch, South Africa
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Bilodeau-Houle A, Raymond C, Marin MF. It's all in the hair: Association between changes in hair cortisol concentrations in reaction to the COVID-19 pandemic and post-traumatic stress symptoms in children over time. Psychoneuroendocrinology 2024; 164:107019. [PMID: 38518705 DOI: 10.1016/j.psyneuen.2024.107019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 01/26/2024] [Accepted: 03/07/2024] [Indexed: 03/24/2024]
Abstract
After exposure to a stressful/traumatic event, some individuals will develop post-traumatic stress symptoms (PTSS). In adults, low cortisol levels appear to be a risk factor for the development of PTSS. Indeed, both lower pre-trauma cortisol levels and low cortisol levels in the aftermath of a traumatic event have been associated with greater PTSS. In contrast, studies conducted in children showed that elevated cortisol levels shortly after trauma exposure are associated with more severe post-traumatic stress symptomatology. The few studies that have examined how pre-trauma cortisol levels predict PTSS in children have found no effect. Given that a pandemic can induce PTSS in certain individuals, we investigated whether cortisol secretion prior to and in the early stages of the COVID-19 pandemic in Quebec (Canada) predicted PTSS in children. In June 2020, we collected a hair sample from 71 children (8-15 y/o, M = 11.65; 54.93% girls) without a history of psychopathology or exposure to previous traumatic events. Hair samples allowed us to derive cumulative measures of cortisol levels for the months prior to (from mid-December 2019 to mid-March 2020) and at the beginning of the pandemic (from mid-March 2020 to mid-June 2020). PTSS were assessed every 3 months between June 2020 (T1) and March 2021 (T4). The results showed that a greater increase in hair cortisol at the beginning of the pandemic predicted less PTSS at T1, with an increase in these symptoms over time. This study highlights the utility of using hair cortisol during future chronic stressful events to better understand its association with the evolution of distress.
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Affiliation(s)
- Alexe Bilodeau-Houle
- Department of Psychology, Université du Québec à Montréal, Montreal, Quebec H2X 3P2, Canada; Research Center of the Institut universitaire en santé mentale de Montréal, Montreal, Quebec H1N 3V2, Canada
| | - Catherine Raymond
- Department of Psychology, Université du Québec à Montréal, Montreal, Quebec H2X 3P2, Canada; Research Center of the Institut universitaire en santé mentale de Montréal, Montreal, Quebec H1N 3V2, Canada
| | - Marie-France Marin
- Department of Psychology, Université du Québec à Montréal, Montreal, Quebec H2X 3P2, Canada; Research Center of the Institut universitaire en santé mentale de Montréal, Montreal, Quebec H1N 3V2, Canada.
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Chau AN, Eckberg RA, Laksana E, Ehrlich L, Ledbetter DR, Aczon MD, Gold JI, Wetzel RC, Nelson LP. Prehospitalization Trauma and Physiologic Factors Associated with the Presence of Post-traumatic Stress 3 Months After PICU Discharge. J Intensive Care Med 2024; 39:268-276. [PMID: 38105524 DOI: 10.1177/08850666231201786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2023]
Abstract
BACKGROUND Children admitted to the pediatric intensive care unit (PICU) have post-traumatic stress (PTS) rates up to 64%, and up to 28% of them meet criteria for PTS disorder (PTSD). We aim to examine whether a prior trauma history and increased physiologic parameters due to a heightened sympathetic response are associated with later PTS. Our hypothesis was children with history of prehospitalization trauma, higher heart rates, blood pressures, cortisol, and extrinsic catecholamine administration during PICU admission are more likely to have PTS after discharge. METHODS This is a prospective, observational study of children admitted to the PICU at an urban, quaternary, academic children's hospital. Children aged 8 to 17 years old without developmental delay, severe psychiatric disorder, or traumatic brain injury were included. Children's prehospitalization trauma history was assessed with a semistructured interview. All in-hospital variables were from the electronic medical record. PTS was present if children had 4 of the Diagnostic and Statistical Manual of Mental Disorders IV criteria for PTSD. Student's t- and chi-squared tests were used to compare the presence or absence of prior trauma and all of the PICU-associated variables. RESULTS Of the 110 children at baseline, 67 had 3-month follow-up. In the latter group, 46% met the criteria for PTS, mean age of 13 years (SD 3), 57% male, a mean PRISM III score of 4.9 (SD 4.3), and intensive care unit length of stay 6.5 days (SD 7.8). There were no statistically significant differences in the demographics of the children with and without PTS. The only variable to show significance was trauma history; children with prehospitalization trauma were more likely to have PTS at 3-month follow-up (P = .02). CONCLUSIONS Prehospitalization trauma history was associated with the presence of PTS after admission to the PICU. This study suggests future studies should shift to the potential predictive benefit of screening children for trauma history upon PICU admission.
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Affiliation(s)
- Ariya N Chau
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Ryan A Eckberg
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Laura P. and Leland K. Whittier Virtual Pediatric Intensive Care Unit, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Eugene Laksana
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Laura P. and Leland K. Whittier Virtual Pediatric Intensive Care Unit, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Lili Ehrlich
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Laura P. and Leland K. Whittier Virtual Pediatric Intensive Care Unit, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - David R Ledbetter
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Laura P. and Leland K. Whittier Virtual Pediatric Intensive Care Unit, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Melissa D Aczon
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Laura P. and Leland K. Whittier Virtual Pediatric Intensive Care Unit, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Jeffrey I Gold
- Department of Anesthesiology Critical Care Medicine, Division of Pain Medicine, University Center for Excellence in Developmental Disabilities, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Departments of Anesthesiology and Psychiatry & Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Randall C Wetzel
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Laura P. and Leland K. Whittier Virtual Pediatric Intensive Care Unit, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Lara P Nelson
- Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Department of Anesthesiology Critical Care Medicine, Division of Pain Medicine, University Center for Excellence in Developmental Disabilities, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA
- Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Azevedo M, Martinho R, Oliveira A, Correia-de-Sá P, Moreira-Rodrigues M. Molecular pathways underlying sympathetic autonomic overshooting leading to fear and traumatic memories: looking for alternative therapeutic options for post-traumatic stress disorder. Front Mol Neurosci 2024; 16:1332348. [PMID: 38260808 PMCID: PMC10800988 DOI: 10.3389/fnmol.2023.1332348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 12/12/2023] [Indexed: 01/24/2024] Open
Abstract
The sympathoadrenal medullary system and the hypothalamic-pituitary-adrenal axis are both activated upon stressful events. The release of catecholamines, such as dopamine, norepinephrine (NE), and epinephrine (EPI), from sympathetic autonomic nerves participate in the adaptive responses to acute stress. Most theories suggest that activation of peripheral β-adrenoceptors (β-ARs) mediates catecholamines-induced memory enhancement. These include direct activation of β-ARs in the vagus nerve, as well as indirect responses to catecholamine-induced glucose changes in the brain. Excessive sympathetic activity is deeply associated with memories experienced during strong emotional stressful conditions, with catecholamines playing relevant roles in fear and traumatic memories consolidation. Recent findings suggest that EPI is implicated in fear and traumatic contextual memories associated with post-traumatic stress disorder (PTSD) by increasing hippocampal gene transcription (e.g., Nr4a) downstream to cAMP response-element protein activation (CREB). Herein, we reviewed the literature focusing on the molecular mechanisms underlying the pathophysiology of memories associated with fear and traumatic experiences to pave new avenues for the treatment of stress and anxiety conditions, such as PTSD.
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Affiliation(s)
- Márcia Azevedo
- Laboratory of General Physiology, Department of Immuno-Physiology and Pharmacology and Center for Drug Discovery and Innovative Medicines (MedInUP), School of Medicine and Biomedical Sciences (ICBAS), University of Porto (UP), Porto, Portugal
| | - Raquel Martinho
- Laboratory of General Physiology, Department of Immuno-Physiology and Pharmacology and Center for Drug Discovery and Innovative Medicines (MedInUP), School of Medicine and Biomedical Sciences (ICBAS), University of Porto (UP), Porto, Portugal
| | - Ana Oliveira
- Laboratory of General Physiology, Department of Immuno-Physiology and Pharmacology and Center for Drug Discovery and Innovative Medicines (MedInUP), School of Medicine and Biomedical Sciences (ICBAS), University of Porto (UP), Porto, Portugal
| | - Paulo Correia-de-Sá
- Laboratory of Pharmacology and Neurobiology, Department of Immuno-Physiology and Pharmacology and Center for Drug Discovery and Innovative Medicines (MedInUP), School of Medicine and Biomedical Sciences (ICBAS), University of Porto (UP), Porto, Portugal
| | - Mónica Moreira-Rodrigues
- Laboratory of General Physiology, Department of Immuno-Physiology and Pharmacology and Center for Drug Discovery and Innovative Medicines (MedInUP), School of Medicine and Biomedical Sciences (ICBAS), University of Porto (UP), Porto, Portugal
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Monari S, Guillot de Suduiraut I, Grosse J, Zanoletti O, Walker SE, Mesquita M, Wood TC, Cash D, Astori S, Sandi C. Blunted Glucocorticoid Responsiveness to Stress Causes Behavioral and Biological Alterations That Lead to Posttraumatic Stress Disorder Vulnerability. Biol Psychiatry 2023:S0006-3223(23)01590-1. [PMID: 37743003 DOI: 10.1016/j.biopsych.2023.09.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/24/2023] [Accepted: 09/15/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND Understanding why only a subset of trauma-exposed individuals develop posttraumatic stress disorder is critical for advancing clinical strategies. A few behavioral (deficits in fear extinction) and biological (blunted glucocorticoid levels, small hippocampal size, and rapid-eye-movement sleep [REMS] disturbances) traits have been identified as potential vulnerability factors. However, whether and to what extent these traits are interrelated and whether one of them could causally engender the others are not known. METHODS In a genetically selected rat model of reduced corticosterone responsiveness to stress, we explored posttraumatic stress disorder-related biobehavioral traits using ex vivo magnetic resonance imaging, cued fear conditioning, and polysomnographic recordings combined with in vivo photometric measurements. RESULTS We showed that genetic selection for blunted glucocorticoid responsiveness led to a correlated multitrait response, including impaired fear extinction (observed in males but not in females), small hippocampal volume, and REMS disturbances, supporting their interrelatedness. Fear extinction deficits and concomitant disruptions in REMS could be normalized through postextinction corticosterone administration, causally implicating glucocorticoid deficiency in two core posttraumatic stress disorder-related risk factors and manifestations. Furthermore, reduced REMS was accompanied by higher norepinephrine levels in the hippocampal dentate gyrus that were also reversed by postextinction corticosterone treatment. CONCLUSIONS Our results indicate a predominant role for glucocorticoid deficiency over the contribution of reduced hippocampal volume in engendering both REMS alterations and associated deficits in fear extinction consolidation, and they causally implicate blunted glucocorticoids in sustaining neurophysiological disturbances that lead to fear extinction deficits.
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Affiliation(s)
- Silvia Monari
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Isabelle Guillot de Suduiraut
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Jocelyn Grosse
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Olivia Zanoletti
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Sophie E Walker
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - Michel Mesquita
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Tobias C Wood
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Diana Cash
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Simone Astori
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
| | - Carmen Sandi
- Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Synapsy Center for Neuroscience and Mental Health Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
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On making (and turning adaptive to) maladaptive aversive memories in laboratory rodents. Neurosci Biobehav Rev 2023; 147:105101. [PMID: 36804263 DOI: 10.1016/j.neubiorev.2023.105101] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/03/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023]
Abstract
Fear conditioning and avoidance tasks usually elicit adaptive aversive memories. Traumatic memories are more intense, generalized, inflexible, and resistant to attenuation via extinction- and reconsolidation-based strategies. Inducing and assessing these dysfunctional, maladaptive features in the laboratory are crucial to interrogating posttraumatic stress disorder's neurobiology and exploring innovative treatments. Here we analyze over 350 studies addressing this question in adult rats and mice. There is a growing interest in modeling several qualitative and quantitative memory changes by exposing already stressed animals to freezing- and avoidance-related tests or using a relatively high aversive training magnitude. Other options combine aversive/fearful tasks with post-acquisition or post-retrieval administration of one or more drugs provoking neurochemical or epigenetic alterations reported in the trauma aftermath. It is potentially instructive to integrate these procedures and incorporate the measurement of autonomic and endocrine parameters. Factors to consider when defining the organismic and procedural variables, partially neglected aspects (sex-dependent differences and recent vs. remote data comparison) and suggestions for future research (identifying reliable individual risk and treatment-response predictors) are discussed.
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Agoston AM. Expanding Neuroprotective Care: A Trauma-Informed Approach to Delivery of Services within Pediatric Inpatient Units. Clin Pediatr (Phila) 2023; 62:234-240. [PMID: 36039787 DOI: 10.1177/00099228221120290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Children with a history of trauma or adverse childhood experiences may be at higher risk for poor psychological and physical responses to medical experiences aimed at enhancing their well-being. Health care institutions are aware of the need for integration of trauma-informed care (TIC) practices yet struggle to find frameworks that promote resiliency to medical stress. An approach called neuroprotective care buffers the effects of toxic stress negatively affecting child health and well-being. Although often used in neonatal and cardiac intensive care units, the development and broad implementation of universal neuroprotective care measures across age groups and hospital settings has not been previously explored. An expanded neuroprotective care protocol takes a prevention approach to TIC. It fits a TIC framework, accounts for children's ecological, biological, and developmental needs, protects them against medical traumatic stress and retraumatization, and provides a tailored, measurable approach that systematically preserves child well-being within hospital settings.
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Affiliation(s)
- A Monica Agoston
- Children's Healthcare of Atlanta, Atlanta, GA, USA.,Division of Pediatric Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA
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Schmidt T, Meller S, Talbot SR, Packer RMA, Volk HA. Urinary neurotransmitter analysis and canine behavior assessment. Front Vet Sci 2023; 10:1124231. [PMID: 36814465 PMCID: PMC9939829 DOI: 10.3389/fvets.2023.1124231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 01/17/2023] [Indexed: 02/09/2023] Open
Abstract
Behavioral problems are highly prevalent in domestic dogs, negatively affecting the quality of life of dogs and their owners. In humans and dogs, neuropsychological or neurobehavioral disorders can be associated with deviations in various neurotransmitter systems. Previous evidence has revealed correlations between urinary neurotransmitters and various behavioral disorders; however, a causal relationship has not yet been conclusively demonstrated. Non-invasive urinary neurotransmitter analysis may identify specific biomarkers, which enable a more differentiated assessment of canine behavioral disorders in the future and contribute to more effective neuromodulatory treatment decisions and monitoring. This approach could offer new insights into underlying pathomechanisms of canine neurobehavioral disorders. This study assessed urinary neurotransmitter levels and the descriptive behavior profile of 100 dogs using established rating scales (Canine Behavioral Assessment and Research Questionnaire, Attention Deficit Hyperactivity Disorder Rating Scale, Dog Personality Questionnaire, Canine Cognitive Dysfunction Rating Scale), and explored relationships between these variables. No correlation was found between urinary neurotransmitters and the assessed behavior profiles; however, age-, sex- and neuter-related influences were identified. The lack of correlation could be explained by the many confounding factors influencing both behavior and urinary neurotransmitter excretion, including age, sex and neuter status effects, and methodological issues e.g., low discriminatory power between anxiety and aggression in the descriptive behavior evaluation. Urinary neurotransmitter testing could not be validated as a tool for canine behavior evaluation in this study. However, reliable assessment methods with low susceptibility to human biases could be valuable in the future to support behavioral-phenotype diagnoses.
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Affiliation(s)
- Teresa Schmidt
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
- Centre for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Sebastian Meller
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
| | - Steven Roger Talbot
- Hannover Medical School, Institute for Laboratory Animal Science, Hannover, Germany
| | - Rowena Mary Anne Packer
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Holger Andreas Volk
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
- Centre for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany
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Koirala R, Aass HCD, Søegaard EGI, Dhakal HP, Ojha SP, Hauff E, Thapa SB. Association of pro-inflammatory cytokines with trauma and post-traumatic stress disorder visiting a tertiary care hospital in Kathmandu. PLoS One 2023; 18:e0281125. [PMID: 36730263 PMCID: PMC9894492 DOI: 10.1371/journal.pone.0281125] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 01/15/2023] [Indexed: 02/03/2023] Open
Abstract
Post-traumatic stress disorder (PTSD) is a mental disorder that can occur after trauma. Although inflammatory markers such as cytokines are found altered in trauma and PTSD, there is no consensus regarding which can be considered as biomarkers. Studies from South Asia region is also rare. We studied cytokines among trauma affected patients and matched healthy controls. Fifty patients (cases) with trauma, visiting the University hospital in Kathmandu and thirty-nine healthy controls were selected, and the levels of cytokines were determined using a Luminex IS 200. We compared the levels of the cytokines in thirty-four age and gender matched pairs of case and control among three groups: healthy volunteers, cases diagnosed as PTSD, and cases without PTSD. Among the 34 pair-matched cases and controls, IL-6 was significantly higher in both PTSD positive cases [2.43 (0.00-14.54) pg/ml; p = 0.004] and PTSD negative cases [3.00 (0.92-3.86) pg/ml; p = 0.005], than in controls [0.39 (0.00-11.38) pg/ml]. IL-1β was significantly higher in PTSD positive cases [0.17 (0.00-5.27) pg/ml; p = 0.011] than in controls 0.00 (0.00-0.12) pg/ml. Other cytokines did not show significant differences. IL-6 was higher in both the trauma affected groups and IL-1β was higher in the trauma affected group with PTSD when compared to healthy controls. This supports the immune system activation hypothesis after trauma.
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Affiliation(s)
- Rishav Koirala
- Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Brain and Neuroscience Center, Nepal
- * E-mail:
| | | | - Erik Ganesh Iyer Søegaard
- Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - Hari Prasad Dhakal
- Department of Pathology and Laboratory Medicine, Nepal Cancer Hospital and Research Center, Nepal
| | | | - Edvard Hauff
- Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Suraj Bahadur Thapa
- Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Department of Psychiatry and Mental Health, IOM, TUTH, Nepal
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11
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Associations between HPA axis reactivity and PTSD and depressive symptoms: Importance of maltreatment type and puberty. Dev Psychopathol 2023; 35:130-141. [PMID: 34092276 PMCID: PMC8648873 DOI: 10.1017/s095457942100050x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The functioning of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the etiology and maintenance of depressive and posttraumatic stress disorder (PTSD) symptoms. However, different maltreatment experiences as well as the increased sensitivity of the HPA axis during puberty may alter associations between the HPA axis and mental health. To address these gaps, the current study examined the potential bidirectional associations between cortisol reactivity to a stressor, PTSD symptoms, and depressive symptoms among early adolescents across two time points, 1 year apart (n = 454; Mage = 10.98 at Time 1 and Mage = 12.11 at Time 2). Multiple-group path models tested the pathways between cortiol reactivity and mental health prior to and during puberty, for different types of maltreatment . Overall, the results showed that associations between cortisol output and symptoms of PTSD and depression were driven by those in the midst of puberty. Specifically, higher cortisol output at Time 1 was linked with higher levels of subsequent PTSD and depressive symptoms for neglected youth who had reached puberty. However, depressive symptoms predicted subsequent lower cortisol output for the physical abuse and emotional abuse groups. These findings demonstrate longitudinal links between cortisol, depressive symptoms, and PTSD symptoms among youth with different types of maltreatment histories and highlight the need to consider the reorganization of the stress system during puberty in order to advance our understanding of the HPA axis and mental health.
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12
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Berk BA, Ottka C, Hong Law T, Packer RMA, Wessmann A, Bathen-Nöthen A, Jokinen TS, Knebel A, Tipold A, Lohi H, Volk HA. Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil. Front Vet Sci 2022; 9:935430. [PMID: 36277072 PMCID: PMC9584307 DOI: 10.3389/fvets.2022.935430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 09/15/2022] [Indexed: 11/04/2022] Open
Abstract
Consumption of medium-chain triglycerides (MCT) has been shown to improve seizure control, reduce behavioural comorbidities and improve cognitive function in epileptic dogs. However, the exact metabolic pathways affected by dietary MCT remain poorly understood. In this study, we aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE). Metabolic alterations induced by a commercial MCT-DS in a population of 28 dogs with IE were evaluated in a 6-month multi-centre, prospective, randomised, double-blinded, controlled cross-over trial design. A metabolic energy requirement-based amount of 9% MCT or control oil was supplemented to the dogs' stable base diet for 3 months, followed by the alternative oil for another 3 months. A validated, quantitative nuclear magnetic resonance (NMR) spectroscopy platform was applied to pre- and postprandially collected serum samples to compare the metabolic profile between both DS and baseline. Furthermore, alterations in urinary neurotransmitter levels were explored. Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil. While the serum concentrations of total fatty acids appeared similar during both supplements, the relative concentrations of individual fatty acids differed. During MCT supplementation, the concentrations of polyunsaturated fatty acids and arachidonic acid were significantly higher than under the control oil. β-Hydroxybutyric acid levels were significantly higher under MCT supplementation. In total, four out of nine neurotransmitters were significantly altered: a significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption. In conclusion, these novel data highlight metabolic changes in lipid, amino-acid and ketone metabolism due to MCT supplementation. Understanding the metabolic response to MCT provides new avenues to develop better nutritional management with improved anti-seizure and neuroprotective effects for dogs with epilepsy, and other behavioural disorders.
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Affiliation(s)
- Benjamin Andreas Berk
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
- BrainCheck.Pet, Tierärztliche Praxis für Epilepsie, Mannheim, Germany
| | - Claudia Ottka
- Department of Veterinary Biosciences and Department of Medical and Clinical Genetics, Folkhälsan Research Center, University of Helsinki, Helsinki, Finland
- PetBiomics Ltd., Helsinki, Finland
| | - Tsz Hong Law
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Rowena Mary Anne Packer
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Annette Wessmann
- Pride Veterinary Centre, Neurology/Neurosurgery Service, Derby, United Kingdom
| | | | - Tarja Susanna Jokinen
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, Helsinki, Finland
| | - Anna Knebel
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
| | - Andrea Tipold
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
| | - Hannes Lohi
- Department of Veterinary Biosciences and Department of Medical and Clinical Genetics, Folkhälsan Research Center, University of Helsinki, Helsinki, Finland
- PetBiomics Ltd., Helsinki, Finland
| | - Holger Andreas Volk
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
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13
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Nugent NR, Armey M, Boker S, Brick L, Knopik V, McGeary JE, Spirito A, Mehl MR. Adolescents hospitalised for suicidality: biomarkers, social and affective predictors: a cohort study. BMJ Open 2022; 12:e056063. [PMID: 36192099 PMCID: PMC9535190 DOI: 10.1136/bmjopen-2021-056063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES The present research examines genomics and in vivo dynamics of family context and experienced affect following discharge from psychiatric hospitalisation for suicidal thoughts and behaviours (STBs). The purpose of this paper is to provide an overview of a new model, description of model-guided integration of multiple methods, documentation of feasibility of recruitment and retention and a description of baseline sample characteristics. DESIGN The research involved a longitudinal, multimethod observational investigation. SETTING Participants were recruited from an inpatient child and adolescent psychiatric hospital. 194 participants ages 13-18 were recruited following hospitalisation for STB. PRIMARY AND SECONDARY OUTCOME MEASURES Participants underwent a battery of clinical interviews, self-report assessments and venipuncture. On discharge, participants were provided with a phone with (1) the electronically activated recorder (EAR), permitting acoustic capture later coded for social context, and (2) ecological momentary assessment, permitting assessment of in vivo experienced affect and STB. Participants agreed to follow-ups at 3 weeks and 6 months. RESULTS A total of 71.1% of approached patients consented to participation. Participants reported diversity in gender identity (11.6% reported transgender or other gender identity) and sexual orientation (47.6% reported heterosexual or straight sexual orientation). Clinical interviews supported a range of diagnoses with the largest proportion of participants meeting criteria for major depressive disorder (76.9%). History of trauma/maltreatment was prevalent. Enrolment rates and participant characteristics were similar to other observational studies. CONCLUSIONS The research protocol characterises in vivo, real-world experienced affect and observed family context as associated with STB in adolescents during the high-risk weeks post discharge, merging multiple fields of study.
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Affiliation(s)
- Nicole R Nugent
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
| | - Michael Armey
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
- Department of Psychosocial Research, Butler Hospital, Providence, Rhode Island, USA
| | - Steven Boker
- Department of Psychology, University of Virginia, Charlottesville, Virginia, USA
| | - Leslie Brick
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
| | - Valerie Knopik
- Department of Human Development and Family Studies, Purdue University, West Lafayette, Indiana, USA
| | - John E McGeary
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
- Providence VA Medical Center, Providence, Rhode Island, USA
| | - Anthony Spirito
- Department of Psychiatry and Human Behavior, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
| | - Matthias R Mehl
- Department of Psychology, Arizona State University, Tempe, Arizona, USA
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14
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Schmidt T, Meller S, Talbot SR, Berk BA, Law TH, Hobbs SL, Meyerhoff N, Packer RMA, Volk HA. Urinary Neurotransmitter Patterns Are Altered in Canine Epilepsy. Front Vet Sci 2022; 9:893013. [PMID: 35651965 PMCID: PMC9150448 DOI: 10.3389/fvets.2022.893013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 04/22/2022] [Indexed: 12/12/2022] Open
Abstract
Epilepsy is the most common chronic neurological disease in humans and dogs. Epilepsy is thought to be caused by an imbalance of excitatory and inhibitory neurotransmission. Intact neurotransmitters are transported from the central nervous system to the periphery, from where they are subsequently excreted through the urine. In human medicine, non-invasive urinary neurotransmitter analysis is used to manage psychological diseases, but not as yet for epilepsy. The current study aimed to investigate if urinary neurotransmitter profiles differ between dogs with epilepsy and healthy controls. A total of 223 urine samples were analysed from 63 dogs diagnosed with idiopathic epilepsy and 127 control dogs without epilepsy. The quantification of nine urinary neurotransmitters was performed utilising mass spectrometry technology. A significant difference between urinary neurotransmitter levels (glycine, serotonin, norepinephrine/epinephrine ratio, ɤ-aminobutyric acid/glutamate ratio) of dogs diagnosed with idiopathic epilepsy and the control group was found, when sex and neutering status were accounted for. Furthermore, an influence of antiseizure drug treatment upon the urinary neurotransmitter profile of serotonin and ɤ-aminobutyric acid concentration was revealed. This study demonstrated that the imbalances in the neurotransmitter system that causes epileptic seizures also leads to altered neurotransmitter elimination in the urine of affected dogs. Urinary neurotransmitters have the potential to serve as valuable biomarkers for diagnostics and treatment monitoring in canine epilepsy. However, more research on this topic needs to be undertaken to understand better the association between neurotransmitter deviations in the brain and urine neurotransmitter concentrations in dogs with idiopathic epilepsy.
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Affiliation(s)
- Teresa Schmidt
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
| | - Sebastian Meller
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
| | - Steven R. Talbot
- Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany
| | - Benjamin A. Berk
- BrainCheck.Pet – Tierärztliche Praxis für Epilepsie, Sachsenstraße, Mannheim, Germany
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Tsz H. Law
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Sarah L. Hobbs
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Nina Meyerhoff
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
| | - Rowena M. A. Packer
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
| | - Holger A. Volk
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany
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15
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Tanelian A, Nankova B, Miari M, Nahvi RJ, Sabban EL. Resilience or susceptibility to traumatic stress: Potential influence of the microbiome. Neurobiol Stress 2022; 19:100461. [PMID: 35789769 PMCID: PMC9250071 DOI: 10.1016/j.ynstr.2022.100461] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 05/13/2022] [Accepted: 05/15/2022] [Indexed: 11/24/2022] Open
Abstract
Exposure to traumatic stress is a major risk factor for development of neuropsychiatric disorders in a sub-population of individuals, while others remain resilient. The mechanisms and contributing factors differentiating between these phenotypes are still unclear. We hypothesize that inter-individual differences in the microbial composition and function contribute to host resilience or susceptibility to stress-induced psychopathologies. The current study aimed to characterize gut microbial community before and after exposure to traumatic stress in an animal model of PTSD. Sprague-Dawley male rats were randomly divided into unstressed controls and experimental group subjected to Single Prolonged Stress (SPS). After 14 days, behavioral analyses were performed using Open Field, Social Interaction and Elevated Plus Maze tests. Based on the anxiety measures, the SPS group was further subdivided into resilient (SPS-R) and susceptible (SPS–S) cohorts. The animals were sacrificed after the last behavioral test and cecum, colon, hippocampus, and medial prefrontal cortex were dissected. Prior to SPS and immediately after Open Field test, fecal samples were collected from each rat for 16S V3–V4 ribosomal DNA sequencing, whereas urine samples were collected before SPS, 90 min into immobilization and on the day of sacrifice to measure epinephrine and norepinephrine levels. Analyses of the fecal microbiota revealed significant differences in microbial communities and in their predictive functionality among the groups before and after SPS stressors. Before SPS, the SPS-S subgroup harbored microbiota with an overall pro-inflammatory phenotype, whereas SPS-R subgroup had microbiota with an overall anti-inflammatory phenotype, with predictive functional pathways enriched in carbohydrate and lipid metabolism and decreased in amino acid metabolism and neurodegenerative diseases. After SPS, the gut microbial communities and their predictive functionality shifted especially in SPS cohorts, with volatility at the genus level correlating inversely with Anxiety Index. In line with the alterations seen in the gut microbiota, the levels of cecal short chain fatty acids were also altered, with SPS-S subgroup having significantly lower levels of acetate, valerate and caproate. The levels of acetate inversely correlated with Anxiety Index. Interestingly, urinary epinephrine and norepinephrine levels were also higher in the SPS-S subgroup at baseline and during stress, indicative of an altered sympathoadrenal stress axis. Finally, shorter colon (marker of intestinal inflammation) and a lower claudin-5 protein expression (marker for increased blood brain barrier permeability) were observed in the SPS-S subgroup. Taken together, our results suggest microbiota is a potential factor in predisposing subjects either to stress susceptibility or resilience. Moreover, SPS triggered significant shifts in the gut microbiota, their metabolites and brain permeability. These findings could lead to new therapeutic directions for PTSD possibly through the controlled manipulation of gut microbiota. It may enable early identification of individuals more likely to develop prolonged anxiogenic symptoms following traumatic stress.
Preexisting individual differences in microbiome relate to host's stress response. Shift in the microbial composition differs in SPS-R and SPS-S subgroups after SPS. Cecal levels of acetate in SPS subgroups correlate inversely with anxiety index. Basal and stress-induced urinary catecholamine levels are higher in SPS-S subgroup. SPS-S subgroup has shorter colon, less cecal SCFA and lower brain TJ protein.
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16
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Raut SB, Marathe PA, van Eijk L, Eri R, Ravindran M, Benedek DM, Ursano RJ, Canales JJ, Johnson LR. Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. Pharmacol Ther 2022; 239:108195. [PMID: 35489438 DOI: 10.1016/j.pharmthera.2022.108195] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/19/2022] [Accepted: 04/20/2022] [Indexed: 12/20/2022]
Abstract
Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.
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Affiliation(s)
- Sanket B Raut
- Schools of Psychological Sciences, College of Health and Medicine, University of Tasmania, TAS 7250, Australia
| | - Padmaja A Marathe
- Department of Pharmacology and Therapeutics, Seth GS Medical College & KEM Hospital, Parel, Mumbai 400 012, India
| | - Liza van Eijk
- Department of Psychology, College of Healthcare Sciences, James Cook University, QLD 4811, Australia
| | - Rajaraman Eri
- Health Sciences, College of Health and Medicine, University of Tasmania, TAS 7250, Australia
| | - Manoj Ravindran
- Medicine, College of Health and Medicine, University of Tasmania, TAS 7250, Australia; Department of Psychiatry, North-West Private Hospital, Burnie TAS 7320, Australia
| | - David M Benedek
- Centre for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University School of Medicine, Bethesda, MD 20814, USA
| | - Robert J Ursano
- Centre for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University School of Medicine, Bethesda, MD 20814, USA
| | - Juan J Canales
- Schools of Psychological Sciences, College of Health and Medicine, University of Tasmania, TAS 7250, Australia
| | - Luke R Johnson
- Schools of Psychological Sciences, College of Health and Medicine, University of Tasmania, TAS 7250, Australia; Centre for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University School of Medicine, Bethesda, MD 20814, USA.
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17
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Radford KD, Berman RY, Jaiswal S, Kim SY, Zhang M, Spencer HF, Choi KH. Enhanced Fear Memories and Altered Brain Glucose Metabolism ( 18F-FDG-PET) following Subanesthetic Intravenous Ketamine Infusion in Female Sprague-Dawley Rats. Int J Mol Sci 2022; 23:ijms23031922. [PMID: 35163844 PMCID: PMC8836808 DOI: 10.3390/ijms23031922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/30/2022] [Accepted: 02/04/2022] [Indexed: 11/30/2022] Open
Abstract
Although women and men are equally likely to receive ketamine following traumatic injury, little is known regarding sex-related differences in the impact of ketamine on traumatic memory. We previously reported that subanesthetic doses of an intravenous (IV) ketamine infusion following fear conditioning impaired fear extinction and altered regional brain glucose metabolism (BGluM) in male rats. Here, we investigated the effects of IV ketamine infusion on fear memory, stress hormone levels, and BGluM in female rats. Adult female Sprague–Dawley rats received a single IV ketamine infusion (0, 2, 10, or 20 mg/kg, over a 2-h period) following auditory fear conditioning (three pairings of tone and footshock). Levels of plasma stress hormones, corticosterone (CORT) and progesterone, were measured after the ketamine infusion. Two days after ketamine infusion, fear memory retrieval, extinction, and renewal were tested over a three-day period. The effects of IV ketamine infusion on BGluM were determined using 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG-PET) and computed tomography (CT). The 2 and 10 mg/kg ketamine infusions reduced locomotor activity, while 20 mg/kg infusion produced reduction (first hour) followed by stimulation (second hour) of activity. The 10 and 20 mg/kg ketamine infusions significantly elevated plasma CORT and progesterone levels. All three doses enhanced fear memory retrieval, impaired fear extinction, and enhanced cued fear renewal in female rats. Ketamine infusion produced dose-dependent effects on BGluM in fear- and stress-sensitive brain regions of female rats. The current findings indicate that subanesthetic doses of IV ketamine produce robust effects on the hypothalamic–pituitary–adrenal (HPA) axis and brain energy utilization that may contribute to enhanced fear memory observed in female rats.
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Affiliation(s)
- Kennett D. Radford
- Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD 20814, USA;
| | - Rina Y. Berman
- Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA; (R.Y.B.); (M.Z.)
| | - Shalini Jaiswal
- Biomedical Research Imaging Core (BRIC), Department of Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD 20814, USA;
| | - Sharon Y. Kim
- Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA; (S.Y.K.); (H.F.S.)
| | - Michael Zhang
- Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA; (R.Y.B.); (M.Z.)
| | - Haley F. Spencer
- Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA; (S.Y.K.); (H.F.S.)
| | - Kwang H. Choi
- Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD 20814, USA;
- Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA; (R.Y.B.); (M.Z.)
- Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA; (S.Y.K.); (H.F.S.)
- Department of Psychiatry, F. E. Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA
- Correspondence: ; Tel.: +1-301-295-2682
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18
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Jayan D, deRoon-Cassini TA, Sauber G, Hillard CJ, Fitzgerald JM. A cluster analytic approach to examining the role of cortisol in the development of post-traumatic stress and dysphoria in adult traumatic injury survivors. Psychoneuroendocrinology 2022; 135:105450. [PMID: 34775251 PMCID: PMC8686692 DOI: 10.1016/j.psyneuen.2021.105450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 10/10/2021] [Accepted: 10/11/2021] [Indexed: 01/03/2023]
Abstract
Identification of specific risk factors for posttraumatic stress disorder (PTSD) versus depression after trauma has been challenging, in part due to the high comorbidity of these disorders. As exposure to trauma triggers activation of the hypothalamic-pituitary-adrenal (HPA)-axis, examining atypical stress responses via HPA-axis hormones, namely cortisol, may help in the delineation of these disorders. Indeed, extant research demonstrates that, following stress, individuals with chronic PTSD exhibit hypocortisolism (e.g., lower cortisol response than controls), while those with chronic depression exhibit hypercortisolism (e.g., higher response than controls). Less is known about the role of cortisol and these seemingly disparate profiles immediately following traumatic injury as well as whether cortisol can be used as a predictor of future development of PTSD versus depression symptoms. In this study cortisol was measured blood from 172 traumatic injury survivors during hospitalization (on average 2.5 days post-injury). PTSD and depression severity were assessed from Clinician Assessed PTSD Scale (CAPS-5) six-eight months later using a two-factor dimensional approach that measures trauma-specific symptoms of PTSD versus dysphoria (akin to depression). Cluster analysis was used to group individuals based on post-injury cortisol, PTSD, and dysphoria. Results demonstrated that trauma survivors who only developed symptoms of dysphoria at six months (with minimal symptoms of PTSD) were differentiated by high post-injury cortisol compared to other groups. By contrast, individuals who developed symptoms of both PTSD and dysphoria were differentiated by low post-injury cortisol and most severe symptoms of PTSD. Findings provide support for the presence of subgroups of trauma survivors defined, in part, by post-trauma cortisol.
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Affiliation(s)
- Devi Jayan
- Department of Psychology, Marquette University, 317 Cramer Hall, Milwaukee 53233, USA
| | - Terri A deRoon-Cassini
- Departments of Trauma & Acute Care Surgery, Psychiatry & Behavioral Medicine, and the Institute for Health & Equity, Comprehensive Injury Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
| | - Garrett Sauber
- Department of Pharmacology and Toxicology and Neuroscience Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
| | - Cecilia J Hillard
- Department of Pharmacology and Toxicology and Neuroscience Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
| | - Jacklynn M Fitzgerald
- Department of Psychology, Marquette University, 317 Cramer Hall, Milwaukee 53233, USA.
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19
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The Molecular Biology of Susceptibility to Post-Traumatic Stress Disorder: Highlights of Epigenetics and Epigenomics. Int J Mol Sci 2021; 22:ijms221910743. [PMID: 34639084 PMCID: PMC8509551 DOI: 10.3390/ijms221910743] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/28/2021] [Accepted: 09/29/2021] [Indexed: 12/13/2022] Open
Abstract
Exposure to trauma is one of the most important and prevalent risk factors for mental and physical ill-health. Excessive or prolonged stress exposure increases the risk of a wide variety of mental and physical symptoms. However, people differ strikingly in their susceptibility to develop signs and symptoms of mental illness after traumatic stress. Post-traumatic stress disorder (PTSD) is a debilitating disorder affecting approximately 8% of the world’s population during their lifetime, and typically develops after exposure to a traumatic event. Despite that exposure to potentially traumatizing events occurs in a large proportion of the general population, about 80–90% of trauma-exposed individuals do not develop PTSD, suggesting an inter-individual difference in vulnerability to PTSD. While the biological mechanisms underlying this differential susceptibility are unknown, epigenetic changes have been proposed to underlie the relationship between exposure to traumatic stress and the susceptibility to develop PTSD. Epigenetic mechanisms refer to environmentally sensitive modifications to DNA and RNA molecules that regulate gene transcription without altering the genetic sequence itself. In this review, we provide an overview of various molecular biological, biochemical and physiological alterations in PTSD, focusing on changes at the genomic and epigenomic level. Finally, we will discuss how current knowledge may aid us in early detection and improved management of PTSD patients.
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Gazarini L, Stern CA, Takahashi RN, Bertoglio LJ. Interactions of Noradrenergic, Glucocorticoid and Endocannabinoid Systems Intensify and Generalize Fear Memory Traces. Neuroscience 2021; 497:118-133. [PMID: 34560200 DOI: 10.1016/j.neuroscience.2021.09.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 12/13/2022]
Abstract
Systemic administration of drugs that activate the noradrenergic or glucocorticoid system potentiates aversive memory consolidation and reconsolidation. The opposite happens with the stimulation of endocannabinoid signaling under certain conditions. An unbalance of these interacting neurotransmitters can lead to the formation and maintenance of traumatic memories, whose strength and specificity attributes are often maladaptive. Here we aimed to investigate whether originally low-intensity and precise contextual fear memories would turn similar to traumatic ones in rats systemically administered with adrenaline, corticosterone, and/or the cannabinoid type-1 receptor antagonist/inverse agonist AM251 during consolidation or reconsolidation. The high dose of each pharmacological agent evaluated significantly increased freezing times at test in the conditioning context one and nine days later when given alone post-acquisition or post-retrieval. Their respective low dose produced no relative changes when given separately, but co-treatment of adrenaline with corticosterone or AM251 and the three drugs combined, but not corticosterone with AM251, produced results equivalent to those mentioned initially. Neither the high nor the low dose of adrenaline, corticosterone, or AM251 altered freezing times at test in a novel, neutral context two and ten days later. In contrast, animals receiving the association of their low dose exhibited significantly higher freezing times than controls. Together, the results indicate that newly acquired and destabilized threat memory traces become more intense and generalized after a combined interference acting synergistically and mimicking that reported in patients presenting stress-related psychiatric conditions.
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Affiliation(s)
- Lucas Gazarini
- Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Universidade Federal de Mato Grosso do Sul, Três Lagoas, MS, Brazil.
| | - Cristina A Stern
- Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - Reinaldo N Takahashi
- Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
| | - Leandro J Bertoglio
- Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
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21
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Clouston SAP, Muñiz Terrera G, Rodgers JL, O'Keefe P, Mann F, Lewis NA, Wänström L, Kaye J, Hofer SM. Cohort and Period Effects as Explanations for Declining Dementia Trends and Cognitive Aging. POPULATION AND DEVELOPMENT REVIEW 2021; 47:611-637. [PMID: 36937313 PMCID: PMC10021404 DOI: 10.1111/padr.12409] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Studies have reported that the age-adjusted incidence of cognitive impairment and dementia may have decreased over the past two decades. Aging is the predominant risk factor for Alzheimer's disease and related dementias and for neurocognitive decline. However, aging cannot explain changes in overall age-adjusted incidence of dementia. The objective of this position paper was to describe the potential for cohort and period effects in cognitive decline and incidence of dementia. Cohort effects have long been reported in demographic literature, but starting in the early 1980s, researchers began reporting cohort trends in cognitive function. At the same time, period effects have emerged in economic factors and stressors in early and midlife that may result in reduced cognitive dysfunction. Recognizing that aging individuals today were once children and adolescents, and that research has clearly noted that childhood cognitive performance is a primary determinant of old-age cognitive performance, this is the first study that proposes the need to connect known cohort effects in childhood cognition with differences in late-life functioning.
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Affiliation(s)
- Sean A P Clouston
- Program in Public Health and Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
| | - Graciela Muñiz Terrera
- Biostatistics and Epidemiology, Center for Dementia Prevention, University of Edinburgh, Edinburgh, UK
| | - Joseph Lee Rodgers
- Department of Psychology and Human Development, Vanderbilt University, Nashville, TN, USA
| | | | - Frank Mann
- Program in Public Health and Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
| | - Nathan A Lewis
- Department of Psychology, University of Victoria, Victoria, BC
| | - Linda Wänström
- Department of Computer and Informational Science, Linköping University, Linköping, Sweden
| | - Jeffrey Kaye
- Oregon Center for Aging and Technology, Oregon Health and Sciences University, and NIA-Layton Aging & Alzheimer's Disease Center, Portland, OR, USA
| | - Scott M Hofer
- Department of Psychology, University of Victoria, Victoria, BC
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22
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Ploski JE, Vaidya VA. The Neurocircuitry of Posttraumatic Stress Disorder and Major Depression: Insights Into Overlapping and Distinct Circuit Dysfunction-A Tribute to Ron Duman. Biol Psychiatry 2021; 90:109-117. [PMID: 34052037 PMCID: PMC8383211 DOI: 10.1016/j.biopsych.2021.04.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 04/13/2021] [Accepted: 04/13/2021] [Indexed: 12/14/2022]
Abstract
The neurocircuitry that contributes to the pathophysiology of posttraumatic stress disorder and major depressive disorder, psychiatric conditions that exhibit a high degree of comorbidity, likely involves both overlapping and unique structural and functional changes within multiple limbic brain regions. In this review, we discuss neurobiological alterations that are associated with posttraumatic stress disorder and major depressive disorder and highlight both similarities and differences that may exist between these disorders to argue for the existence of a shared neurobiology. We highlight the key contributions based on preclinical studies, emerging from the late Professor Ronald Duman's research, that have shaped our understanding of the neurocircuitry that contributes to both the etiopathology and treatment of major depressive disorder and posttraumatic stress disorder.
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Affiliation(s)
- Jonathan E. Ploski
- Department of Neuroscience and Molecular & Cell Biology, School of Behavioral and Brain Sciences, University of Texas at Dallas, GR41, 800 W Campbell Road, Richardson, TX 75080-3021, USA
| | - Vidita A. Vaidya
- Department of Biological Sciences, Tata Institute of Fundamental Research, 1 Homi Bhabha Road, Colaba, Mumbai, Maharashtra, 400005, India
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23
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Rittenberger M, Ostrowski-Delahanty S, Woods K. The impact of trauma exposure on headache outcomes. CHILDRENS HEALTH CARE 2021. [DOI: 10.1080/02739615.2021.1913163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Morgan Rittenberger
- NeuroDevelopmental Science Center, Akron Children’s Hospital, Akron, Ohio, USA
- Speech and Hearing, Cleveland State University, Cleveland, Ohio, USA
| | | | - Kristine Woods
- NeuroDevelopmental Science Center, Akron Children’s Hospital, Akron, Ohio, USA
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24
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Warren WG, Papagianni EP, Stevenson CW, Stubbendorff C. In it together? The case for endocannabinoid-noradrenergic interactions in fear extinction. Eur J Neurosci 2021; 55:952-970. [PMID: 33759226 DOI: 10.1111/ejn.15200] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 01/26/2021] [Accepted: 03/17/2021] [Indexed: 12/18/2022]
Abstract
Anxiety and trauma-related disorders, such as post-traumatic stress disorder (PTSD), are debilitating mental illnesses with great personal and socioeconomic costs. Examining memory formation and relevant behavioural responding associated with aversive stimuli may improve our understanding of the neurobiology underlying fear memory processing and PTSD treatment. The neurocircuitry underpinning learned fear and its inhibition through extinction is complex, involving synergistic interactions between different neurotransmitter systems in inter-connected brain areas. Endocannabinoid and noradrenergic transmission have both been implicated separately in fear memory processing and PTSD, but potential interactions between these systems in relation to fear extinction have received little attention to date. Their receptors are expressed together in brain areas crucial for fear extinction, which is enhanced by both cannabinoid and noradrenergic receptor activation in these areas. Moreover, cannabinoid signalling modulates the activity of locus coeruleus noradrenaline (NA) neurons and the release of NA in the medial prefrontal cortex, a brain area that is crucial for fear extinction. Interestingly, endocannabinoid-noradrenergic system interactions have been shown to regulate the encoding and retrieval of fear memory. Thus, noradrenergic regulation of fear extinction may also be driven indirectly in part via cannabinoid receptor signalling. In this perspective paper, we collate the available relevant literature and propose a synergistic role for the endocannabinoid and noradrenergic systems in regulating fear extinction, the study of which may further our understanding of the neurobiological substrates of PTSD and its treatment.
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Affiliation(s)
- William G Warren
- School of Biosciences, University of Nottingham, Loughborough, UK
| | | | - Carl W Stevenson
- School of Biosciences, University of Nottingham, Loughborough, UK
| | - Christine Stubbendorff
- School of Biosciences, University of Nottingham, Loughborough, UK.,Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy
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25
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Sadeh Y, Dekel R, Brezner A, Landa J, Silberg T. Child and Family Factors Associated With Posttraumatic Stress Responses Following a Traumatic Medical Event: The Role of Medical Team Support. J Pediatr Psychol 2021; 45:1063-1073. [PMID: 32968802 DOI: 10.1093/jpepsy/jsaa070] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 06/13/2020] [Accepted: 07/23/2020] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES This study examined the contribution of pretrauma psychosocial factors (child emotional functioning, family resources, family functioning, and social support) and environmental factors (mother's posttraumatic stress symptoms [PTSSs], medical team support [MTS]) to PTSSs of injured or seriously ill children within a pediatric rehabilitation setting. It was hypothesized that psychosocial variables would be strongly associated with child's PTSS; that mother's PTSS and MTS would mediate the association between psychosocial factors and child's PTSS; that mother's report on child's PTSS would mediate the association between mother's PTSS and child's PTSS. METHODS Participants were 196 children hospitalized following an injury/illness and assessed M = 47.7 days postevent. Children completed measures of PTSS, mothers completed measures of their own PTSS, child's PTSS, and pretrauma psychosocial factors. Family's therapist completed a MTS measure. Structural equation modeling was employed to evaluate the study hypotheses. RESULTS Pretrauma family structure and resources were associated with child's self-reported PTSS; each pretrauma variable and mother's report of child's PTSS was significantly associated. Although mother's PTSS was not directly associated with child's PTSS, this relationship was mediated by mother's report of child's PTSS. MTS mediated the relationship between pretrauma social support and mother's PTSS. CONCLUSION This study further explicates the utility of a biopsychosocial framework in predicting childhood PTSS. Findings confirm the role of pretrauma factors and environmental factors at the peritrauma period in the development of PTSS following a pediatric injury/illness. Mother's PTSS and MTS may be appropriate targets for prevention and early intervention.
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Affiliation(s)
- Yaara Sadeh
- The Louis and Gabi Weisfeld School of Social Work, Bar-Ilan University.,Department of Pediatric Rehabilitation, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center
| | - Rachel Dekel
- The Louis and Gabi Weisfeld School of Social Work, Bar-Ilan University
| | - Amichai Brezner
- Department of Pediatric Rehabilitation, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center
| | - Jana Landa
- Department of Pediatric Rehabilitation, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center.,Sackler Faculty of Medicine, Tel-Aviv University
| | - Tamar Silberg
- Department of Pediatric Rehabilitation, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center.,Holland Bloorview Kids Rehabilitation Hospital.,Department of Psychology, Bar-Ilan University
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26
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Early Life Stress and Pediatric Posttraumatic Stress Disorder. Brain Sci 2020; 10:brainsci10030169. [PMID: 32183256 PMCID: PMC7139542 DOI: 10.3390/brainsci10030169] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 03/07/2020] [Accepted: 03/12/2020] [Indexed: 11/16/2022] Open
Abstract
Traumatic stress exposure during critical periods of development may have essential and long-lasting effects on the physical and mental health of individuals. Two thirds of youth are exposed to potentially traumatic experiences by the age of 17, and approximately 5% of adolescents meet lifetime criteria for posttraumatic stress disorder (PTSD). The role of the stress system is the maintenance of homeostasis in the presence of real/perceived and acute/chronic stressors. Early-life stress (ELS) has an impact on neuronal brain networks involved in stress reactions, and could exert a programming effect on glucocorticoid signaling. Studies on pediatric PTSD reveal diverse neuroendocrine responses to adverse events and related long-term neuroendocrine and epigenetic alterations. Neuroendocrine, neuroimaging, and genetic studies in children with PTSD and ELS experiences are crucial in understanding risk and resilience factors, and also the natural history of PTSD.
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27
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Mac Gillavry DW, Ullrich D. A novel theory on the predictive value of variation in the β-endorphin system on the risk and severity of PTSD. MILITARY PSYCHOLOGY 2020; 32:247-260. [PMID: 38536347 PMCID: PMC10013490 DOI: 10.1080/08995605.2020.1730111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 09/18/2019] [Indexed: 02/08/2023]
Abstract
Despite growing interest in genetic and psychosocial indicators of heightened susceptibility to posttraumatic stress disorder (PTSD), a predictive model, which explains why some individuals develop PTSD in response to life-threatening traumatic events, while others, when faced with the same or similar experiences, do not, has thus far remained out of reach. In this paper, we review the literature on gene-environment interactions in β-endorphin system functioning with regard to PTSD and suggest that variation, both genetic and with regard to environmental stimuli, in systems which, like the β-endorphin system, distort human perception of life-threatening traumatic experiences may account for some of the variance in resilience to the disorder. Given the role of β-endorphin in both social connections and physical exercise, this becomes especially relevant with regard to military selection, training, and leadership processes.
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Affiliation(s)
| | - David Ullrich
- Department of Military Leadership, University of Defence, Brno, Czech Republic
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28
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Tatarinova TV, Deiss T, Franckle L, Beaven S, Davis J. The Impact of MNRI Therapy on the Levels of Neurotransmitters Associated with Inflammatory Processes. Int J Mol Sci 2020; 21:E1358. [PMID: 32085403 PMCID: PMC7072967 DOI: 10.3390/ijms21041358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 02/13/2020] [Accepted: 02/14/2020] [Indexed: 01/02/2023] Open
Abstract
The neurotransmitter levels of representatives from five different diagnosis groups were tested before and after participation in the MNRI®-Masgutova Neurosensorimotor Reflex Intervention. The purpose of this study was to ascertain neurological impact on (1) Developmental disorders, (2) Anxiety disorders/OCD (Obsessive Compulsive Disorder), PTSD (Post-Traumatic Stress disorder), (3) Palsy/Seizure disorders, (4) ADD/ADHD (Attention Deficit Disorder/Attention Deficit Disorder Hyperactive Disorder), and (5) ASD (Autism Spectrum Disorder) disorders. Each participant had a form of neurological dysregulation and typical symptoms respective to their diagnosis. These diagnoses have a severe negative impact on the quality of life, immunity, stress coping, cognitive skills, and social assimilation. This study showed a trend towards optimization and normalization of neurological and immunological functioning, thus supporting the claim that the MNRI method is an effective non-pharmacological neuromodulation treatment of neurological disorders. The effects of MNRI on inflammation have not yet been assessed. The resulting post-MNRI changes in participants' neurotransmitters show significant adjustments in the regulation of the neurotransmitter resulting in being calmer, a decrease of hypervigilance, an increase in stress resilience, behavioral and emotional regulation improvements, a more positive emotional state, and greater control of cognitive processes. In this paper, we demonstrate that the MNRI approach is an intervention that reduces inflammation. It is also likely to reduce oxidative stress and encourage homeostasis of excitatory neurotransmitters. MNRI may facilitate neurodevelopment, build stress resiliency, neuroplasticity, and optimal learning opportunity. There have been no reported side effects of MNRI treatments.
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Affiliation(s)
- Tatiana V. Tatarinova
- Department of Biology, University of La Verne, La Verne, CA 91750, USA
- Functional Genomics Group, Vavilov Institute for General Genetics, Moscow 119991, Russia
- Forest Genomics Laboratory, Siberian Federal University, Krasnoyarsk 660041, Russia
- Bioinformatics Center, Information Transmission Problems Institute, Moscow 127051, Russia
| | - Trina Deiss
- Research Department, United1Front Foundation, Minneapolis, MN 55111, USA;
| | - Lorri Franckle
- Laser Health Department, Laser Health, Orlando, FL 33709, USA;
| | - Susan Beaven
- Family Medicine, St. Petersburg Free Clinic, St. Petersburg, FL 33701, USA;
| | - Jeffrey Davis
- Family Medicine, Prairie Health and Wellness, Wichita, KS 67206, USA;
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MEDICAL, PSYCHOLOGICAL AND LEGAL ASPECTS TO SUBSTANTIATE THE CONCEPT OF REHABILITATION FOR MILITARY PERSONNEL – PARTICIPANTS OF THE ANTI-TERRORIST OPERATION. WORLD OF MEDICINE AND BIOLOGY 2020. [DOI: 10.26724/2079-8334-2020-1-71-154-158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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30
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Bryant RA. Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World Psychiatry 2019; 18:259-269. [PMID: 31496089 PMCID: PMC6732680 DOI: 10.1002/wps.20656] [Citation(s) in RCA: 226] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Post-traumatic stress disorder (PTSD) is arguably the most common psychiatric disorder to arise after exposure to a traumatic event. Since its formal introduction in the DSM-III in 1980, knowledge has grown significantly regarding its causes, maintaining mechanisms and treatments. Despite this increased understanding, however, the actual definition of the disorder remains controversial. The DSM-5 and ICD-11 define the disorder differently, reflecting disagreements in the field about whether the construct of PTSD should encompass a broad array of psychological manifestations that arise after trauma or should be focused more specifically on trauma memory phenomena. This controversy over clarifying the phenotype of PTSD has limited the capacity to identify biomarkers and specific mechanisms of traumatic stress. This review provides an up-to-date outline of the current definitions of PTSD, its known prevalence and risk factors, the main models to explain the disorder, and evidence-supported treatments. A major conclusion is that, although trauma-focused cognitive behavior therapy is the best-validated treatment for PTSD, it has stagnated over recent decades, and only two-thirds of PTSD patients respond adequately to this intervention. Moreover, most people with PTSD do not access evidence-based treatment, and this situation is much worse in low- and middle-income countries. Identifying processes that can overcome these major barriers to better management of people with PTSD remains an outstanding challenge.
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31
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Kosman KA, Levy-Carrick NC. Positioning Psychiatry as a Leader in Trauma-Informed Care (TIC): the Need for Psychiatry Resident Education. ACADEMIC PSYCHIATRY : THE JOURNAL OF THE AMERICAN ASSOCIATION OF DIRECTORS OF PSYCHIATRIC RESIDENCY TRAINING AND THE ASSOCIATION FOR ACADEMIC PSYCHIATRY 2019; 43:429-434. [PMID: 30693465 DOI: 10.1007/s40596-019-01020-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 01/03/2019] [Indexed: 06/09/2023]
Affiliation(s)
- Katherine A Kosman
- Brigham and Women's Hospital, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
| | - Nomi C Levy-Carrick
- Brigham and Women's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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32
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Bhattacharya S, Fontaine A, MacCallum PE, Drover J, Blundell J. Stress Across Generations: DNA Methylation as a Potential Mechanism Underlying Intergenerational Effects of Stress in Both Post-traumatic Stress Disorder and Pre-clinical Predator Stress Rodent Models. Front Behav Neurosci 2019; 13:113. [PMID: 31191267 PMCID: PMC6547031 DOI: 10.3389/fnbeh.2019.00113] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 05/07/2019] [Indexed: 12/12/2022] Open
Abstract
Although most humans will experience some type of traumatic event in their lifetime only a small set of individuals will go on to develop post-traumatic stress disorder (PTSD). Differences in sex, age, trauma type, and comorbidity, along with many other elements, contribute to the heterogenous manifestation of this disorder. Nonetheless, aberrant hypothalamus-pituitary-adrenal (HPA) axis activity, especially in terms of cortisol and glucocorticoid receptor (GR) alterations, has been postulated as a tenable factor in the etiology and pathophysiology of PTSD. Moreover, emerging data suggests that the harmful effects of traumatic stress to the HPA axis in PTSD can also propagate into future generations, making offspring more prone to psychopathologies. Predator stress models provide an ethical and ethologically relevant way to investigate tentative mechanisms that are thought to underlie this phenomenon. In this review article, we discuss findings from human and laboratory predator stress studies that suggest changes to DNA methylation germane to GRs may underlie the generational effects of trauma transmission. Understanding mechanisms that promote stress-induced psychopathology will represent a major advance in the field and may lead to novel treatments for such devastating, and often treatment-resistant trauma and stress-disorders.
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Affiliation(s)
- Sriya Bhattacharya
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Audrey Fontaine
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada.,Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie, Sorbonne Universités, Paris, France
| | - Phillip E MacCallum
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
| | - James Drover
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Jacqueline Blundell
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
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33
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Kim YK, Amidfar M, Won E. A review on inflammatory cytokine-induced alterations of the brain as potential neural biomarkers in post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 2019; 91:103-112. [PMID: 29932946 DOI: 10.1016/j.pnpbp.2018.06.008] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 06/17/2018] [Accepted: 06/18/2018] [Indexed: 12/25/2022]
Abstract
The heterogeneity of post-traumatic stress disorder (PTSD) symptoms indicates that multiple neurobiological mechanisms underlie the pathophysiology of the condition. However, no generally accepted PTSD biomarkers in clinical practice currently exist. The sequential responses to recurrent and chronic stress by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) system are considered to play a significant role in the onset and progression of PTSD. Decreased activity of the HPA axis and parasympathetic nervous system, along with increased activity of the sympathetic nervous system, have been observed in PTSD, which may lead to increased levels of proinflammatory cytokines. Such heightened activity of the immune system may cause alterations in the structure and function of brain regions-for example, the amygdala, hippocampus, medial prefrontal cortex, anterior cingulate cortex, and insula-through changes in levels of serotonin and kynurenine pathway metabolites, and direct neurotoxic effects of cytokines. Although chronic inflammation-induced alterations in brain regions critical in controlling emotional behavior and fear regulation may represent a strong candidate biomarker of PTSD, future studies are necessary to further elucidate inflammation-associated neural biomarkers of PTSD. Continued research on therapeutic methods that involve the normalization of the HPA axis, ANS, and immune system is expected to contribute to the development of novel ways to treat PTSD.
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Affiliation(s)
- Yong-Ku Kim
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Meysam Amidfar
- Department of Neuroscience, Fasa University of Medical Sciences, Fasa, Iran
| | - Eunsoo Won
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea.
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34
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Li Y, Hassett AL, Seng JS. Exploring the mutual regulation between oxytocin and cortisol as a marker of resilience. Arch Psychiatr Nurs 2019; 33:164-173. [PMID: 30927986 PMCID: PMC6442937 DOI: 10.1016/j.apnu.2018.11.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Revised: 11/12/2018] [Accepted: 11/17/2018] [Indexed: 12/11/2022]
Abstract
Early trauma can increase the risk for developing posttraumatic stress disorder (PTSD) in adulthood. Early trauma has also been associated with the dysregulation between the hypothalamic-pituitary-adrenal (HPA) and oxytocin systems and may influence the co-regulation between these two systems. But whether the mutual regulation of the two systems represents a sign of resilience and/or mutual dysregulation could be a sign of vulnerability to PTSD and the dissociative subtype of PTSD (PTSD-D) is unknown. The study aims to synthesize and conduct a preliminary test of a conceptual model of the mutual regulation between these two systems as a marker of resilience. We analyzed a pilot data with 22 pregnant women in 3 groups (PTSD only, PTSD-D, and trauma-exposed resilient controls) and repeated measures of plasma oxytocin and cortisol. Oxytocin and cortisol seemed reciprocal in all three groups, but both levels were relatively high in women with PTSD-D and low in those with PTSD compared with controls. This suggests that both hormones in women with PTSD-D and PTSD only are dysregulated, but not lacking in reciprocity.
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Affiliation(s)
- Yang Li
- University of Missouri Sinclair School of Nursing, Columbia, MO, 65211, USA.
| | - Afton L Hassett
- Department of Anesthesiology, University of Michigan Medical School, 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48106, USA
| | - Julia S Seng
- University of Michigan School of Nursing, 400 North Ingalls Street, Ann Arbor, MI, 48109, USA
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Dunlop BW, Wong A. The hypothalamic-pituitary-adrenal axis in PTSD: Pathophysiology and treatment interventions. Prog Neuropsychopharmacol Biol Psychiatry 2019; 89:361-379. [PMID: 30342071 DOI: 10.1016/j.pnpbp.2018.10.010] [Citation(s) in RCA: 128] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 10/15/2018] [Accepted: 10/16/2018] [Indexed: 12/26/2022]
Abstract
Questions of how altered functioning of the hypothalamic pituitary adrenal (HPA) axis contribute to the development and maintenance of posttraumatic stress disorder (PTSD) have been the focus of extensive animal and human research. As a rule, results have been inconsistent across studies, likely due to a variety of confounding variables that have received inadequate attention. Important confounding factors include the effects of early life stress, biological sex, and the glucocorticoid used for interventions. In this manuscript we review: 1) the literature on identified abnormalities of HPA axis function in PTSD, both in terms of basal functioning and as part of challenge paradigms; 2) the role of HPA axis function pre- and immediately post-trauma as a risk factor for PTSD development; 3) the impact of HPA axis genes' allelic variants and epigenetic modifications on PTSD risk; 4) the contributions of HPA axis components to fear learning and extinction; and 5) therapeutic manipulations of the HPA axis to both prevent and treat PTSD, including the role of glucocorticoids as part of medication enhanced psychotherapy.
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Affiliation(s)
- Boadie W Dunlop
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
| | - Andrea Wong
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
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Duesenberg M, Wolf OT, Metz S, Roepke S, Fleischer J, Elias V, Renneberg B, Otte C, Wingenfeld K. Psychophysiological stress response and memory in borderline personality disorder. Eur J Psychotraumatol 2019; 10:1568134. [PMID: 30788063 PMCID: PMC6374976 DOI: 10.1080/20008198.2019.1568134] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 11/29/2018] [Accepted: 12/29/2018] [Indexed: 10/27/2022] Open
Abstract
Background: Previously, we found that patients with borderline personality disorder (BPD) but not healthy controls (HC) showed improved memory retrieval after hydrocortisone administration. Objective: In this study, we examined whether increases in endogenous cortisol after psychosocial stress are associated with memory function in patients with BPD and in healthy individuals. Methods: We recruited 49 female patients with BPD and 49 female HC. All participants were exposed to a psychosocial stressor, the Trier Social Stress Test (TSST) and a control condition (Placebo (P-)TSST) in randomized order. Salivary cortisol, alpha amylase (sAA) and blood pressure were measured in response to stress. Subsequently, we examined free recall of a previously learned word list, autobiographical memory, and working memory. Results: We found a stress*time*group interaction effect for the cortisol response and for sAA to stress, which is mainly triggered by a slightly different increase in cortisol between groups from pre to post TSST. Furthermore, BPD patients showed a less pronounced increase in diastolic blood pressure compared to HC after stress. There was no effect of stress on memory performance in any tests, either in healthy controls or in patients with BPD. Conclusion: Our results suggest a slightly blunted response of the HPA axis and the sympathetic nervous system to stress in BPD compared to healthy women. In contrast to hydrocortisone administration, psychosocial stress did not improve memory retrieval in BPD patients. This might be explained by lower cortisol concentrations and parallel increases in norepinephrine and negative affect after stress.
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Affiliation(s)
- Moritz Duesenberg
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
| | - Oliver T Wolf
- Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr University Bochum, Bochum, Germany
| | - Sophie Metz
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
| | - Stefan Roepke
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
| | - Juliane Fleischer
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
| | - Valentina Elias
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
| | | | - Christian Otte
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
| | - Katja Wingenfeld
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Berlin, Germany
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Eswarappa M, Neylan TC, Whooley MA, Metzler TJ, Cohen BE. Inflammation as a predictor of disease course in posttraumatic stress disorder and depression: A prospective analysis from the Mind Your Heart Study. Brain Behav Immun 2019; 75:220-227. [PMID: 30389462 DOI: 10.1016/j.bbi.2018.10.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 10/01/2018] [Accepted: 10/29/2018] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Prior research has focused largely on the pro-inflammatory states of PTSD and depression, with few studies evaluating the direction of inflammation's association with these disorders. To clarify whether inflammation plays a role in the development of PTSD or depression, we assessed the predictive value of inflammatory biomarkers on the courses of these conditions in a cohort of Veterans. METHODS This research was part of the Mind Your Heart Study, a prospective cohort study designed to examine PTSD-related health outcomes. Between 2008 and 2010, 746 San Francisco area Veterans Administration patients were enrolled. At baseline, inflammatory biomarkers were measured from fasting morning venous blood draws, and cortisol and catecholamine levels were measured from 24-hour urine samples. PTSD was diagnosed using the PTSD Checklist at baseline and annual follow-up. Depression was evaluated using the 9-item Patient Health Questionnaire at baseline and follow-up. Ordinal logistic regression models were used to assess the predictive value of baseline biomarker levels on clinically relevant courses of PTSD and depression categorized and ordered as none, resolved, developed, and chronic. RESULTS After adjustment for age and sex, elevated levels of white blood cell count (OR = 1.27(1.10-1.47), p = 0.001), C-reactive protein (OR = 1.20(1.04-1.39), p = 0.02), fibrinogen (OR = 1.19(1.03-1.38), p = 0.02), and ESR (OR = 1.17(1.00-1.36, p = 0.05), and decreased levels of urine cortisol (OR = 0.84(0.71-0.99), p = 0.04) were significant predictors of poorer courses of PTSD. Elevated levels of WBC count (OR = 1.31(1.14-1.50), p < 0.001), CRP (OR = 1.24(1.07-1.43), p = 0.003), fibrinogen (OR = 1.26(1.09-1.46), p = 0.002), and catecholamines (OR = 1.17(1.01-1.36), p = 0.04) were significant predictors of poorer courses of depression. After additionally controlling for physical activity, elevated WBC count (p = 0.002) and decreased levels of urine cortisol (p = 0.05) remained significant predictors of PTSD course, and elevated WBC count (p = 0.001), CRP (p = 0.03), and fibrinogen (p = 0.02) remained significant predictors of depression course. After adjusting for all significant variables, elevated WBC count (p = 0.02) was a significant predictor of a poorer course of PTSD, and elevated WBC count (p = 0.04) and platelet count (p = 0.03) were significant predictors of a poorer course of depression. CONCLUSIONS Increased levels of several inflammatory biomarkers were associated with significantly increased odds of clinically worse courses of PTSD and depression. Inflammation may be a target for prevention and treatment of these mental health disorders.
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Affiliation(s)
| | - Thomas C Neylan
- Department of Psychiatry, University of California, San Francisco, CA, USA; Veterans Affairs Medical Center, San Francisco, CA, USA
| | - Mary A Whooley
- Department of Medicine, University of California, San Francisco, CA, USA; Veterans Affairs Medical Center, San Francisco, CA, USA
| | | | - Beth E Cohen
- Department of Medicine, University of California, San Francisco, CA, USA; Veterans Affairs Medical Center, San Francisco, CA, USA.
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Li Y, Seng JS. Child Maltreatment Trauma, Posttraumatic Stress Disorder, and Cortisol Levels in Women: A Literature Review. J Am Psychiatr Nurses Assoc 2018; 24:35-44. [PMID: 28569082 DOI: 10.1177/1078390317710313] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Studies of the relationship between cortisol and posttraumatic stress disorder (PTSD) have had inconsistent results. Gender, trauma type, and age at trauma exposure may explain the inconsistencies. OBJECTIVE The objective of the review was to examine cortisol levels in relation to PTSD in women with a history of child maltreatment trauma. DESIGN A review of literature found 13 articles eligible for inclusion. RESULTS Despite limiting focus to the relatively homogeneous population, the patterns of associations between PTSD and cortisol levels were still inconsistent. CONCLUSIONS The reasons for the inconsistencies likely include highly varied methods across studies, small convenience samples, and unmeasured neuroendocrine hormones that may be stronger predictors of PTSD. The review does not point to a clear bio-behavioral target for psychiatric nursing intervention. It is important to continue to address the developmental and clinical stress response aspects of child maltreatment trauma-related PTSD without assuming that these stress responses are hypothalamic-pituitary-adrenal-axis driven.
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Affiliation(s)
- Yang Li
- 1 Yang Li, BS, University of Michigan, Ann Arbor, MI, USA
| | - Julia S Seng
- 2 Julia S. Seng, PhD, CNM, University of Michigan, Ann Arbor, MI, USA
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Ewing-Cobbs L, Prasad MR, Cox CS, Granger DA, Duque G, Swank PR. Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms. Psychoneuroendocrinology 2017; 84:66-75. [PMID: 28667938 PMCID: PMC5555029 DOI: 10.1016/j.psyneuen.2017.06.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 05/22/2017] [Accepted: 06/08/2017] [Indexed: 12/14/2022]
Abstract
Injury is the leading cause of death and disability in childhood. Injured children are at high risk for developing alterations in stress response systems and post-traumatic stress symptoms (PTSS) that may compromise long-term physical and psychological health. In a prospective, observational cohort study, we examined individual differences in, and correlates of, stress-reactivity of the hypothalamic-pituitary-adrenal axis (HPA; salivary cortisol) and autonomic nervous system (ANS; salivary alpha amylase, sAA) following pediatric injury. Participants were 8-15 years of age and hospitalized for traumatic brain injury (TBI; n=55; M age=13.9 yrs; 40 males) or extracranial injury (EI; n=29; M age 12.3 yrs, 20 males) following vehicular accidents. Six months post-injury, saliva was collected before and after the Trier Social Stress Test and later assayed for cortisol and sAA. Relative to a healthy non-injured comparison group (n=33; M age=12.5 yrs, 16 males), injured children (ages 8-12 years), but not adolescents (ages 13-15 yrs), had higher cortisol levels; regardless of age, injured participants showed dampened cortisol reactivity to social evaluative threat. Compared to participants with EI, children with TBI had elevated cortisol and adolescents had elevated sAA. With respect to PTSS, individual differences in sAA were negatively correlated with avoidance in the TBI group and positively correlated with emotional numbing within the EI group. Importantly, psychological and neurobiological sequelae were weakly related to injury severity. Given the high prevalence of pediatric injury, these sequelae affect many children and represent a significant public health concern. Consequently, surveillance of post-traumatic sequelae should include the full spectrum of injury severity. Monitoring the activity, reactivity, and regulation of biological systems sensitive to environmental insults may advance our understanding of individual differences in sequelae and adaptation following traumatic pediatric injury.
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Affiliation(s)
- Linda Ewing-Cobbs
- Department of Pediatrics and Children's Learning Institute, University of Texas Health Science Center at Houston, United States.
| | - Mary R Prasad
- Department of Pediatrics and Children's Learning Institute, University of Texas Health Science Center at Houston, United States
| | - Charles S Cox
- Department of Pediatric Surgery, University of Texas Health Science Center at Houston, United States
| | - Douglas A Granger
- Department of Psychology and Social Behavior, Pediatrics, and Public Health and Institute for Interdisciplinary Salivary Bioscience, University of California Irvine, United States; School of Nursing, Bloomberg School of Public Health, and School of Medicine, Johns Hopkins University, United States
| | - Gerardo Duque
- Department of Pediatrics and Children's Learning Institute, University of Texas Health Science Center at Houston, United States
| | - Paul R Swank
- School of Public Health, University of Texas Health Science Center at Houston, United States
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Lee C, Coe CL, Ryff CD. Social Disadvantage, Severe Child Abuse, and Biological Profiles in Adulthood. JOURNAL OF HEALTH AND SOCIAL BEHAVIOR 2017; 58:371-386. [PMID: 29353512 PMCID: PMC5783196 DOI: 10.1177/0022146516685370] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Guided by the stress process model and the life course perspective, we hypothesize: (1) that childhood abuse is concentrated, in terms of type and intensity, among socially disadvantaged individuals, and (2) that experiencing serious abuse contributes to poor biological profiles in multiple body systems in adulthood. Data came from the Biomarker subsample of Midlife in the United States (2004-2006). We used latent class analysis to identify distinct profiles of childhood abuse, each reflecting a combination of type and severity. Results indicate that disadvantaged groups, women, and those from disadvantaged families are at greater risk of experiencing more severe and multiple types of abuse. Those with more severe and multifaceted childhood abuse show greater physiological dysregulation. Childhood abuse experiences partially accounted for the social status differences in physiological profiles. Our findings underscore that differential exposure to serious childhood stressors plays a significant role in gender and class inequalities in adult health.
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Affiliation(s)
- Chioun Lee
- 1 University of Wisconsin-Madison, Madison, WI, USA
| | | | - Carol D Ryff
- 1 University of Wisconsin-Madison, Madison, WI, USA
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Straub J, Klaubert LM, Schmiedgen S, Kirschbaum C, Goldbeck L. Hair cortisol in relation to acute and post-traumatic stress symptoms in children and adolescents. ANXIETY STRESS AND COPING 2017; 30:661-670. [PMID: 28745078 DOI: 10.1080/10615806.2017.1355458] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND We report on the preliminary results of two independent studies that (1) compare the hair cortisol concentrations (HCC) of healthy controls with patients displaying post-traumatic stress symptoms (PTSS, study 1+2), (2) investigate whether pre-trauma HCC are predictive for the development of acute stress symptoms (ASS) and PTSS (study 1) and (3) determine whether HCC correlate with PTSS in a clinical sample of children (study 2). METHODS In study 1, the clinical symptoms of 35 minors were examined one (T1) and seven weeks (T2) after surgery following an accident. Hair samples were taken after the accident that reflect cortisol secretion over the past three months before the accident (healthy controls). In study 2, HCC and PTSS symptoms were cross-sectionally assessed in 22 minors who had experienced a psychological trauma. RESULTS The HCC of patients with PTSS were lower than the HCC of healthy controls (study 1+2). Secondary analyses showed that HCC were significantly lower in male PTSS patients than in male healthy controls, whereas the HCC in females were comparably low in both groups. Pre-trauma HCC did not predict the total ASS and PTSS scores (study 1) and HCC were not directly related to the total PTSS scores (study 2).
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Affiliation(s)
- Joana Straub
- a Department of Child and Adolescent Psychiatry and Psychotherapy , University of Ulm , Ulm , Germany
| | - Lena Marie Klaubert
- a Department of Child and Adolescent Psychiatry and Psychotherapy , University of Ulm , Ulm , Germany
| | - Susann Schmiedgen
- b Institute of Biological Psychology, Technische Universität Dresden , Dresden , Germany
| | - Clemens Kirschbaum
- b Institute of Biological Psychology, Technische Universität Dresden , Dresden , Germany
| | - Lutz Goldbeck
- a Department of Child and Adolescent Psychiatry and Psychotherapy , University of Ulm , Ulm , Germany
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Affiliation(s)
- Arieh Shalev
- From the Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and TBI, Department of Psychiatry, New York University School of Medicine, New York (A.S., C.M.); and the Department of Psychiatry, University of Michigan, and the Mental Health Service, Veterans Affairs Ann Arbor Health Systems - both in Ann Arbor (I.L.)
| | - Israel Liberzon
- From the Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and TBI, Department of Psychiatry, New York University School of Medicine, New York (A.S., C.M.); and the Department of Psychiatry, University of Michigan, and the Mental Health Service, Veterans Affairs Ann Arbor Health Systems - both in Ann Arbor (I.L.)
| | - Charles Marmar
- From the Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and TBI, Department of Psychiatry, New York University School of Medicine, New York (A.S., C.M.); and the Department of Psychiatry, University of Michigan, and the Mental Health Service, Veterans Affairs Ann Arbor Health Systems - both in Ann Arbor (I.L.)
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Bandelow B, Baldwin D, Abelli M, Bolea-Alamanac B, Bourin M, Chamberlain SR, Cinosi E, Davies S, Domschke K, Fineberg N, Grünblatt E, Jarema M, Kim YK, Maron E, Masdrakis V, Mikova O, Nutt D, Pallanti S, Pini S, Ströhle A, Thibaut F, Vaghix MM, Won E, Wedekind D, Wichniak A, Woolley J, Zwanzger P, Riederer P. Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition. World J Biol Psychiatry 2017; 18:162-214. [PMID: 27419272 PMCID: PMC5341771 DOI: 10.1080/15622975.2016.1190867] [Citation(s) in RCA: 190] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 05/03/2016] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). METHODS Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. RESULTS The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics. CONCLUSIONS Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.
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Affiliation(s)
- Borwin Bandelow
- Department of Psychiatry and Psychotherapy, University of Göttingen, Germany
| | - David Baldwin
- Faculty of Medicine, University of Southampton, Southampton, UK
| | - Marianna Abelli
- Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Pisa, Italy
| | - Blanca Bolea-Alamanac
- School of Social and Community Medicine, Academic Unit of Psychiatry, University of Bristol, Bristol, UK
| | - Michel Bourin
- Neurobiology of Anxiety and Mood Disorders, University of Nantes, Nantes, France
| | - Samuel R. Chamberlain
- Hertfordshire Partnership University NHS Foundation Trust and University of Hertfordshire, Parkway, UK
- Department of Psychiatry, University of Cambridge, Cambridge, UK
| | - Eduardo Cinosi
- Department of Neuroscience Imaging and Clinical Sciences, Gabriele D’Annunzio University, Chieti, Italy
| | - Simon Davies
- Centre for Addiction and Mental Health, Geriatric Psychiatry Division, University of Toronto, Toronto, Canada
- School of Social and Community Medicine, Academic Unit of Psychiatry, University of Bristol, Bristol, UK
| | - Katharina Domschke
- Department of Psychiatry Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Naomi Fineberg
- Hertfordshire Partnership University NHS Foundation Trust and University of Hertfordshire, Parkway, UK
| | - Edna Grünblatt
- Department of Psychiatry Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
- Neuroscience Center Zurich, University of Zurich and the ETH Zurich, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - Marek Jarema
- Third Department of Psychiatry, Institute of Psychiatry and Neurology, Warszawa, Poland
| | - Yong-Ku Kim
- Department of Psychiatry College of Medicine, Korea University, Seoul, Republic of Korea
| | - Eduard Maron
- Department of Psychiatry, North Estonia Medical Centre, Tallinn, Estonia
- Department of Psychiatry, University of Tartu, Estonia
- Faculty of Medicine Department of Medicine, Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK
| | - Vasileios Masdrakis
- Athens University Medical School, First Department of Psychiatry, Eginition Hospital, Athens, Greece
| | - Olya Mikova
- Foundation Biological Psychiatry, Sofia, Bulgaria
| | - David Nutt
- Faculty of Medicine Department of Medicine, Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK
| | - Stefano Pallanti
- UC Davis Department of Psychiatry and Behavioural Sciences, Sacramento, CA, USA
| | - Stefano Pini
- Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Pisa, Italy
| | - Andreas Ströhle
- Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité – University Medica Center Berlin, Berlin, Germany
| | - Florence Thibaut
- Faculty of Medicine Paris Descartes, University Hospital Cochin, Paris, France
| | - Matilde M. Vaghix
- Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK
| | - Eunsoo Won
- Department of Psychiatry College of Medicine, Korea University, Seoul, Republic of Korea
| | - Dirk Wedekind
- Department of Psychiatry and Psychotherapy, University of Göttingen, Germany
| | - Adam Wichniak
- Third Department of Psychiatry, Institute of Psychiatry and Neurology, Warszawa, Poland
| | - Jade Woolley
- Faculty of Medicine, University of Southampton, Southampton, UK
| | - Peter Zwanzger
- kbo-Inn-Salzach-Klinikum Wasserburg am Inn, Germany
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany
| | - Peter Riederer
- Department of Psychiatry Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
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Stress hormones and posttraumatic stress symptoms following paediatric critical illness: an exploratory study. Eur Child Adolesc Psychiatry 2017; 26:511-519. [PMID: 27995329 PMCID: PMC5394132 DOI: 10.1007/s00787-016-0933-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Accepted: 12/07/2016] [Indexed: 12/04/2022]
Abstract
In this exploratory case-control study, we investigated basal cortisol regulation in 5-16-year-old children, 3-6 months following PICU (paediatric intensive care) admission. This was nested within a study of child psychological and cognitive function; 47 children were assessed alongside 56 healthy controls. Saliva samples were collected three times per day (immediately after waking, waking +30 min, and waking +12 h) over two consecutive weekdays. In addition, data on posttraumatic stress symptoms were ascertained from 33 PICU admitted children using the Impact of Events Scale-8 (IES-8). Primary analysis revealed no significant differences in basal cortisol concentrations between PICU discharged children and healthy controls (p > 0.05). Secondary analysis in the PICU group identified a significant positive association between posttraumatic stress symptoms and evening (waking +12 h) cortisol concentrations (p = 0.004). However, when subject to multivariate analysis, evening cortisol was a modest independent predictor of IES-8 scores, relative to the presence of septic illness and poor pre-morbid health. We conclude that paediatric critical illness does not appear to result in marked perturbations to basal cortisol at 3-6 month following discharge. There was evidence of a link between evening cortisol and symptoms of PTSD, but this was not a robust effect and requires further elucidation.
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Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology 2017; 42:254-270. [PMID: 27510423 PMCID: PMC5143487 DOI: 10.1038/npp.2016.146] [Citation(s) in RCA: 457] [Impact Index Per Article: 57.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 07/01/2016] [Accepted: 07/12/2016] [Indexed: 02/07/2023]
Abstract
The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.
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Steffen PR, Austin T, DeBarros A. Treating Chronic Stress to Address the Growing Problem of Depression and Anxiety. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/2372732216685333] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Depression and anxiety are undertreated and represent a growing health crisis and economic burden. Current treatment approaches (medications, psychotherapy) appear insufficient to resolve these problems. Difficulties with current treatment approaches include cost, side effects, and stigma. Given that depression and anxiety share significant features and a common etiology in chronic stress, an effective approach to reduce depression and anxiety may be to reduce chronic stress. Chronic stress is on the rise, with more than one third of Americans reporting high levels of stress with which they feel they cannot adequately cope. Treating chronic stress at the population level has the potential to reduce the rising tide of depression and anxiety. Biofeedback and mindfulness are two interventions that demonstrably reduce stress and negative mood, are cost and time-effective, have no side effects, and have minimal stigma relative to medications and psychotherapy.
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Rombold F, Wingenfeld K, Renneberg B, Schwarzkopf F, Hellmann-Regen J, Otte C, Roepke S. Impact of exogenous cortisol on the formation of intrusive memories in healthy women. J Psychiatr Res 2016; 83:71-78. [PMID: 27569651 DOI: 10.1016/j.jpsychires.2016.08.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 07/28/2016] [Accepted: 08/05/2016] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Stress hormones such as cortisol are involved in modulating emotional memory. However, little is known about the influence of cortisol on the formation of intrusive memories after a traumatic event. The aim of this study was to examine whether cortisol levels during encoding and consolidation of an intrusion-inducing trauma film paradigm would influence subsequent intrusion formation. MATERIAL AND METHODS In an experimental, double-blind, placebo-controlled study a trauma film paradigm was used to induce intrusions in 60 healthy women. Participants received a single dose of either 20 mg hydrocortisone or placebo before watching a trauma film. Salivary cortisol and alpha-amylase as well as blood pressure were measured during the experiment. The consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions resulting from the trauma film were assessed throughout the following seven days. RESULTS Hydrocortisone administration before the trauma film resulted in increased salivary cortisol levels but did not affect the consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions throughout the following week. CONCLUSIONS These results indicate that pharmacologically increased cortisol levels during an experimental trauma film paradigm do not influence consecutive intrusive memories. Current data do not support a prominent role of exogenous cortisol on intrusive memories, at least in healthy young women after a relatively mild trauma equivalent.
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Affiliation(s)
- Felicitas Rombold
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; Department of Psychology, Freie Universität Berlin, Germany.
| | - Katja Wingenfeld
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | | | - Friederike Schwarzkopf
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Julian Hellmann-Regen
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Christian Otte
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Stefan Roepke
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
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Gilpin NW, Weiner JL. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder. GENES BRAIN AND BEHAVIOR 2016; 16:15-43. [PMID: 27749004 DOI: 10.1111/gbb.12349] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 10/03/2016] [Accepted: 10/07/2016] [Indexed: 12/12/2022]
Abstract
Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.
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Affiliation(s)
- N W Gilpin
- Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA.,Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA
| | - J L Weiner
- Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Morris MC, Hellman N, Abelson JL, Rao U. Cortisol, heart rate, and blood pressure as early markers of PTSD risk: A systematic review and meta-analysis. Clin Psychol Rev 2016; 49:79-91. [PMID: 27623149 PMCID: PMC5079809 DOI: 10.1016/j.cpr.2016.09.001] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 07/27/2016] [Accepted: 09/02/2016] [Indexed: 11/28/2022]
Abstract
Individuals with posttraumatic stress disorder (PTSD) typically exhibit altered hypothalamic-pituitary-adrenal (HPA) function and sympathetic nervous system (SNS) activity. The goals of this study were to determine whether HPA and SNS alterations in the immediate aftermath of trauma predict subsequent PTSD symptom development and whether inconsistencies observed between studies can be explained by key demographic and methodological factors. This work informs secondary prevention of PTSD by identifying subgroups of trauma survivors at risk for PTSD. This meta-analysis (26 studies, N=5186 individuals) revealed that higher heart rate measured soon after trauma exposure was associated with higher PTSD symptoms subsequently (r=0.13). Neither cortisol (r=-0.07) nor blood pressure (diastolic: r=-0.01; systolic: r=0.02) were associated with PTSD symptoms which may be influenced by methodological limitations. Associations between risk markers (heart rate, cortisol, systolic blood pressure) and PTSD symptoms were in the positive direction for younger samples and negative direction for older samples. These findings extend developmental traumatology models of PTSD by revealing an age-related shift in the presentation of early risk markers. More work will be needed to identify risk markers and pathways to PTSD while addressing methodological limitations in order to shape and target preventive interventions.
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Affiliation(s)
- Matthew C Morris
- Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, United States; Center for Molecular and Behavioral Neuroscience, Meharry Medical College, Nashville, TN, United States; Department of Psychology, Vanderbilt University, Nashville, TN, United States.
| | - Natalie Hellman
- Department of Psychology, The University of Tulsa, Tulsa, OK, United States
| | - James L Abelson
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States
| | - Uma Rao
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, United States; Center for Behavioral Health Research, University of Tennessee, Knoxville, TN, United States
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Zuj DV, Palmer MA, Lommen MJJ, Felmingham KL. The centrality of fear extinction in linking risk factors to PTSD: A narrative review. Neurosci Biobehav Rev 2016; 69:15-35. [PMID: 27461912 DOI: 10.1016/j.neubiorev.2016.07.014] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 07/13/2016] [Accepted: 07/14/2016] [Indexed: 02/08/2023]
Abstract
Recent prospective studies in emergency services have identified impaired fear extinction learning and memory to be a significant predictor of Posttraumatic Stress Disorder (PTSD), complementing a wealth of cross-sectional evidence of extinction deficits associated with the disorder. Additional fields of research show specific risk factors and biomarkers of the disorder, including candidate genotypes, stress and sex hormones, cognitive factors, and sleep disturbances. Studies in mostly nonclinical populations also reveal that the aforementioned factors are involved in fear extinction learning and memory. Here, we provide a comprehensive narrative review of the literature linking PTSD to these risk factors, and linking these risk factors to impaired fear extinction. On balance, the evidence suggests that fear extinction may play a role in the relationship between risk factors and PTSD. Should this notion hold true, this review carries important implications for the improvement of exposure-based treatments, as well as strategies for the implementation of treatment.
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Affiliation(s)
- Daniel V Zuj
- Division of Psychology, School of Medicine, University of Tasmania, Tasmania, Australia.
| | - Matthew A Palmer
- Division of Psychology, School of Medicine, University of Tasmania, Tasmania, Australia
| | - Miriam J J Lommen
- Department of Psychology, University of Groningen, Groningen, The Netherlands
| | - Kim L Felmingham
- Division of Psychology, School of Medicine, University of Tasmania, Tasmania, Australia
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