Psychoneuroimmunology (PNI), also referred to as psychoendoneuroimmunology (PENI) or psychoneuroendocrinoimmunology (PNEI), is the study of the interaction between psychological processes and the nervous and immune systems of the human body. It is a subfield of psychosomatic medicine. PNI takes an interdisciplinary approach, incorporating psychology, neuroscience, immunology, physiology, genetics, pharmacology, molecular biology, psychiatry, behavioral medicine, infectious diseases, endocrinology, and rheumatology.
The main interests of PNI are the interactions between the nervous and immune systems and the relationships between mental processes and health. PNI studies, among other things, the physiological functioning of the neuroimmune system in health and disease; disorders of the neuroimmune system (autoimmune diseases; hypersensitivities; immune deficiency); and the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro, in situ, and in vivo.
It is now clear that the cellular and molecular processes that make up our ‘immune system’ are also crucial to normal brain development and play a role in the pathoaetiology of many mental and physical disorders.
Troyer, E. A., Kohn, J. N., & Hong, S.. (2020). Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain, Behavior, and Immunity, 87, 34–39.
“The coronavirus disease 19 (covid-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals’ lives and organizations in virtually all social and economic sectors worldwide. fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. however, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; sars-cov-2), and the subsequent host immunologic response, on the human central nervous system (cns) and related outcomes are unknown. we discuss currently available evidence of covid-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. the potential mechanisms are also discussed, including viral and immunological underpinnings. therefore, prospective neuropsychiatric monitoring of individuals exposed to sars-cov-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of covid-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.”
Hamilton-West, K.. (2011). Psychobiological Processes in Health and Illness. Psychobiological Processes in Health and Illness. 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP United Kingdom: SAGE Publications Ltd
“Psychobiological processes in health and illness is an accessible and engaging introduction to the interrelationships between mind and body across a broad range of topics including infectious illness, autoimmunity, cancer and pain. taking a biopsychosocial approach, it brings together research from a number of disciplines including health psychology, psychoneuroimmunology and behavioral genetics. the textbook presents established theoretical models relevant to psychobiological processes in health and illness, as well as recent developments in systems, technologies and intervention methods.”
Mravec, B., Tibensky, M., & Horvathova, L.. (2020). Stress and cancer. Part II: Therapeutic implications for oncology. Journal of Neuroimmunology, 346, 577312.
“Accumulated evidence has confirmed the ability of stress to promote the induction and progression of cancer (for review see stress and cancer. part i: mechanisms mediating the effect of stressors on cancer). in support of this, data from clinical trials utilizing approaches that reduce stress-related signaling have shown prolonged survival of cancer patients. therefore, the question has arisen as to how we can utilize this knowledge in the daily treatment of cancer patients. the main aim of this review is to critically analyze data from studies utilizing psychotherapy or treatment by β-blockers on the survival of cancer patients. because these approaches, especially treatment by β-blockers, have been routinely used in clinical practice for decades in the treatment of non-cancer patients, their wider introduction into oncology might be realized in the near future.”
Pahlevi, R., Putra, S. T., & Sriyono, S.. (2017). Psychoneuroimmunology Approach to Improve Recovery Motivation, Decrease Cortisol and Blood Glucose of DM Type 2 Patients with Dhikr Therapy. Jurnal Ners, 12(1), 60–65.
“Introduction: blood glucose levels are controlled when the management of diabetes success. positive perception of the strength of the spiritual aspect will improve the motivation of patients with type 2 diabetes to control it. the purpose of this study was to determine the effect of dhikr based on psychoneuroimmunology (pni) on blood glucose levels of patients with type 2 diabetes.methods: this study used quasi-experiment with pre-test and post-test control group design. samples were taken from the population of patients with type 2 diabetes who were hospitalized in the internal medicine rumkital dr. ramelan surabaya with purposive sampling techniques. data taken include the general characteristics of respondents, cures motivation, cortisol levels and fasting blood glucose levels. collecting data using questionnaires and laboratory test, then analyzed using paired t-test and independent t-test, with α value <0.05.results: statistical test showed that the motivation to recover increased (p = 0.001), cortisol levels fall (p = 0.058) and a drop in blood glucose levels (p = 0.028) after administration of dhikr therapy in patients with diabetes mellitus type 2. there was a significant difference in increased of recovery motivation between patient conduct zikr therapy and patient cared (p = 0,000).conclusion: dhikr therapy increases the motivation of patients with type 2 diabetes by strengthening awareness and spirituality belief in allah make positive stress perception. positive stress perception will affect the stress response and improved regulation of blood glucose through the hpa axis to suppress the secretion of crh, acth, and cortisol.”
Mathews, H. L., & Janusek, L. W.. (2011). Epigenetics and psychoneuroimmunology: Mechanisms and models. Brain, Behavior, and Immunity, 25(1), 25–39.
Labanski, A., Langhorst, J., Engler, H., & Elsenbruch, S.. (2020). Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology, 111, 104501.
“The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. these include the functional gastrointestinal disorders (fgid), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (ibd) like ulcerative colitis and crohn’s disease. although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (pne)/ psychoneuroimmunology (pni) remain only loosely connected. we aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. to this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of fgids and ibd. from an interdisciplinary pne/pni perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of fgid and ibd. we provide an overview of evidence regarding non-pharmacological treatment approaches that target central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.”
Leckman, J. F.. (2014). Commentary: What does immunology have to do with brain development and psychopathology? – A commentary on O’Connor et al. (2014). Journal of Child Psychology and Psychiatry and Allied Disciplines
“Worry, the cognitive enumeration and anticipation of potential future negative events, is associated with autonomic dysregulation, which may in turn have implications for the immune system. people endorsing high (n = 7) and normal levels of trait worry (n = 8) were briefly exposed to a phobic stimulus and the autonomic and immune responses and recovery were assessed. a time-matched control group (n = 6) was not exposed to any stimulus. both worry groups showed increased heart rate and skin conductance in response to phobic fear. however, only the normal worry group showed a concomitant increase in natural killer cells in peripheral blood. patterns of change during the follow-up period suggested that phobic fear had disrupted a normal circadian increase in natural killer cells. adrenergic and hypothalamus-pituitary-adrenal mechanisms may be responsible for the differences between high and normal worry groups in their natural killer cell response to and recovery from phobic fear.”
Aziez Chettoum, Kamilia Guedri, Zouhir Djerrou, Rachid Mosbah, Latifa Khattabi, Abir Boumaaza, & Wissam Benferdi. (2020). Distribution of leukocyte subpopulation among students threatened by failure. International Journal of Research in Pharmaceutical Sciences, 11(3), 3807–3812.
“Psychoneuroimmunology or the study of the relationships between the brain and the immune system is an area of research that has experienced significant development over the decade. stress does not appear without consequences on the state of health, the role of fears, emotions and significant constraints in the appearance of organic and mental diseases. in this research, we studied the effect of stress and anxiety during exams at the end of the academic year (2018/2019) on the distribution of leukocyte subpopulations and the immune system, questionnaires has been completed by student volunteers, to estimate the anxio-depressive comorbidities through the (hads) test during and outside exams, and in the same time we asked them for a blood sample the next morning day to carry out some biological assays (cbc). we also found that stress during exams caused a change in the distribution of different types of white blood cells, a total decrease in white blood cell counts with neutropenia and lymphopenia were found in students during exams compared to controls, and an increase in monocyte and other types of polymorphonuclear levels in students during exams compared to controls. other tests measuring the effects of stress on specific functions of the immune system can be used.”
Dr. Kary Mullis, Biochemist, 1993 Nobel Prize for Chemistry: Dr. Kary Mullis “If there is evidence that HIV causes AIDS, there should be scientific documents which either singly or collectively demonstrate that fact, at least with a high probability. There is no such document.” (Sunday Times (London) 28 nov. 1993) Dr. Heinz Ludwig Sanger, Emeritus Professor of Molecular Biology and Virology, Max-Planck-Institutes for Biochemy, Munchen. Robert Koch Award 1978: “Up to today there is actually no single scientifically really convincing evidence for the existence of HIV. Not even once such a retrovirus has been isolated and purified by the methods of classical virology.” (Letter to Suddeutsche Zeitung 2000) Dr. Serge Lang, Professor of Mathematics, Yale University: “I do not regard the causal relationship between HIV and any disease as settled. I have seen considerable evidence that highly improper statistics concerning HIV and AIDS have been passed off as science, and that top members of the scientific establishment have carelessly, if not irresponsible, joined the media in spreading misinformation about the nature of AIDS.” (Yale Scientific, Fall 1994) Dr. Harry Rubin, Professor of Molecular and Cell Biology, University of California at Berkeley: Prof. Harry Rubin “It is not proven that AIDS is caused by HIV infection, nor is it proven that it plays no role whatever in the syndrome.” (Sunday Times (London) 3 April 1994) Dr. Richard Strohman, Emeritus Professor of Cell Biology at the University of California at Berkeley: “In the old days it was required that a scientist address the possibilities of proving his hypothesis wrong as well as right. Now there’s none of that in standard HIV-AIDS program with all its billions of dollars.” (Penthouse April 1994) Dr. Harvey Bialy, Molecular Biologist, former editor of Bio/Technology and Nature Biotechnology: Harvey Bialy “HIV is an ordinary retrovirus. There is nothing about this virus that is unique. Everything that is discovered about HIV has an analogue in other retroviruses that don’t cause AIDS. HIV only contains a very small piece of genetic information. There’s no way it can do all these elaborate things they say it does.” (Spin June 1992) Dr. Roger Cunningham, Immunologist, Microbiologist and Director of the Centre for Immunology at the State University of New York at Buffalo: “Unfortunately, an AIDS ‘establishment’ seems to have formed that intends to discourage challenges to the dogma on one side and often insists on following discredited ideas on the other.” (Sunday Times (London) 3 April 1994) Dr. Gordon Stewart, Emeritus Professor of Public Health, University of Glasgow: Prof. Gordon Stwart “AIDS is a behavioural disease. It is multifactorial, brought on by several simultaneous strains on the immune system – drugs, pharmaceutical and recreational, sexually transmitted diseases, multiple viral infections.” (Spin June 1992) Dr. Alfred Hassig, (1921-1999), former Professor of Immunology at the University of Bern, and former director Swiss Red Cross blood banks: Prof. Alfred Hassig “The sentence of death accompanying the medical diagnosis of AIDS should be abolished.” (Sunday Times (London) 3 April 1994) Dr. Charles Thomas, former Professor of Biochemistry, Harvard and John Hopkins Universities: “The HIV-causes-AIDS dogma represents the grandest and perhaps the most morally destructive fraud that has ever been perpetrated on young men and women of the Western world.” (Sunday Times (London) 3 April 1994) Dr. Joseph Sonnabend, New York Physician, founder of the American Foundation for AIDS Research (AmFAR): Joe Sonnabend “The marketing of HIV, through press releases and statements, as a killer virus causing AIDS without the need for any other factors, has so distorted research and treatment that it may have caused thousands of people to suffer and die.”
“El desarrollo de la biología molecular y la genética ha sido posible gracias al trabajo multidisci-plinario de muchas personas, en este blog quiero resaltar el trabajo del dr. kary banks mullis, el cual se considera el padre de la técnica de la reacción en cadena de la polimerasa, o mejor conocido como pcr, protocolo que utilizamos diariamente en nuestras investigaciones y que tiene grandes aplicaciones médicas e industriales. el dr. mullis, obtuvo su grado de licenciatura en ciencias (química) en el instituto de tecnología de georgia en 1966. en 1973 obtiene su título de doctorado en bioquímica en la universidad de berkeley. en 1979, se une a una de las primeras compañías en biotecnología lla-mada cetus en california, años después desarrolla (junto a un equipo de trabajo) la síntesis de oligonucleótidos y la pcr. gracias a este ‘momento eureka’ inicia la revolución de la biología molecular, tanto a nivel de investigación como con toda la industria de equipos y consumibles que requiere. debido a este aporte tan significativo, recibe en 1993 el premio nobel en quími-ca, galardón que compartió con michael smith, quien lo recibió por sus investigaciones en mu-tagénesis dirigida basada en oligonucleótidos y su desarrollo para estudios de proteínas. a pesar de que se considera uno de los descubrimientos más importantes a nivel cientí-fico del siglo xx, al principio contó con una serie de inconvenientes o algunas preocupaciones sobre el funcionamiento de la técnica. en su página personal, el dr. mullis describe al menos cuatro de los posibles problemas que enfrentaría su gran idea, sin embargo el más importante por resolver era la enzima que utilizaría para lograrlo, ya que debía ser funcional a altas tem-peraturas. cabe resaltar que la idea contemplaba el uso de ciclos de elevadas temperaturas (50°c a 95°c) para lograr abrir la hebra de adn y poder amplificar la región de interés, y que por ende el procedimiento debía ser llevado en un baño maría (en ese momento no habían termocicladores). en 1988, junto a r. k. saiki y colaboradores, describe el uso de una enzima polimerasa termoestable, la polimerasa taq, aislada de la bacteria thermus aquaticus (obtenida de fuentes termales), la cual se puede utilizar a altas temperaturas. este último hallazgo junto a la técnica de pcr revolucionaron todos los conocimientos de genética y biología molecular que se tenían hasta el momento, siguen siendo muy útiles hoy en día y son la base de otras técnicas y protocolos ampl…”
Galibert, F., & Netter, P.. (2021). Hommage à Kary Mullis. Bulletin de l’Académie Nationale de Médecine, 205(4), 383–386.
“The article highlights the major life and career milestones and the extraordinary personality of 1993 nobel prize laureate in chemistry kary b. mullis. the background of mullis’ invention of the polyme-rase chain reaction (pcr), a revolutionary and monumental method of molecular biology and genetics of the 20th century, is described. the pcr technique is based on multiple selective copying of a particular segment of dna with the help of enzymes in vitro. under these conditions, only the target region is copied, and only if it is present in the studied sample. the invention of the pcr method has been one of the most outstanding events in molecular biology in recent decades.”
Pfefferbaum, B., Nitiéma, P., & Newman, E.. (2019). A Meta-analysis of Intervention Effects on Depression and/or Anxiety in Youth Exposed to Political Violence or Natural Disasters. Child and Youth Care Forum
“Background: meta-analyses of youth mass trauma intervention studies have focused primarily on posttraumatic stress even though depression and anxiety are common maladaptive outcomes that require intervention. objective: this meta-analysis examined youth mass trauma intervention effects on depression and anxiety relative to natural recovery and characteristics of the event, context, population, intervention, and intervention delivery that may have moderated these effects. method: a literature search identified 21 studies investigating the effectiveness of 24 randomized controlled trials with inactive controls (21 trials examined depression and 8 examined anxiety; 5 examined both). intervention effects were computed as hedge’s g estimates and combined using random effects models. moderator analysis computed intervention effect sizes across selected covariates. results: the summary intervention effect was not significant for either depression or anxiety. there were statistically significant effects for depression with interventions delivered following a natural disaster (g = 0.40; p = 0.0192) or in a high income country (g = 0.30; p = 0.0253) and with non-trauma-focused interventions (g = 0.29; p = 0.0155) and those delivered in more than eight sessions (g = 0.23; p = 0.0416). the effect for anxiety symptoms was significant only with non-trauma-focused interventions (g = 0.83; p = 0.0428). conclusions: given the prevalence of depression and anxiety post event, greater attention is warranted to develop and maximize the benefit of interventions for these outcomes. the findings suggest that trauma-focused interventions may need to be augmented with specific components directed at depression and/or anxiety.”
Pfefferbaum, B., Noffsinger, M. A., & Wind, L. H.. (2012). Issues in the assessment of Children’s coping in the context of mass trauma. Prehospital and Disaster Medicine
“Over the last 20 years, numerous interventions have been developed and evaluated for use with children exposed to mass trauma with six publications reporting meta-analyses of randomized controlled trials of child mass trauma interventions using inactive controls to examine intervention effects on posttraumatic stress, depression, anxiety, and functional impairment. the current report reviews the results of these meta-analytic studies to examine the status of the evidence for child mass trauma mental health interventions and to evaluate potential moderators of intervention effect and implications for practice. the meta-analyses reviewed for the current report revealed a small to medium overall effect of interventions on posttraumatic stress, a non-statistically significant to small overall effect on depression, a non-statistically significant overall effect on anxiety, and a small overall effect on functional impairment. the subgroup analyses suggest that interventions should be matched to the populations being served and to the context. additional research is needed to tailor future interventions to further address outcomes other than posttraumatic stress including depression, anxiety, and functional impairment.”
Pfefferbaum, B., Nitiéma, P., & Newman, E.. (2020). The Effect of Interventions on Functional Impairment in Youth Exposed to Mass Trauma: a Meta-Analysis. Journal of Child and Adolescent Trauma
“This study examined the benefit of psychosocial interventions on functional impairment in youth exposed to mass trauma. a random effects meta-analysis was used to estimate the overall effect in 15 intervention trials identified through a literature review. the moderator analysis examined how the effect of intervention differed across types of populations receiving the intervention (targeted or non-targeted samples), characteristics of intervention delivery (individual or group application and number of sessions), and the context of intervention administration (country income level). the results revealed a significant small effect on functional impairment (hedges’ g = 0.33; 95%ci = (0.16; 0.50); p = 0.0011). none of the moderators explained the heterogeneity in intervention effect, perhaps due to the small number of trials. the effect of the interventions on functional impairment and on posttraumatic stress were positively correlated. the current analysis provides preliminary evidence that interventions can improve functioning in youth exposed to mass trauma, but the mechanisms, moderators, and duration of benefit are yet unknown.”
Pfefferbaum, B., Nitiéma, P., Newman, E., & Patel, A.. (2019). The Benefit of Interventions to Reduce Posttraumatic Stress in Youth Exposed to Mass Trauma: A Review and Meta-Analysis. Prehospital and Disaster Medicine
“Numerous interventions to address posttraumatic stress (pts) in youth exposed to mass trauma have been delivered and evaluated. it remains unclear, however, which interventions work for whom and under what conditions. this report describes a meta-analysis of the effect of youth mass-trauma interventions on pts to determine if interventions were superior to inactive controls and describes a moderator analysis to examine whether the type of event, population characteristics, or income level of the country where the intervention was delivered may have affected the observed effect sizes. a comprehensive literature search identified randomized controlled trials (rcts) of youth mass-trauma interventions relative to inactive controls. the search identified 2,232 references, of which 25 rcts examining 27 trials (n = 4,662 participants) were included in this meta-analysis. intervention effects were computed as hedge’s g estimates and combined using a random effects model. moderator analyses were conducted to explain the observed heterogeneity among effect sizes using the following independent variables: disaster type (political violence versus natural disaster); sample type (targeted versus non-targeted); and income level of the country where the intervention was delivered (high-versus middle-versus low-income). the correlation between the estimates of the intervention effects on pts and on functional impairment was estimated. the overall treatment effect size was converted into a number needed to treat (nnt) for a practical interpretation. the overall intervention effect was statistically significant (g = 0.57; p <.0001), indicating that interventions had a medium beneficial effect on pts. none of the hypothesized moderators explained the heterogeneity among the intervention effects. estimates of the intervention effects on pts and on functional impairment were positively correlated (spearman’s r = 0.90; p <.0001), indicating a concomitant improvement in both outcomes. these findings confirm that interventions can alleviate pts and enhance functioning in children exposed to mass trauma. this study extends prior research by demonstrating improvement in pts with interventions delivered to targeted and non-targeted populations, regardless of the country income level. intervention populations and available resources should be considered when interpreting the results of intervention studies to inform recommendations for practice.”
Tarvydas, V. M., Levers, L. L., & Teahen, P. R.. (2017). Ethical Guidelines for Mass Trauma and Complex Humanitarian Emergencies. Journal of Counseling and Development
“Issues pertaining to trauma, especially mass trauma and complex humanitarian emergencies, are explored through the lens of ethical counseling guidelines. in mass trauma, particular attention must be paid to the experiences of both survivors and counselors to enhance understanding of ethical best practices and to emphasize the importance of contextual factors in framing effective responses to trauma and humanitarian crises. recommendations regarding ethical guidelines for counseling practice, clinical involvement, and training are offered.”
Pfefferbaum, B., Tucker, P., Nitiéma, P., Van Horn, R. L., Varma, V., Varma, Y., … Newman, E.. (2022). Inconclusive Findings in Studies of the Link Between Media Coverage of Mass Trauma and Depression in Children. Current Psychiatry Reports
“Purpose of review: this paper reports a review of the empirical research examining the association between mass trauma media contact and depression in children, the factors that may influence the association, and the difficulties encountered in the study of media effects on depression. recent findings: all of the included studies assessed general population samples. pre-covid-19 research focused primarily on television coverage alone or on multiple media forms including television, while covid-19 media studies examined various media forms including social media. most studies used cross-sectional design and non-probability sampling. the review revealed inconclusive findings across studies. summary: the study of mass trauma media effects on depression in children is complicated by a number of potential confounding factors and by the relatively high prevalence of depression in the general population. media contact was a relatively minor consideration among other interests in the extant studies which failed to explore numerous issues that warrant attention in future research.”
Meffert, S., & Ekblad, S.. (2013). Global mental health intervention research and mass trauma. Open Access Journal of Clinical Trials
Hobfoll, S. E., Watson, P., Bell, C. C., Bryant, R. A., Brymer, M. J., Friedman, M. J., … Ursano, R. J.. (2007). Five essential elements of immediate and mid-term mass trauma intervention: Empirical evidence. Psychiatry
“Given the devastation caused by disasters and mass violence, it is critical that intervention policy be based on the most updated research findings. however, to date, no evidence-based consensus has been reached supporting a clear set of recommendations for intervention during the immediate and the mid-term post mass trauma phases. because it is unlikely that there will be evidence in the near or mid-term future from clinical trials that cover the diversity of disaster and mass violence circumstances, we assembled a worldwide panel of experts on the study and treatment of those exposed to disaster and mass violence to extrapolate from related fields of research, and to gain consensus on intervention principles. we identified five empirically supported intervention principles that should be used to guide and inform intervention and prevention efforts at the early to mid-term stages. these are promoting: 1) a sense of safety, 2) calming, 3) a sense of self- and community efficacy, 4) connectedness, and 5) hope.”
Husain, M. I., Umer, M., Chaudhry, I. B., Husain, M. O., Rahman, R., Shakoor, S., … Husain, N.. (2021). Relationship between childhood trauma, personality, social support and depression in women attending general medical clinics in a low and middle-income country. Journal of Affective Disorders
“Background: associations between childhood trauma, personality, and major depressive disorder (mdd) have been well established in studies conducted in high-income countries. however, there are limited studies on these associations in low and middle-income countries (lmics), where mdd is highly prevalent. we assessed the relationships between childhood trauma, personality, and mdd in women in karachi, pakistan. method: in this cross-sectional study of 455 female patients attending general medical outpatient clinics, a diagnosis of mdd was confirmed using the structured clinical interview for dsm-iv (scid); retrospective reports of childhood trauma were collected using the childhood trauma questionnaire (ctq); and big five personality traits were assessed using the neo personality inventory revised (neo pi-r). other measures included the life events questionnaire (leq) and the multidimensional scale of perceived social support (mspss). factors independently associated with mdd were determined using logistic regression analyses. results: of the 455 women recruited between august 1, 2011 and july 31, 2013, 242 (53%) had a diagnosis of mdd. women with mdd were significantly more likely to be separated, had more stressful life events and higher ctq scores. higher perceived social support, conscientiousness and extraversion were independently associated with significantly reduced odds of mdd. there were no significant associations between ctq scores and any of the neo pi-r subscales. limitations: ratings of childhood trauma were based on retrospective recall. conclusion: mdd and a history of childhood trauma were highly prevalent in pakistani women attending general medical clinics. interventions to prevent childhood trauma and promote social support in women may improve public mental health in lmics like pakistan.”
Fuchshuber, J., & Unterrainer, H. F.. (2020). Childhood Trauma, Personality, and Substance Use Disorder: The Development of a Neuropsychoanalytic Addiction Model. Frontiers in Psychiatry
“Background: while traditional psychoanalysis has been criticized as insufficient for the treatment of substance use disorder (sud), recent progress in the field of neuropsychoanalysis has generated new and promising hypotheses regarding its etiology. however, empirical research applying this framework has been sparse. aim and scope: the present overview aims at developing and empirically validating a neuroscientifically informed psychodynamic framework regarding the etiology of sud. for this purpose, this review provides a concise overview of the most relevant historical and contemporary psychoanalytic theories on sud etiology. furthermore, the original research summarized in this paper consists of three studies investigating connections between childhood trauma, primary emotions, personality structure and attachment, as well as their relation to sud development and treatment. conclusions: the results highlight the empirical validity of the neuropsychoanalytic approach towards sud etiology. in particular, the findings underscore the conceptualization of sud as a disorder related to dysfunctional attachment and affect regulation abilities especially linked to increased sadness and anger dispositions, which mediated the relationship between sud and traumatic childhood relationships. based on these findings, a refined model of sud etiology is proposed, which should be tested in future studies.”
Stevanović, A., Frančišković, T., & Vermetten, E.. (2016). Relationship of early-life trauma, war-related trauma, personality traits, and PTSD symptom severity: A retrospective study on female civilian victims of war. European Journal of Psychotraumatology
“Background: consequences of war-related traumatisation have mostly been investigated in military and predominant male populations, while research on female civilian victims of war has been neglected. furthermore, research of post-war posttraumatic stress disorder (ptsd) inwomen has rarely included early-life trauma in their prediction models, so the contribution of trauma in childhood and early youth is still unexplored. objective: to examine the relationship of early-life trauma, war-related trauma, personality traits, and symptoms of posttraumatic stress among female civilian victims of the recent war in croatia. method: the cross-sectional study included 394 participants, 293 war-traumatised adult women civilians, and 101 women without war-related trauma. participants were recruited using the snowball sampling method. the applied instruments included the clinician-administrated ptsd scale (caps), the neo personality inventory-revised (neo-pi-r), thewar stressors assessment questionnaire (wsaq), and the early trauma inventory self report-short form (etisr-sf). a hierarchical multiple regression analysis was performed to assess the prediction model of ptsd symptom severity measured by caps score for current ptsd. results: the prevalence of current ptsd (caps cut-off score65) in this cohort was 20.7%. the regression model that included age, early-life trauma, war-related trauma, neuroticism, and extraversion as statistically significant predictors explained 45.8% of variance in ptsd symptoms. conclusions: older age, exposure to early-life trauma, exposure to war-related traumatic events, high neuroticism, and low extraversion are independent factors associated with higher level of ptsd symptoms among women civilian victims of war.”
Yalch, M. M., Stewart, A. M., & Dehart, R. M.. (2021). Influence of Betrayal Trauma on Antisocial Personality Disorder Traits. Journal of Trauma and Dissociation
“Antisocial personality disorder (aspd) is linked to a number of social problems and accordingly is the focus of intensive empirical study. there is reason to believe that aspd is influenced at least in part by exposure to trauma, but there has been minimal research on the association between trauma and aspd traits. specifically, research has not examined how traumatic experiences with different degrees of interpersonal betrayal differentially influence aspd traits. this is notable in light of recent studies indicating that exposure to traumatic experiences high in betrayal (i.e., high betrayal trauma) is the primary predictor of borderline and narcissistic personality pathology. in this study, we examined the relative associations between high, medium, and low betrayal trauma and aspd traits in a sample recruited from amazon’s mechanical turk (n = 363) using structural equation modeling. results confirmed a strong association between trauma and aspd traits in general, although the influence of specific forms of trauma differed depending on both sex and how trauma was calculated (i.e., in terms of severity vs. exposure). in general, high betrayal trauma was the most consistent predictor of aspd traits for men, whereas medium and low betrayal traumas were more consistently associated with aspd traits for women. study findings extend research on betrayal trauma to more malevolent forms of personality pathology. sex differences in the influence of trauma across aspd traits suggest the possibility of sex-specific personality responses to trauma high in betrayal, a topic that can be addressed in the future research.”
Paris, J.. (1998). Does childhood trauma cause personality disorders in adults?. Canadian Journal of Psychiatry
“Objective: to examine the relationship between trauma in childhood and personality disorders in adulthood. method: a review of the literature was conducted. results: the reported associations between trauma and personality pathology are illuminated by the following research findings: 1) personality is heritable; 2) only a minority of patients with severe personality disorders report childhood trauma; and 3) children are generally resilient, and traumatic experiences do not consistently lead to psychopathology. conclusions: the role of trauma in the personality disorders is best understood in the context of gene-environment interactions.”
Bahari, A., Hasani, J., & Mashhadi Akbar Boojar, M.. (2021). Childhood trauma and type D personality: The endocrine and cardiovascular effects on stress reactivity. Journal of Health Psychology
“Both exaggerated and blunted cardiovascular stress reactions are associated with health problems. moreover, early life experiences and personality traits affect stress responses. regarding the childhood traumas and type d personality, this study aimed to compare the endocrine and cardiovascular reactions against acute laboratory stress. results showed that the simultaneous existence of childhood traumatic experiences and type d personality leads to exaggerated stress reactivity, while each factor results in a blunted cardiovascular response. although the cardiovascular responses are dampened in type d personality people, their endocrine reactions are exaggerated. the underlying mechanisms of blunted cardiovascular reactivity differ between childhood trauma and type d personality groups.”
Rutkowski, K., Dembińska, E., & Walczewska, J.. (2016). Effect of trauma onset on personality traits of politically persecuted victims. BMC Psychiatry
“Background: the hypothesis that traumatic experiences in early childhood impact personality formation and psychopathology is well known in psychology and psychiatry, but this is difficult to verify statistically in methodological terms. the aim of this study, conducted with politically persecuted poles, was to establish the influence of the time when trauma is experienced on the development of psychopathological symptoms. methods: the subjects were divided into two groups: those who had experienced trauma before age five (group 1) and those who experienced trauma at an older age (group 2). subjects in both groups suffered from chronic untreated post-traumatic stress disorder. in order to test the research hypothesis, the minnesota multiphasic personality inventory-2 profiles of both groups were compared using student’s t-test, and the mann-whitney u-test. results: statistically significant between-group differences were found for the f validity scale and the following clinical scales: hypochondriasis, depression, psychopathic deviate, psychasthenia, schizophrenia, and social introversion. all the significantly different scores were higher in the group traumatized in early childhood. people exposed to trauma under age five had profiles similar to those traumatized after age five, but they experienced their symptoms more intensely. conclusions: of clinical significance, higher scores on the psychasthenia, schizophrenia, and social introversion scales, especially on the psychopathic deviate scale, indicated pathology only in the early childhood trauma group. taken together, these symptoms lead to withdrawal and hindrance of social functioning. this outcome confirms the hypothesis of the influence of various early childhood factors (such as trauma) on personality formation and personality traits in adulthood.”
Sansone, R. A., & Sansone, L. A.. (2007). Childhood trauma, borderline personality, and eating disorders: A development cascade. Eating Disorders
“In this article, we discuss the nature and role of trauma in relationship to borderline personality disorder and eating disorders. as is clinically evident, trauma can result in a variety of psychological consequences. these consequences include both axis i and ii disorders. among the axis ii disorders, trauma appears to heighten the risk for the development of borderline, antisocial, avoidant, paranoid, and even schizotypal personality disorders. likewise, trauma may heighten the risk for developing an eating disorder. there appear to be complex inter-relationships among trauma, borderline personality disorder, and eating disorders. in this article, we attempt to summarize these inter-relationships.”
Green, K., & Browne, K.. (2020). Personality Disorder Traits, Trauma, and Risk in Perpetrators of Domestic Violence. International Journal of Offender Therapy and Comparative Criminology
“Crimes committed against partners and family members have devastating effects on victims. unfortunately, recidivism rates for offenders are high, and there is a need to establish risk factors that may be potential treatment targets. this study aimed to investigate childhood maltreatment, symptoms of trauma, and personality disorder (pd) traits in males convicted of domestic violence (dv) offences. data were extracted from the files of 40 males under the supervision of the probation service in the united kingdom. actual return to custody was recorded after a minimum follow-up of 6 months. self-reported childhood maltreatment was associated with increases in pd traits, posttraumatic symptoms, and assessed risk. however, maltreatment did not predict return to custody. tension-reducing behaviours and depressive symptoms predicted return to custody as did antisocial pd. these preliminary findings highlight important areas of future research, in particular, factors which may be relevant treatment targets in reducing the risk of recidivism.”
Li, Y., Lv, Q., Li, B., Luo, D., Sun, X., & Xu, J.. (2020). The role of trauma experiences, personality traits, and genotype in maintaining posttraumatic stress disorder symptoms among child survivors of the Wenchuan earthquake. BMC Psychiatry
“Background: posttraumatic stress disorder (ptsd) is the most prevalent type of psychiatric disorder among children after an earthquake. this study investigated the role of trauma experiences, personality traits, and genotype in the maintenance of ptsd symptoms. methods: in a previous large-scale epidemiological investigation 1 year after the wenchuan earthquake, 215 children with ptsd symptoms were selected at random with their blood samples collected. all of them were followed up, and their ptsd symptoms were assessed 3 years later. the adolescent version of the ucla ptsd reaction index, the earthquake exposure scale, and the junior eysenck personality questionnaire were used to determine ptsd symptoms, trauma experiences, and personality traits, respectively. we sequenced candidate genes involved in the regulation of long-term potentiation via nmda-type receptors to identify the related snp variations. results: being trapped for a longer period of time, feeling one’s own or a family member’s life to be in danger, losing a close family member or friend, extraversion, neuroticism, trkb, g72 and cntf were found to be associated with the maintenance of ptsd symptoms. conclusions: experiences, personality traits, and genotype influenced the maintenance of ptsd in child survivors who were considered to be followed up without medicine. this result could help to identify potential targets for treatment and promote the rational allocation of medical resources.”
Back, S. N., Flechsenhar, A., Bertsch, K., & Zettl, M.. (2021). Childhood Traumatic Experiences and Dimensional Models of Personality Disorder in DSM-5 and ICD-11: Opportunities and Challenges. Current Psychiatry Reports
“Purpose of review: childhood trauma is an important risk factor for the development of personality disorders (pds), yet most research has been devoted to categorical models of personality pathology. considering the introduction of a dimensional pd model with icd-11, we review current findings related to various forms of childhood trauma, and pds, operationalized in the form of personality functioning and maladaptive traits. we focus on the magnitude of associations and examine specific relationships between emotional and physical trauma with areas of personality functioning and single traits. recent findings: two studies showed a strong association between childhood trauma and personality dysfunction. seven studies, including clinical and forensic samples, demonstrated heterogeneous associations between various forms of childhood trauma and maladaptive traits. overall, four studies indicated a slightly stronger association between personality dysfunction, maladaptive trait expression, and higher levels of emotional trauma than for physical or sexual trauma. regarding specific trait domains and childhood trauma, most studies yielded the strongest associations for either psychoticism or detachment. summary: research on childhood trauma and dimensional pd models (i.e., personality functioning and traits) has the potential to contribute to a better understanding of their complex relationship. however, high intercorrelations among different types of childhood trauma, areas of personality functioning, and trait domains increase the difficulty of disentangling single effects. more research is needed including clinical and non-western samples, especially considering the upcoming icd-11 classification.”
Sheehan, A. E., Bounoua, N., Miglin, R., Spielberg, J. M., & Sadeh, N.. (2021). A multilevel examination of lifetime aggression: Integrating cortical thickness, personality pathology and trauma exposure. Social Cognitive and Affective Neuroscience
“Aggression represents a significant public health concern, causing serious physical and psychological harm. although many studies have sought to characterize the etiology of aggression, research on the contributions of risk factors that span multiple levels of analysis for explaining aggressive behavior is lacking. to address this gap, we investigated the direct and unique contributions of cortical thickness (level 1), pathological personality traits (level 2) and trauma exposure (level 3) for explaining lifetime physical aggression in a high-risk sample of community adults (n = 129, 47.3% men). first, the frequency of lifetime aggression was inversely associated with cortical thickness in regions of prefrontal and temporal cortices that have been implicated in executive functioning, inhibitory mechanisms and socio-emotional processing. further, aggression was positively associated with pathological personality traits (antagonism and disinhibition) and exposure to assaultive trauma. notably, all three levels of analysis (cortical thickness, pathological personality traits and assaultive trauma exposure) explained non-overlapping variance in aggressive behavior when examined simultaneously in integrative models. together, the findings provide a multilevel assessment of the biopsychosocial factors associated with the frequency of aggression. they also indicate that cortical thickness explains novel variance in these harmful behaviors not captured by well-established personality and environmental risk factors for aggression.”
Watkeys, O. J., Kremerskothen, K., Quidé, Y., Fullerton, J. M., & Green, M. J.. (2018). Glucocorticoid receptor gene (NR3C1) DNA methylation in association with trauma, psychopathology, transcript expression, or genotypic variation: A systematic review. Neuroscience and Biobehavioral Reviews
“The glucocorticoid receptor gene (nr3c1) is a critical component of the stress response system. cytosine methylation of nr3c1 has been repeatedly associated with trauma and mental disorders, including major depression, post-traumatic stress disorder, anxiety, and personality disorders, suggesting that nr3c1 methylation may play a role in stress-related psychopathology. we systematically reviewed 55 studies examining nr3c1 dna methylation in association with trauma exposure, psychopathology, gene expression, and/or common genetic variants. overall, a number of nr3c1 cpg sites were significantly associated with trauma or psychopathology, but significant findings were often inconsistent across studies. this lack of consistency is likely influenced by significant methodological variability – experimentally and analytically – across studies. selected common genetic variants show no significant effect on nr3c1 cpg methylation. in contrast, there was ample evidence linking increased methylation of nr3c1 to reduced expression of this gene. the inverse association between methylation and gene expression shown across eight out of ten studies supports the notion that methylation in the promoter region of nr3c1 is associated with transcriptional silencing.”
Light, A. E., Holt-Lunstad, J., Porter, C. L., & Light, K. C.. (2019). Early life trauma: An exploratory study of effects on OXTR and NR3C1 gene expression and nurturing self-efficacy in mothers of infants. International Journal of Psychophysiology
“Background: in animals, adverse early experience alters oxytocinergic and glucocorticoid activity and maternal behavior in adulthood. this preliminary study explored associations among childhood trauma (loss of a parent or sexual abuse in childhood), maternal self-efficacy, and leukocyte gene expression (mrna) of oxytocin and glucocorticoid receptors (oxtr and nr3c1) in mothers of infants. methods: 62 mothers (20 with early life trauma) with healthy 3-month old infants reported maternal self-efficacy, depression, infant temperament, and overall social support; the effects of early trauma on these measures were assessed. of these, 35 mothers (14 with early trauma) underwent blood draws after 2 infant feeding times; their oxtr and nr3c1 mrna was compared to a control group of 25 no-infant women without early trauma, and also was examined for associations with self-efficacy. results: oxtr mrna was increased in mothers of infants versus no-infant controls (p < 0.0003), and mothers with greatest prior maternal experience had higher oxtr than those with less experience (0–2 vs. 3+ older children, p < 0.033). mothers with early trauma and less maternal experience had lower oxtr mrna than no-trauma mothers (p < 0.029) and lower nr3c1 mrna than controls (p < 0.004). mothers with depression also had lower nr3c1 than other mothers (p < 0.003) but did not differ in oxtr. mothers with early trauma also reported their support network to be less helpful and more upsetting and unpredictable than other mothers (p < 0.035–p < 0.005). regarding maternal behavior, in mothers with early trauma, helpful support networks increased self-reported nurturing self-efficacy when babies were not fussy but decreased it with fussy babies (p < 0.05). support was unrelated to self-efficacy in no-trauma mothers. similarly, among mothers with low oxtr or nr3c1 (−1sd, most having early trauma and lower maternal experience), greater support was associated with lower self-efficacy (p < 0.05), while mothers with high oxtr or nr3c1 (+1sd) tended to have higher self-efficacy with greater support. conclusions: these preliminary findings need confirmation in a larger sample but suggest that childhood trauma influences maternal behavior and both oxtr and nr3c1 pathways in mothers of infants, and that both depression and prior maternal experience may be other important factors. effects on maternal behavior appear to require more complex modeling.”
de Assis Pinheiro, J., Freitas, F. V., Borçoi, A. R., Mendes, S. O., Conti, C. L., Arpini, J. K., … Alvares-da-Silva, A. M.. (2021). Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation. Scientific Reports
“The nr3c1 glucocorticoid receptor (gr) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. nr3c1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. previous studies have reported that stressful events are involved in nr3c1 gene methylation, suggesting that its regulation under environmental effects is complex. the present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to nr3c1 methylation in adults. this study included 386 individual users of the brazilian public unified health system (sus), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. data were correlated with nr3c1 methylation, determined using dna pyrosequencing. the results showed that alcohol consumption, overweight, and high cortisol levels were related to nr3c1 demethylation, while depression was related to its methylation. habits, lifestyle, and health status may influence nr3c1 gene regulation via methylation, revealing the complexity of environmental impacts on nr3c1 methylation.”
Çetin, Ş., Sözeri-Varma, G., Çetin, G. O., Türel, S., Uğurlu, T. T., & Özdel, O.. (2022). The Relationship Between Methylation of the Glucocorticoid Receptor Gene (NR3C1) and Childhood Trauma and Alexithymia. Israel Journal of Psychiatry
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“Background: childhood traumas affect the hypothalamo-pituitary-adrenal (hpa) axis functions, and therefore emotional regulation response to stress. glucocorticoid receptor (gr) gene nr3c1 plays a key role in hpa axis. the aim of the study was to investigate the relationship between methylation of nr3c1 gene with childhood trauma and alexithymia in somatic symptom disorder (ssd) and major depressive disorder (mdd). methods: a total of 48 patients with ssd, 50 patients with mdd and 50 healthy controls were included in the study. mongomery-asberg depression rating scale (madrs), toronto alexithymia scale (tas-20), and the childhood trauma questionnaire (ctq) were applied to the participants. methylation levels of the nr3c1 gene were determined quantitatively in dna blood samples. results: tas-20 and ctq total scores were found to be the highest in patients with ssd. ctq scores were observed to be higher in ssd and mdd compared with the control group. nr3c1 gene methylation levels were found to be lowest in ssd and highest in mdd. there was no correlation between scores of tas-20 and nr3c1 methylation. high alexithymia level was predictive for ssd (or: 1.237, 95% ci: 1.018-1.504). high methylation levels increase the risk of mdd (or: 7.449, 95% ci: 3.702-14.986), decrease the risk of ssd (or: 0.00006 95% ci: 0.000-0.038). conclusion: our results show that emotion processing processes and gr methylation are different in both disorders. childhood trauma may be related to epigenetic changes in the gr gene. the type of epigenetic changes may result in vulnerability to different psychiatric disorders.”
Alexander, N., Kirschbaum, C., Wankerl, M., Stauch, B. J., Stalder, T., Steudte-Schmiedgen, S., … Miller, R.. (2018). Glucocorticoid receptor gene methylation moderates the association of childhood trauma and cortisol stress reactivity. Psychoneuroendocrinology
“Exposure to childhood trauma (ct) has been linked to sustained dysregulations of major stress response systems, including findings of both exaggerated and attenuated hypothalamus–pituitary–adrenal (hpa) axis activity. likewise, ct constitutes a common risk factor for a broad range of psychiatric conditions that involve distinct neuroendocrine profiles. in this study, we investigated the role of epigenetic variability in a stress-related gene as a potential mediator or moderator of such differential trajectories in ct survivors. for this, we screened adult volunteers for ct and recruited a healthy sample of 98 exposed (67 with mild-moderate, 31 with moderate-severe exposure) and 102 control individuals, with an equal number of males and females in each group. dna methylation (dnam) levels of the glucocorticoid receptor exon 1f promoter (nr3c1-1f) at functionally relevant sites were analyzed via bisulfite pyrosequencing from whole blood samples. participants were exposed to a laboratory stressor (trier social stress test) to assess salivary cortisol stress responses. the major finding of this study indicates that dnam in a biologically relevant region of nr3c1-1f moderates the specific direction of hpa-axis dysregulation (hypo- vs. hyperreactivity) in adults exposed to moderate-severe ct. those trauma survivors with increased nr3c1-1f dnam displayed, on average, 10.4 nmol/l (62.3%) higher peak cortisol levels in response to the tsst compared to those with low dnam. in contrast, unexposed and mildly-moderately exposed individuals displayed moderately sized cortisol stress responses irrespective of nr3c1-1f dnam. contrary to some prior work, however, our data provides no evidence for a direct association of ct and nr3c1-1f dnam status. according to this study, epigenetic changes of nr3c1-1f may provide a more in-depth understanding of the highly variable neuroendocrine and pathological sequelae of ct.”
Vangeel, E. B., Kempke, S., Bakusic, J., Godderis, L., Luyten, P., Van Heddegem, L., … Claes, S.. (2018). Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients. Journal of Psychosomatic Research
“Objective although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (cfs) is associated with hypothalamic-pituitary-adrenal (hpa) axis dysregulation and trauma in early childhood. consistent with findings suggesting that early life stress-induced dna methylation changes may underlie dysregulation of the hpa axis, we previously found evidence for the involvement of glucocorticoid receptor (gr) gene (nr3c1) methylation in whole blood of cfs patients. methods in the current study, we assessed nr3c1-1f region dna methylation status in peripheral blood from a new and independent sample of 80 female cfs patients and 91 female controls. in cfs patients, history of childhood trauma subtypes was evaluated using the childhood trauma questionnaire short form (ctq-sf). results although absolute methylation differences were small, the present study confirms our previous findings of nr3c1-1f dna hypomethylation at several cpg sites in cfs patients as compared to controls. following multiple testing correction, only cpg_8 remained significant (dna methylation difference: 1.3% versus 1.5%, p < 0.001). in addition, we found associations between dna methylation and severity of fatigue as well as with childhood emotional abuse in cfs patients, although these findings were not significant after correction for multiple testing. conclusions in conclusion, we replicated findings of nr3c1-1f dna hypomethylation in cfs patients versus controls. our results support the hypothesis of hpa axis dysregulation and enhanced gr sensitivity in cfs.”
Martín-Blanco, A., Ferrer, M., Soler, J., Salazar, J., Vega, D., Andión, O., … Pascual, J. C.. (2014). Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder. Journal of Psychiatric Research
Perroud, N., Dayer, A., Piguet, C., Nallet, A., Favre, S., Malafosse, A., & Aubry, J. M.. (2014). Childhood maltreatment and methylation of the glucocorticoid receptor gene NR3C1 in bipolar disorder. British Journal of Psychiatry
“Background early-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. this may be the consequence of a sustained alteration of the hypothalamic-pituitary-adrenal (hpa) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (nr3c1). aims to investigate whether severity of childhood maltreatment isassociated with increased methylation of the exon 1f nr3c1 promoter in bipolar disorder. method a sample of people with bipolar disorder (n = 99) were assessed for childhood traumatic experiences. the percentage of nr3c1 methylation was measured for each participant.results the higher the number of trauma events, the higher was the percentage of nr3c1 methylation (β = 0.52, 95% ci 0.46-0.59, p”0.0001). the severity of each type of maltreatment (sexual, physical and emotional) was also associated with nr3c1 methylation status. conclusionsearly-life adversities have a sustained effect on the hpa axis through epigenetic processes and this effect may be measured in peripheral blood. this enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder. declaration of interest none.”
Straight, B., Fisher, G., Needham, B. L., Naugle, A., Olungah, C., Wanitjirattikal, P., … Lalancette, C.. (2021). Lifetime stress and war exposure timing may predict methylation changes at NR3C1 based on a pilot study in a warrior cohort in a small-scale society in Kenya. American Journal of Human Biology
“Objectives: candidate gene methylation studies of nr3c1 have identified associations with psychosocial adversity, including war trauma. this pilot study (sample sizes from 22 to 45 for primary analyses) examined nr3c1 methylation in a group of kenyan pastoralist young men in relation to culturally relevant traumatic experiences, including participation in coalitional lethal gun violence. methods: adolescent and young adult samburu men (‘warriors’) were recruited for participation. dna was obtained from whole saliva and methylation analyses performed using mass spectrometry. we performed a data reduction of variables from a standardized instrument of lifetime stress using a factor analysis and we assessed the association between the extracted factors with culturally relevant and cross-culturally comparative experiences. results: cumulative lifetime trauma exposure and forms of violence to which warriors are particularly susceptible were associated with dna methylation changes in the nr3c1 1f promoter region but not in the nr3c1 1d promoter region. however, sensitivity analyses revealed significant associations between individual cpg sites in both regions and cumulative stress exposures, war exposure timing, and war fatalities. conclusions: this study supports the importance of nr3c1 methylation changes in response to challenging life circumstances, including in a global south cultural context that contrasts in notable ways from global north contexts and from the starkly tragic examples of the rwandan genocide and war-associated rape explored in recent studies. timing of traumatic exposure and culturally salient means to measure enduring symptoms of trauma remain important considerations for dna methylation studies.”
Malhi, G. S., Das, P., Outhred, T., Dobson-Stone, C., Irwin, L., Gessler, D., … Mannie, Z.. (2019). Effect of stress gene-by-environment interactions on hippocampal volumes and cortisol secretion in adolescent girls. Australian and New Zealand Journal of Psychiatry
“Objective: adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. genes interacting with the environment (g × e) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. in this study, we assessed the effects of stress system g × e interactions on hippocampal volumes and cortisol secretion in adolescent girls. methods: we recruited 229 girls aged 12–18 years, and scans were obtained from 202 girls. of these, 76 had been exposed to higher emotional trauma (abuse or neglect). hippocampal volumes were measured using freesurfer and high-resolution structural magnetic resonance imaging scans. saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: fkbp5, nr3c1 (both n = 194) and nr3c2 (n = 193). results: among girls with the ‘g’ allelic variant of the nr3c1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes (n = 44; mean = 4069.58 mm 3 , standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant (n = 69; mean = 4222.34 mm 3 , standard deviation = 366.74). conclusion: in healthy adolescents, interactions between emotional trauma and the ‘protective’ nr3c1 ‘gg’ variant seem to induce reductions in left hippocampal volumes. these g × e interactions suggest that vulnerability to mood disorders is perhaps driven by reduced ‘protection’ that may be specific to emotional trauma. this novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.”
Smart, C., Strathdee, G., Watson, S., Murgatroyd, C., & McAllister-Williams, R. H.. (2015). Early life trauma, depression and the glucocorticoid receptor gene-an epigenetic perspective. Psychological Medicine
“Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. family history remains the ‘gold standard’ for both risk stratification and prognosis in complex phenotypes such as depression. meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. a heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic-pituitary-adrenal (hpa) axis. the glucocorticoid receptor (gr) gene (nr3c1) has been found to be susceptible to epigenetic modification, specifically dna methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life. method. in this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the hpa axis and the nr3c1 gene. difficulties with the design of these studies are also explored. results. future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. the complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges. conclusions. the work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential dna methylation patterns in nr3c1 as well as novel therapeutic targets.”
Qi, R., Luo, Y., Zhang, L., Weng, Y., Surento, W., Xu, Q., … Thompson, P. M.. (2021). Decreased functional connectivity of hippocampal subregions and methylation of the NR3C1 gene in Han Chinese adults who lost their only child. Psychological Medicine
“Background losing one’s only child is a major traumatic life event that may lead to post-traumatic stress disorder (ptsd); however, the underlying mechanisms of its psychological consequences remain poorly understood. here, we investigated subregional hippocampal functional connectivity (fc) networks based on resting-state functional magnetic resonance imaging and the deoxyribonucleic acid methylation of the human glucocorticoid receptor gene (nr3c1) in adults who had lost their only child. methods a total of 144 han chinese adults who had lost their only child (51 adults with ptsd and 93 non-ptsd adults [trauma-exposed controls]) and 50 controls without trauma exposure were included in this fmri study (age: 40-67 years). fcs between hippocampal subdivisions (four regions in each hemisphere: cornu ammonis1 [ca1], ca2, ca3, and dentate gyrus [dg]) and methylation levels of the nr3c1 gene were compared among the three groups. results trauma-exposed adults, regardless of ptsd diagnosis, had weaker positive fc between the left hippocampal ca1, left dg, and the posterior cingulate cortex, and weaker negative fc between the right ca1, right dg, and several frontal gyri, relative to healthy controls. compared to non-ptsd adults, ptsd adults showed decreased negative fc between the right ca1 region and the right middle/inferior frontal gyri (mfg/ifg), and decreased negative fc between the right dg and the right superior frontal gyrus and left mfg. both trauma-exposed groups showed lower methylation levels of the nr3c1 gene. conclusions adults who had lost their only child may experience disrupted hippocampal network connectivity and nr3c1 methylation status, regardless of whether they have developed ptsd.”
Schür, R. R., van Leeuwen, J. M. C., Houtepen, L. C., Joëls, M., Kahn, R. S., Boks, M. P., & Vinkers, C. H.. (2018). Glucocorticoid receptor exon 1 F methylation and the cortisol stress response in health and disease. Psychoneuroendocrinology
“Childhood trauma has been proposed to increase vulnerability to develop psychopathology in part through an altered cortisol stress response. research in rats has suggested that this effect is mediated by methylation in the glucocorticoid receptor 1 7 region (gr-1 7 or gr-1 f in humans), with higher methylation after poor maternal care leading to an increased cortisol stress response in adulthood. in humans, the associations between childhood trauma and gr-1 f methylation or the cortisol stress response are equivocal. remarkably, evidence for the relation between gr-1 f methylation and the cortisol stress response has been conflicting as well. to further explore this, we investigated the associations of peripheral gr-1 f methylation (52 cpgs) with the cortisol stress response (trier social stress test) and with childhood trauma in three independent studies (total n = 241) including healthy controls, patients with schizophrenia and bipolar disorder and unaffected siblings of patients with one of these disorders. we did not find any significant association between gr-1 f methylation and the cortisol stress response (areas under the curve) or childhood trauma, nor did we observe any group differences between patients, siblings and healthy controls. our findings do not support gr-1 f methylation as a proxy for the cortisol stress response, nor its link with childhood trauma or psychopathology. these results suggest that multifactorial models for stress-related psychopathology are needed. alternatively, future longitudinal studies may reveal gr-1 f methylation to be a useful parameter at an individual level.”
Yehuda, R., Flory, J. D., Bierer, L. M., Henn-Haase, C., Lehrner, A., Desarnaud, F., … Meaney, M. J.. (2015). Lower Methylation of Glucocorticoid Receptor Gene Promoter 1F in Peripheral Blood of Veterans with Posttraumatic Stress Disorder. Biological Psychiatry
“BACKGROUND: enhanced glucocorticoid receptor (gr) sensitivity is present in people with posttraumatic stress disorder (ptsd), but the molecular mechanisms of gr sensitivity are not understood. epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained ptsd symptoms given that ptsd develops in only a subset of trauma survivors. methods: cytosine methylation of a relevant promoter of the gr gene (nr3c1-1f promoter) and three functional neuroendocrine markers of hypothalamic-pituitary-adrenal axis function were examined in a sample of 122 combat veterans. results: lower nr3c1-1f promoter methylation in peripheral blood mononuclear cells (pbmcs) was observed in combat veterans with ptsd compared with combat-exposed veterans who did not develop ptsd. nr3c1-1f promoter methylation was also associated with three functional measures of glucocorticoid activity that have been associated with ptsd in combat veterans: pbmcs’ lysozyme inhibition on the lysozyme suppression test, plasma cortisol decline on the low-dose (.50 mg) dexamethasone suppression test, and 24-hour urinary cortisol excretion. finally, nr3c1-1f promoter methylation was inversely correlated with clinical markers and symptoms associated with ptsd. conclusions: alterations in nr3c1-1f promoter methylation may reflect enduring changes resulting from combat exposure that lead to functional neuroendocrine alterations. because epigenetic measures are thought to reflect enduring effects of environmental exposures, they may be useful in distinguishing combat-exposed veterans who do or do not develop ptsd.”
Vangeel, E., Van Den Eede, F., Hompes, T., Izzi, B., Del Favero, J., Moorkens, G., … Claes, S.. (2015). Chronic fatigue syndrome and DNA hypomethylation of the glucocorticoid receptor gene promoter 1F Region: Associations with HPA Axis Hypofunction and childhood trauma. Psychosomatic Medicine
“Objectives: chronic fatigue syndrome (cfs) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (gr) sensitivity. in addition, childhood trauma is considered a major risk factor for the syndrome. this study examinesdna methylation of the gr gene (nr3c1) in cfs and associations with childhood sexual and physical trauma. methods: quantification of dna methylation within the 1f promoter region of nr3c1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using sequenom epityper. further, we examined the association of nr3c1-1f promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. mann-whitney u tests and spearman correlations were used for statistical analyses. results: overall nr3c1-1f dna methylation was lower in patients with cfs than in controls. after cytosine guanine dinucleotide (cpg)-specific analysis, cpg-1.5 remained significant after bonferroni correction (adjusted p = .0014).within the cfs group, overall methylation (p = 0.477, p = .016) and selective cpg units (cpg-1.5: p = 0.538, p = .007; cpg-12.13: p = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. there was no significant difference in nr3c1-1f methylation between traumatized and nontraumatized patients. conclusions:we found evidence of nr3c1 promoter hypomethylation in female patients with cfs and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (gr hypersuppression). however, we found no evidence of an additional effect of childhood trauma on cfs via alterations in nr3c1 methylation.”
Fiacco, S., Gardini, E. S., Mernone, L., Schick, L., & Ehlert, U.. (2019). DNA Methylation in Healthy Older Adults With a History of Childhood Adversity—Findings From the Women 40+ Healthy Aging Study. Frontiers in Psychiatry
“Background: adversity in early development seems to increase the risk of stress-related somatic disorders later in life. physiologically, functioning of the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes is often discussed as long-term mediators of risk. in particular, dna methylation in the glucocorticoid receptor gene promoter (nr3c1) has been associated with type and strength of early life adversity and subsequent effects on hpa axis signaling in humans. animal studies, moreover, suggest changes in dna methylation in the estrogen receptor gene (erα) upon early life adversity. we investigated the association of type and severity of childhood adversity with methylation in nr3c1 and erα and additionally considered associations between methylation and steroid hormone secretion. methods: the percentage of methylation within the nr3c1 promoter and the erα shore was investigated using dried blood spot samples of 103 healthy women aged 40–73 years. childhood adversity was examined with the childhood trauma questionnaire. linear regression analyses were performed with methylation as dependent variable and the experience of emotional abuse and neglect, physical abuse and neglect, and sexual abuse (compared to non-experience) as independent variables. all analyses were controlled for age, bmi, annual household income, and smoking status and were adjusted for multiple testing. results: overall, over 70% of the sample reported having experienced any kind of abuse or neglect of at least low intensity. there were no significant associations between childhood adversity and methylation in the nr3c1 promoter (all p >.10). participants reporting emotional abuse showed significantly higher methylation in the erα shore than those who did not (p =.001). additionally, higher levels of adversity were associated with higher levels of erα shore methylation (p =.001). conclusion: in healthy women, early life adversity does not seem to result in nr3c1 promoter hypermethylation in midlife and older age. this is the first study in humans to suggest that childhood adversity might, however, epigenetically modify the erα shore. further studies are needed to gain a better understanding of why some individuals remain healthy and others develop psychopathologies in the face of childhood adversity.”
Perroud, N., Paoloni-Giacobino, A., Prada, P., Olié, E., Salzmann, A., Nicastro, R., … Malafosse, A.. (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: A link with the severity and type of trauma. Translational Psychiatry
Womersley, J. S., Martin, L. I., van der Merwe, L., Seedat, S., & Hemmings, S. M. J.. (2018). Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents. Metabolic Brain Disease
“Anxiety sensitivity (as) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. we examined whether genetic variation in three stress response genes, crhr1, nr3c1, and fkbp5, interact with childhood trauma (ct) to predict as in south african adolescents. xhosa (n = 634) and coloured (n = 317) students completed self-report measures of as and ct, and a total of eighteen polymorphisms within crhr1, nr3c1, and fkbp5 were genotyped. differences in as based on genetic variation and ct were analysed within population and gender groups using multiple linear regression. associations were found between as and fkbp5 rs9296158 (p = 0.025) and rs737054 (p = 0.045) in coloured males. analysis of gene x ct interactions indicated that nr3c1 rs190488 cc-genotype, nr3c1 rs10482605 g-allele addition, and fkbp5 rs3800373 c-allele addition protect against as with increasing ct in xhosa females (p = 0.009), xhosa males (p = 0.036) and coloured males (p = 0.049), respectively. we identified two different protective single nucleotide polymorphism (snp) combinations in a four-snp crhr1 haplotype in coloured males. an analysis of the interaction between ct and a six-snp fkbp5 haplotype in coloured males revealed both protective and risk allelic combinations. our results provide evidence for the influence of both genetic variation in crhr1, nr3c1 and fkbp5, as well as ct x snp interactions, on as in south african adolescents. this study reinforces the importance of examining the influence of gene-environment (g x e) interactions within gender and population groups.”
Rovaris, D. L., Mota, N. R., Bertuzzi, G. P., Aroche, A. P., Callegari-Jacques, S. M., Guimarães, L. S. P., … Grassi-Oliveira, R.. (2015). Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment. Journal of Psychiatric Research
“The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (nr3c2 and nr3c1, respectively). one hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. childhood adversities were assessed using the childhood trauma questionnaire (ctq), and withdrawal symptoms were assessed using the cocaine selective severity assessment (cssa) scale. conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. we found an interaction between the rs5522-val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (odds ratio=4.0, p=0.001). moreover, a nr3c2-nr3c1 interaction (p = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. in the post hoc analysis, concomitant carriers of the nr3c2 rs5522-val and nr3c1 rs6198-g alleles showed lower overall severity scores when compared to other genotype groups (p-values ≤ 0.035). this gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (hpa) axis dysregulation in cocaine addiction. additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between nr3c2 and nr3c1 genes.”
Holmes, L., Shutman, E., Chinaka, C., Deepika, K., Pelaez, L., & Dabney, K. W.. (2019). Aberrant epigenomic modulation of glucocorticoid receptor gene (NR3C1) in early life stress and major depressive disorder correlation: Systematic review and quantitative evidence synthesis. International Journal of Environmental Research and Public Health
“Early life stress (els) induced by psychological trauma, child maltreatment, maternal separation, and domestic violence predisposes to psycho-behavioral pathologies during adulthood, namely major depressive disorder (mdd), anxiety, and bipolar affective disorder. while environmental data are available in illustrating this association, data remain to be established on the epigenomic underpinning of the nexus between els and mdd predisposition. specifically, despite the observed aberrant epigenomic modulation of the nr3c1, a glucocorticoid receptor gene, in early social adversity and social threats in animal and human models, reliable scientific data for intervention mapping in reducing social adversity and improving human health is required. we sought to synthesize the findings of studies evaluating (a) epigenomic modulations, mainly dna methylation resulting in mdd following els, (b) epigenomic modifications associated with els, and (c) epigenomic alterations associated with mdd. a systematic review and quantitative evidence synthesis (qes) were utilized with the random effect meta-analytic procedure. the search strategy involved both the pubmed and hand search of relevant references. of the 1534 studies identified through electronic search, 592 studies were screened, 11 met the eligibility criteria for inclusion in the qes, and 5 examined els and mdd; 4 studies assessed epigenomic modulation and els, while 2 studies examined epigenomic modulations and mdd. the dense dna methylation of the 1f exon of the nr3c1, implying the hypermethylated region of the glucocorticoid receptor gene, was observed in the nexus between els and mdd, common effect size (ces) = 14.96, 95%ci, 10.06–19.85. with respect to epigenomic modulation associated with child els, hypermethylation was observed, ces = 23.2%, 95%ci, 8.00–38.48. in addition, marginal epigenomic alteration was indicated in mdd, where hypermethylation was associated with increased risk of mdd, ces = 2.12%, 95%ci, −0.63–4.86. substantial evidence supports the implication of nr3c1 and environmental interaction, mainly dna methylation, in the predisposition to mdd following els. this qes further supports aberrant epigenomic modulation identified in els as well as major depressive episodes involving dysfunctional glucocorticoid-mediated negative feedback as a result of allostatic overload. these findings recommend prospective investigation of social adversity and its predisposition to the mdd epidemic via aberrant…”
Grillault Laroche, D., Curis, E., Bellivier, F., Nepost, C., Courtin, C., Etain, B., & Marie-Claire, C.. (2020). Childhood maltreatment and HPA axis gene expression in bipolar disorders: A gene network analysis. Psychoneuroendocrinology
“Introduction: bipolar disorder (bd) is highly associated with childhood maltreatment (cm), the exposure to such early adversity being suggested to disrupt the expression of several biological pathways. this study aims at exploring associations between the mrna levels of 9 hpa axis genes in lymphoblastoid cell lines from patients with bd according to their self-reported exposure to cm. methods: the sample consisted of 33 caucasian patients with a diagnosis of bd type 1, assessed for the exposure to cm with the childhood trauma questionnaire (ctq). quantitative rt-pcr was performed on 9 transcripts of the hpa axis genes: dgkh, fkbp5, nr3c1, sgk1, sgk2, sgk3, ska2, stat5a and ucn. rt-qpcr data were analyzed using the method of disjoint gene networks with sarp.compo package for r. results: we found no associations between ctq total score and the amount of hpa axis transcripts neither in univariate analyses, nor with network analyses. emotional abuse (ea) was associated with a significant decreased expression of two transcripts, dgkh (p = 0.009) and nr3c1 (p = 0.04). this was confirmed by the disjoint network analysis, which showed that nr3c1 and dgkh were expressed differently from the rest of the hpa axis network in presence of emotional abuse. discussion: this study described the expression levels of a comprehensive set of hpa axis genes according to childhood maltreatment in a sample of patients with bd type 1 and suggested that emotional abuse decreased the expression of nr3c1 and dgkh. our results require further replication in independent larger samples.”
Sheerin, C. M., Lind, M. J., Bountress, K. E., Marraccini, M. E., Amstadter, A. B., Bacanu, S. A., & Nugent, N. R.. (2020). Meta-Analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder. Journal of Traumatic Stress
“The hypothalamic-pituitary-adrenal (hpa) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (ptsd). although numerous hpa-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. to address these inconsistencies in the ptsd candidate gene literature, we conducted meta-analyses of hpa-related genes from both a traditional single nucleotide polymorphism (snp)–level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. database searches (pubmed and psycinfo) identified 24 unique articles examining six hpa-axis genes in ptsd; analyses were conducted on four genes (adcyap1r1, crhr1, fkbp5, nr3c1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, ptsd as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. findings from snp-level analyses indicated that two variants (rs9296158 in fkbp5 and rs258747 in nr3c1) were nominally associated with ptsd, ps =.001 and.001, respectively, following multiple testing correction. at the gene level, significant relations between ptsd and both nr3c1 and fkbp5 were detected and robust to sensitivity analyses. although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for fkbp5 and nr3c1 in risk for ptsd. overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of ptsd.”
Peng, H., Zhu, Y., Strachan, E., Fowler, E., Bacus, T., Roy-Byrne, P., … Zhao, J.. (2018). Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings from Two Monozygotic Twin Studies. Psychosomatic Medicine
“Objective dna methylation has been associated with both early life stress and depression. this study examined the combined association of dna methylation at multiple cpg probes in five stress-related genes with depressive symptoms and tested whether these genes methylation mediated the association between childhood trauma and depression in two monozygotic (mz) twin studies. methods the current analysis comprised 119 mz twin pairs (84 male pairs [mean = 55 years] and 35 female pairs [mean = 36 years]). peripheral blood dna methylation of five stress-related genes (bdnf, nr3c1, slc6a4, maoa, and maob) was quantified by bisulfite pyrosequencing or 450k beadchip. we applied generalized poisson linear-mixed models to examine the association between each single cpg methylation and depressive symptoms. the joint associations of multiple cpgs in a single gene or all five stress-related genes as a pathway were tested by weighted truncated product method. mediation analysis was conducted to test the potential mediating effect of stress gene methylation on the relationship between childhood trauma and depressive symptoms. results multiple cpg probes showed nominal individual associations, but very few survived multiple testing. gene-based or gene-set approach, however, revealed significant joint associations of dna methylation in all five stress-related genes with depressive symptoms in both studies. moreover, two cpg probes in the bdnf and nr3c1 mediated approximately 20% of the association between childhood trauma and depressive symptoms. conclusions dna methylation at multiple cpg sites are jointly associated with depressive symptoms and partly mediates the association between childhood trauma and depression. our results highlight the importance of testing the combined effects of multiple cpg loci on complex traits and may unravel a molecular mechanism through which adverse early life experiences are biologically embedded.”
Nöthling, J., Malan-Müller, S., Abrahams, N., Hemmings, S. M. J., & Seedat, S.. (2020). Epigenetic alterations associated with childhood trauma and adult mental health outcomes: A systematic review. World Journal of Biological Psychiatry
“Objectives: multiple, chronic and repeated trauma exposure in childhood is associated with adverse mental health outcomes in adulthood. in this paper we synthesise the literature on epigenetic modifications in childhood trauma (ct) and the mediating effects of differential epigenetic mechanisms on the association between ct and the later onset of psychiatric disorders. methods: we reviewed the literature up to march 2018 in four databases: pubmed, web of science, ebscohost and scopus. non-human studies were excluded. all studies investigating ct exposure both in healthy adults (18years and older) and adults with psychiatric disorders were included. results: thirty-six publications were included. for mood disorders, methylation of the glucocorticoid receptor nr3c1 gene, specifically at the ngfi-a binding site in exon 1f, and correlation with ct was a robust finding. several studies documented differential methylation of slc6a4, bdnf, oxtr and fkbp5 in association with ct. common pathways identified include neuronal functioning and maintenance, immune and inflammatory processes, chromatin and histone modification, and transcription factor binding. conclusions: a variety of epigenetic mediators that lie on a common pathway between ct and psychiatric disorders have been identified, although longitudinal studies and consistency in methodological approach are needed to disentangle cause and effect associations.”
Brown, V.. (2021). Methylation of the glucocorticoid receptor gene NR3C1: a summary for clinicians working with children and families. BJPsych Open
“Aims it has been shown that the glucocorticoid receptor nr3c1 gene can be methylated (‘switched off’) in response to early adversity. methylation has also been linked to physiological changes in the body’s response to stress by changing the sensitivity of the hypothalamic-pituitary-adrenal (hpa) axis. in adults, associations have been made between nr3c1 methylation and borderline personality disorder, depression and post-traumatic stress disorder. environmental and social co-variates increase with lifespan so establishing cause and effect is difficult. studies in children, then, may illuminate patterns to inform current hypotheses. this paper reviews the literature on children and adolescents linking glucocorticoid gene receptor nr3c1 to the psychopathology of mental illness. findings are presented in an accessible manner to engage people less familiar with genetics and to inform frontline clinicians of this quickly growing area of research. method medline and psychinfo were searched for relevant peer-reviewed original research using the following keywords and associated mesh terms: nrc31, glucocorticoid receptor gene, methylation, epigenetics, child, adolescent, trauma, psychopathology, gene expression. result 14 studies were identified involving 5475 young people. degree of nr3c1 methylation was associated with severity of early life adversity. methylation was linked with psychopathology including borderline personality disorder, internalising symptoms and externalising symptoms with sex differences. the most consistent association was with depression. methylation seems to modulate the interaction between environment and genetics with the suggestion that the effect may be protective in some cases. however, longitudinal genetic sampling was only conducted in one study. conclusion heterogeneity of studies in the epigenetics field are discussed but should not detract from future possibilities. the hope is to identify therapeutic targets or monitor response to treatment as we work to better understand the biology of developmental psychology, mental illness and resilience. there is a growing understanding that epigenetic modifications likely change over time and clinical significance is most likely dictated by changes at multiple gene locations. thus future research may need to move away from single gene research typically employed in favour of longitudinal whole genome studies in larger population studies. it is time that clinician…”
How strangely will the Tools of a Tyrant pervert the plain Meaning of Words!
— Samuel Adams
Archon (Greek: ἄρχων, romanized: árchōn) is the Greek term for “ruler”. Cognate derivatives are, e.g., terms such as:
anarchy (etymology discussed subsequently in more detail)
According to Aristotle’s Constitution of the Athenians (78-c. 100), the power and influence of the king first devolved to the archons, and these offices were filled from the aristocracy by elections on a decennial basis. Archon Eponymos was the primary magistrate, the Polemarch referred to the head of the armed forces, and the Archon Basileus was in charge of the religious aspects of society.
Various fraternities and sororities use the title of archon or variations on it. Some Gnostic sects used this term for demons associated with the planetspheres.
3-D computer rendering of an “archon”
The term anarchy is the negation of the term archon (i.e., the negatory prefix *a). It thus means “without a ruler/master”, i.e., human beings that do not accept a master and who do not allow others to rule over them (they are not slaves to anyone). Importantly, this derivation should not be confused with “chaos or without rules”. Anarchy simply is the negation of slavery.
Niemand ist mehr Sklave, als der sich für frei hält, ohne es zu sein. ‘
~ Johann Wolfgang von Goethe
(Transl.: None are more hopelessly enslaved than those who falsely believe they are free.)
Human beings who are anarchists are thus literally beings that do not accept to be ruled by archons, i.e., they are free and cannot be ruled and suppressed by external forces (they only subordinate themselves to natural law, viz., the timeless universal metaphysical foundation of morality and ethics; cf. the Kantian categorical imperative).
Act only according to that maxim whereby you can at the same time will that it should become a universal law.
— Immanuel Kant, Grounding for the Metaphysics of Morals (1785)
In this context a quotation by the freedom fighter Malcolm X is of great pertinence.
He asked the following quintessential question concerning the highest of all virtues:
What is the price of freedom?
P.S. This does not imply that one has to die to be free, but it means that one has to be willing to risk once own life for the greatest of all goods, viz., the ultimate expression of human potential: Absolute Freedom.
If one is not willing to go “all in” one has lost the quest for freedom a priori because one is not willing to risk what it takes to achieve it. Fear is the inhibitor of freedom. Death is the mother of all fears. Ergo, overcoming the irrational fear of death is a condicio sine qua non for the obtainment of superordinate transcendental values.
Non-cooperation with evil is a sacred duty.
~ Mahatma Gandhi
Freedom comes with wisdom, intrinsically. They are inseparable, and no society wants people to be free. The communist society, the fascist society, the capitalist society, the Hindu, the Mohammedan, the Christian – no society likes people to use their own intelligence because the moment they start using their intelligence they become dangerous – dangerous to the establishment, dangerous to the people who are in power, dangerous to the “haves”; dangerous to all kinds of oppression, exploitation, suppression; dangerous to the churches, dangerous to the states, dangerous to the nations.
In fact, a wise man is afire, alive, aflame. He would like rather to die than to be enslaved. Death will not matter much to him, but he cannot sell his life to all kinds of stupidities, to all kinds of stupid people. He cannot serve them. Hence, the societies down the ages have been supplying you with false knowing. That’s the very function of your schools, colleges, universities.
They don’t serve you, remember, they serve the past, they serve the vested interests. Of course, they go on puffing your ego up bigger and bigger, they go on giving you more and more degrees. Your name becomes longer and longer, but only the name – you go on becoming shorter and shorter. A point comes where there are only certificates and the man has disappeared. First the man carries the certificates, then the certificates carry the man. The man is long dead.
‘In which case, the wisdom of a city founded on natural principles
depends entirely on its smallest group and element – the leading and
ruling element — and the knowledge that element possesses. The class
which can be expected to share in this branch of knowledge, which of all
branches of knowledge is the only one we can call wisdom, is by its nature,
apparently, the smallest class.’
Socrates in dialogue with Glaucon
‘Well, I think the first one to catch the eye is wisdom. And it seems to
have an unusual feature.’
‘What is that?’
‘It is truly wise, I think, this city we have described. It has good judg¬
ment, doesn’t it?’
‘Now this thing, judgment, is clearly knowledge of some sort. Good
decisions, I take it, are the result of knowledge, not ignorance.’
‘But our city contains many types of knowledge, of very different
‘Of course it does.’
‘Is it the knowledge possessed by its carpenters which entitles us to call
c our city wise, and say it possesses good judgment?’
‘Certainly not,’ he said. ‘That merely entitles us to call it good at car¬
‘So a city is not to be called wise because of its knowledge and judg¬
ment in making the best possible wooden furniture.’
‘How about its knowledge of making things out of bronze, or any other
knowledge of that kind?’
‘No, nothing like that,’ he said.
‘Nor the knowledge of how to grow crops from the soil, since that’s
‘So I believe.’
‘Is there, then,’ I asked, ‘among any of the citizens of this city we have
d just founded, any branch of knowledge which makes decisions about the
city as a whole – deciding on the best approach to itself and to other cities
– and not about one particular element in the city?’
‘There most certainly is.’
‘What is this knowledge, and in which group is it to be found?’
‘It is the knowledge possessed by the guardians,’ he said. ‘And it is
to be found in the rulers, whom we have just been calling the perfect
‘And what is the label you give your city on the strength of this know¬
‘I call it sound in judgment, and truly wise.’
e ‘So which do you think our city will have more of? Metalworkers, or
these true guardians?’
‘Metalworkers,’ he said. ‘Far more.’
‘Of all the groups which have a branch of knowledge of their own, and
which are identified as a group, wouldn’t the guardians be the smallest?’
‘Easily the smallest.’
‘In which case, the wisdom of a city founded on natural principles
depends entirely on its smallest group and element – the leading and
ruling element — and the knowledge that element possesses. The class
which can be expected to share in this branch of knowledge, which of all
branches of knowledge is the only one we can call wisdom, is by its nature,
apparently, the smallest class.’
Sir Francis Galton, was an English Victorian era statistician, polymath, sociologist, psychologist, anthropologist, eugenicist, tropical explorer, geographer, inventor, meteorologist, proto-geneticist, and psychometrician. He was knighted in 1909.
Galton produced over 340 papers and books. He also created the statistical concept of correlation and widely promoted regression toward the mean. He was the first to apply statistical methods to the study of human differences and inheritance of intelligence, and introduced the use of questionnaires and surveys for collecting data on human communities, which he needed for genealogical and biographical works and for his anthropometric studies.
He was a pioneer in eugenics, coining the term itself and the phrase “nature versus nurture”. His book Hereditary Genius (1869) was the first social scientific attempt to study genius and greatness.
As an investigator of the human mind, he founded psychometrics (the science of measuring mental faculties) and differential psychology and the lexical hypothesis of personality. He devised a method for classifying fingerprints that proved useful in forensic science. He also conducted research on the power of prayer, concluding it had none by its null effects on the longevity of those prayed for. His quest for the scientific principles of diverse phenomena extended even to the optimal method for making tea.
A biographical summary of the pre-eminent men of Britain grouped by profession. The extensive survey draws from information including college graduation, reputation during career, fellowships, and even known relatives. Includes discussions on findings and observations as well as referenced appendices. - Summary by Leon Harvey
„We enter the Reichstag to arm ourselves with democracy’s weapons. If democracy is foolish enough to give us free railway passes and salaries, that is its problem… We are coming neither as friends or neutrals. We come as enemies! As the wolf attacks the sheep, so come we.“ — Joseph Goebbels
„The people’s community must not be a mere phrase, but a revolutionary achievement following from the radical carrying out of the basic life needs of the working class. A ruthless battle against corruption! A war against exploitation, freedom for the workers! The elimination of all economic-capitalist influences on national policy. Maintaining a rotten economic system has nothing to do with nationalism, which is an affirmation of the Fatherland.“ — Joseph Goebbels
A lesser known fact is that Goebbels stratagems were “inspired” by Edward Bernays (who authored the book entitled “Propaganda” in 1928).
Bernays stated the following in his 1965 autobiography:
They were using my books as the basis for a destructive campaign against the Jews of Germany. This shocked me, but I knew any human activity can be used for social purposes or misused for antisocial ones.
Doob, L. W.. (1950). Goebbels’ Principles of Propaganda. Public Opinion Quarterly
“For almost a dozen years german propaganda minister goebbels was recognized as a master of his trade by those who fought and by those who acclaimed the nazi state. this article, based on both the published and unpublished portions of goebbels’ diary, summarizes the major propaganda principles which he followed.”
Meyer, M., & Welch, D.. (2006). Propaganda and the German Cinema, 1933-1945. The History Teacher
“This is the most comprehensive analysis to date of nazi film propaganda in its political, social, and economic contexts, from the pre-war cinema as it fell under the control of the propaganda minister, joseph goebbels, through to the end of the second world war. david welch studies more than one hundred films of all types, identifying those aspects of nazi ideology that were concealed in the framework of popular entertainment.”
Propaganda and mass persuasion: a historical encyclopedia, 1500 to the present. (2013). Choice Reviews Online
“This fascinating survey provides a comprehensive introduction to propaganda, its changing nature, its practitioners, and its impact on the past five centuries of world history. written by leading experts, it covers the masters of the art from joseph goebbels to mohandas gandhi and examines enormously influential works of persuasion such as ‘uncle tom’s cabin,’ techniques such as films and posters, and key concepts like black propaganda and brainwashing. case studies reveal the role of mass persuasion during the reformation, and wars throughout history. regional studies cover propaganda superpowers, such as russia, china, and the united states, as well as little-known propaganda campaigns in southeast asia, ireland, and scandinavia. the book traces the evolution of propaganda from the era of printed handbills to computer fakery, and profiles such brilliant practitioners of the art as third reich film director leni riefenstahl and 19th-century cartoonist thomas nast, whose works helped to bring the notorious boss tweed to justice.”
Herf, J.. (2005). The “jewish War”: Goebbels and the antisemitic campaigns of the Nazi propaganda ministry. Holocaust and Genocide Studies
“How the nazi leadership translated radical antisemitism into a narrative of an innocent, besieged germany striking back at an ‘international jewry’ it accused of starting and prolonging world war ii forms the subject of this study. in the nazis’ paranoid conspiracy theory ‘jewry’ comprised powers behind the scenes in london, moscow, and washington. in response to the ‘war of extermination’ that jewry had supposedly launched against germany, the nazi leadership publicly threatened to ‘exterminate’ and ‘annihilate’ the jews as an act of justified retaliation. in their minds and in their policy, the ideological connection between the ‘final solution’ and the second world war was inherent, rather than contingent. the following analysis suggests why a centuries-old hatred led to mass murder between 1941 and 1945.”
Welch, D.. (1993). Manufacturing a consensus: Nazi propaganda and the building of a ‘national community’ (volksgemeinschaft). Contemporary European History
“The point has to be made at once that any attempt to quantify public reaction to nazi propaganda is fraught with difficulties. accurate measurement of the effectiveness of nazi propaganda is weakened by the absence of public opinion surveys and the fact that, in a society that resorted so readily to coercions and terror, reported opinion did not necessarily reflect the true feelings and moods of the public, especially if these views were opposed to the regime. nevertheless, to state that public opinion in the third reich ceased to exist is not strictly true. after the nazi ‘seizure of power’ in 1933, propaganda minister joseph goebbels stressed the importance of co-ordinating propaganda with other activities. in a dictatorship, propaganda must address itself to large masses of people and attempt to move them to a uniformity of opinion and action. but the nazis also understood that propaganda is of little value in isolation. to some extent this explains why goebbels impressed on all his staff at the ministry of popular enlightenment and propaganda the imperative necessity constantly to gauge public moods. goebbels therefore regularly received (as did all the ruling élites) extraordinarily detailed reports from the secret police (sd reports) about the mood of the people and would frequently quote these in his diary. hitler, too, was familiar with these reports, and his recorded determination to avoid increasing food prices at all costs for fear that this would undermine the regime’s popularity suggests a political sensitivity to public opinion. to assure themselves of continued popular support was an unwavering concern of the nazi leadership, and of hitler and goebbels in particular.”
“F the metaphorical understanding of a situation functions in two parts irst, there is a widespread, relatively fixed set of metaphors that structure how fc we think. for example, a decision to go to war might be seen as a form o ost-benefit analysis, where war is justified …”
Steuter, E., & Wills, D.. (2008). At war with metaphor. Nueva York: Rowman and …
“BACKGROUND:pedomorphism is the retention of ancestrally juvenile traits by adults in a descendant taxon. despite its importance for evolutionary change, there are few examples of a molecular basis for this phenomenon. notothenioids represent one of the best described species flocks among marine fishes, but their diversity is currently threatened by the rapidly changing antarctic climate. notothenioid evolutionary history is characterized by parallel radiations from a benthic ancestor to pelagic predators, which was accompanied by the appearance of several pedomorphic traits, including the reduction of skeletal mineralization that resulted in increased buoyancy.results:we compared craniofacial skeletal development in two pelagic notothenioids, chaenocephalus aceratus and pleuragramma antarcticum, to that in a benthic species, notothenia coriiceps, and two outgroups, the threespine stickleback and the zebrafish. relative to these other species, pelagic notothenioids exhibited a delay in pharyngeal bone development, which was associated with discrete heterochronic shifts in skeletal gene expression that were consistent with persistence of the chondrogenic program and a delay in the osteogenic program during larval development. morphological analysis also revealed a bias toward the development of anterior and ventral elements of the notothenioid pharyngeal skeleton relative to dorsal and posterior elements.conclusions:our data support the hypothesis that early shifts in the relative timing of craniofacial skeletal gene expression may have had a significant impact on the adaptive radiation of antarctic notothenioids into pelagic habitats.”
Thibodeau, P. H., Hendricks, R. K., & Boroditsky, L.. (2017). How Linguistic Metaphor Scaffolds Reasoning. Trends in Cognitive Sciences
“Language helps people communicate and think. precise and accurate language would seem best suited to achieve these goals. but a close look at the way people actually talk reveals an abundance of apparent imprecision in the form of metaphor: ideas are ‘light bulbs’, crime is a ‘virus’, and cancer is an ‘enemy’ in a ‘war’. in this article, we review recent evidence that metaphoric language can facilitate communication and shape thinking even though it is literally false. we first discuss recent experiments showing that linguistic metaphor can guide thought and behavior. then we explore the conditions under which metaphors are most influential. throughout, we highlight theoretical and practical implications, as well as key challenges and opportunities for future research. metaphors pervade discussions of abstract concepts and complex issues: ideas are ‘light bulbs’, crime is a ‘virus’, and cancer is an ‘enemy’ in a ‘war’. at a process level, metaphors, like analogies, involve structure mapping, in which relational structure from the source domain is leveraged for thinking about the target domain. metaphors influence how people think about the topics they describe by shaping how people attend to, remember, and process information. the effects of metaphor on reasoning are not simply the result of lexical priming. metaphors can covertly influence how people think. that is, people are not always aware that they have been influenced by a metaphor.”
Hülsse, R., & Spencer, A.. (2008). The metaphor of terror: Terrorism studies and the constructivist turn. Security Dialogue
“Terrorism studies is fascinated with the terrorist actor. though this may seem natural, the present article argues that a different perspective can be fruitful. from a constructivist point of view, terrorism is a social construction. the terrorist actor is a product of discourse, and hence discourse is the logical starting point for terrorism research. in particular, it is the discourse of the terrorists’ adversaries that constitutes terrorist motivations, strategies, organizational structures and goals. hence, the article suggests a shift of perspective in terrorism studies – from an actor-centred to a discourse-centred perspective. it develops a discourse approach that emphasizes the crucial role of metaphors in the making of reality. to illustrate this approach, the metaphorical construction of al-qaeda in the german popular press in the aftermath of the terrorist attacks in new york and washington ( 2001), madrid ( 2004) and london ( 2005) is analysed. terrorism was first constituted as war, but from 2004 onwards the principal metaphor shifted from war to crime, constructing al-qaeda as a criminal rather than a military organization. this shift has transformed al-qaeda from an external to an internal threat, which has entailed a shift in counter-terrorism practices from a military to a judicial response.”
Ferrari, F.. (2007). Metaphor at work in the analysis of political discourse: Investigating a “preventive war” persuasion strategy. Discourse and Society
“The crucial historical moment represented by post 9/11 may undoubtedly be considered responsible for the subsequent hardening of american political rhetoric. and yet, the sudden increase of consensus catalysed by george w. bush and the consequences of his international policy bring his modus persuadendi up for discussion. the aim of this article is to present a framework for a metaphor-based critical analysis of persuasion in political discourse. our object of observation is george w. bush’s public speeches to the nation (2001–4). more specifically, the analysis is focused on the persuasion strategy enacted to promote the preventive war in iraq. in our approach, conceptual metaphor as related to emotion constitutes the fundamental argumentative feature and crucial tool to address the matter of persuasion in text, contributing to identifying both the ideological root and the persuasive strategy of a given discourse in the long run. synthesis of our results shows the potentialities of metaphor as a privileged cognitive tool for abstracting and constructing discourse strategies.”
Thibodeau, P., Mcclelland, J. L., & Boroditsky, L.. (2009). When a bad metaphor may not be a victimless crime : The role of metaphor in social policy. Proceedings of the Annual Meeting of the Cognitive Science Society
“Metaphors are pervasive in our discussions of abstract and complex ideas (lakoff & johnson, 1980), and have been shown to be instrumental in problem solving and building new conceptual structure (e.g., gentner & gentner, 1983; nersessian, 1992; boroditsky, 2000). in this paper we look at the role of metaphor in framing social issues. our language for discussing war, crime, politics, healthcare, and the economy is suffused with metaphor (schön, 1993; lakoff, 2002). does the way we reason about such important issues as crime, war or the economy depend on the metaphors we use to talk about these topics? might changing metaphors lead us to different conceptions and in turn different social policies? in this paper we focused on the domain of crime and asked whether two different metaphorical systems we have for talking about crime can lead people to different ways of approaching and reasoning about it. we find that framing the issue of crime metaphorically as a predator yielded systematically different suggestions for solving the crime problem than when crime was described as a virus. we then present a connectionist model that explores the mechanistic underpinnings of the role of metaphor.”
Spencer, A.. (2012). The social construction of terrorism: Media, metaphors and policy implications. Journal of International Relations and Development
“The article illustrates a constructivist understanding of studying terrorism and counter-terrorism by applying metaphor analysis to a british tabloid media discourse on terrorism between 2001 and 2005 in the sun newspaper. it identifies four conceptual metaphors constituting terrorism as a war, a crime, an uncivilised evil and as a disease, and it illustrates how these understandings make certain counter-terrorism policies such as a military response, judicial measures or immigration policies acceptable while at the same time excluding from consideration other options, such as negotiations. it thereby re-emphasises that a metaphorical understanding of political phenomena such as terrorism can give international relations insights into how certain policies become possible while others remain outside of the range of options thought to be appropriate.”
At war with metaphor: media, propaganda, and racism in the war on terror. (2013). Choice Reviews Online
“A valuable contribution to our growing understanding of the ways in which we talk ourselves into war, genocide, and other crimes against humanity. it causes us to wonder what might happen if we had the courage to deal with our rivalries and conflicts in a realistic manner rather than dehumanizing and demonizing those we consider enemies. ” —sam keen, author of faces of the enemy when photographs documenting the torture and humiliation of prisoners at abu ghraib came to the attention of a horrified public, national and international voices were raised in shock, asking how this happened. at war with metaphor offers an answer, arguing that the abuses of abu ghraib were part of a systemic continuum of dehumanization. this continuum has its roots in our public discussions of the war on terror and the metaphors through which they are repeatedly framed. arguing earnestly and incisively that these metaphors, if left unexamined, bind us into a cycle of violence that will only be intensified by a responsive violence of metaphor, erin steuter and deborah wills examine compelling examples of the images of animal, insect, and disease that inform, shape, and limit our understand-ing of the war on terror. tying these images to historical and contemporary uses of propaganda through a readable, accessible analysis of media filters, at war with metaphor vividly explores how news media, including political cartoons and talk radio, are enmeshed in these damaging, dehumanizing metaphors. analyzing media through the lenses of race and orientalism, the book invites us to hold our media and ourselves accountable for the choices we make in talking war and making enemies.”
Kövecses, Z.. (2016). Conceptual metaphor theory. In The Routledge Handbook of Metaphor and Language
“In a radical departure from theories based on digital, amodal accounts of cognition and language, lakoff and johnson (1980) proposed an account of metaphor as fundamentally conceptual, arguing that familiar linguistic metaphors are but surface manifestations of underlying conceptual relationships. they claimed that most conceptual thought is metaphorical, and conceptual domains are instantiated and expressed in families of conceptual metaphors, such as ‘more is u’, ‘emotionallyintimate is physically close’, ‘argument is war’, ‘love is a journey’, and ‘theories are buildings’. these conceptual metaphors number in the hundreds (gibbs, 1994b; lakoff and johnson, 1999), and they combine to serve as the foundation for new metaphors. for many of these families of metaphors lakoff and johnson trace the underlying metaphor to a literal concept based on embodied physical experience.”
Navaro-Yashin, Y.. (2009). Affective spaces, melancholic objects: Ruination and the production of anthropological knowledge. Journal of the Royal Anthropological Institute
“This article critically engages with recent theoretical writings on affect and non-human agency by way of studying the emotive energies discharged by properties and objects appropriated during war from members of the so-called ‘enemy’ community. the ethnographic material comes from long-term fieldwork in northern cyprus, focusing on how it feels to live with the objects and within the ruins left behind by the other, now displaced, community. i study turkish-cypriots’ relations to houses, land, and objects that they appropriated from the greek-cypriots during the war of 1974 and the subsequent partition of cyprus. my ethnographic material leads me to reflect critically on the object-centred philosophy of actor network theory and on the affective turn in the human sciences after the work of gilles deleuze. with the metaphor of ‘ruination’, i study what goes amiss in scholarly declarations of theoretical turns or shifts. instead, proposing an anthropologically engaged theory of affect through an ethnographic reflection on spatial and material melancholia, i argue that ethnography, in its most productive moments, is trans-paradigmatic. retaining what has been ruined as still needful of consideration, i suggest an approach which merges theories of affect and subjectivity as well as of language and materiality.”
Koller, V., Hardie, A., Rayson, P., & Semino, E.. (2008). Using a semantic annotation tool for the analysis of metaphor in discourse. Metaphorik.De
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“This paper describes the application of semantic annotation software for analysing metaphor in corpora of different genres. in particular, we outline three projects analysing religion and politics metaphors in corporate mission statements, the war metaphor in business magazines, and machine and living organism metaphors in a novel and in a second collection of business magazine articles. this research was guided by the hypotheses that a) semantic tags allocated by the software can correspond to source domains of metaphoric expressions, and b) that more conventional metaphors feature a source domain tag as first choice in the type’s semantic profile. the tagger was adapted to better serve the needs of metaphor research and automate to a greater extent the extraction of first choice and secondary semantic domains. two of the three studies represent re-analyses of previous manual and/or lexical corpus-based investigations, and findings indicate that semantic annotation can yield more comprehensive results. in”
Yanık, L. K.. (2009). The Metamorphosis of Metaphors of Vision: “Bridging” Turkey’s Location, Role and Identity After the End of the Cold War. Geopolitics
“During the cold war, ‘buffer’ or ‘bastion’ seemed a popular metaphor to describe turkey. after the cold war, ‘bridge,’ (and, to some extent, the ‘crossroad’) metaphor started to dominate the turkish foreign policy dışcourse. this article traces the use of ‘bridge’ metaphor in this dışcourse in the post-cold war period by the turkish foreign policy elite. it develops two arguments. first, the word bridge is a ‘metaphor of vision’ combining turkey’s perceived geographical exceptionalism with an identity and a role at the international level. as a ‘metaphor of vision,’ the employment of the word ‘bridge’ highlighted turkey’s liminality and justified some of its foreign policy actions to eurasia and then to the middle east. second, because the bridge metaphor was used in different context to justify different foreign policy choices, its meaning has changed, illustrating that metaphors are not static constructs. it concludes by sayıng that the continuous use of ‘bridge’ metaphor might reinforce turkey’s ‘liminality,’ placing turkey in a less classifiable category than the regular ‘othering’ practices.”
The individual comes face-to-face with a conspiracy so monstrous he cannot believe it exists. The American mind has not come to a realisation of the evil which has been introduced into our midst. It rejects even the assumption that human creatures could espouse a philosophy which must ultimately destroy all that is good and decent.
When morals decline and good men do nothing, evil flourishes. A society unwilling to learn from past is doomed. We must never forget our history.
John Edgar Hoover was an American law enforcement administrator and the first Director of the Federal Bureau of Investigation of the United States. He was appointed as the director of the Bureau of Investigation – the FBI’s predecessor – in 1924 and was instrumental in founding the FBI in 1935, where he remained director until his death in 1972 at the age of 77