“Brain activity can be understood, that is, has meaning, only to the extent that it is a representation of the state of the body, of the external world, or of a potential behavior. Just as it would be pointless to analyze a book by investigating the chemical composition of paper and ink, a reductionist analysis of brain activity, that is, taking it apart and analyzing its nucleic acids, enzymes, receptors, and ion channels, fails to explain what brain activity accomplishes. The neuroscience of meaning requires experiments that study brain activity as the body moves through the world or as people describe their experience.”

- Howard Fields, Setting the Stage for Pain: Allegorical Tales From Neuroscience

The English word pain is derived from the Latin word poena, meaning penalty or punishment. Because of the intrinsically intimate and subjective nature of pain, philosophers and medical providers struggle to find a definitive definition of the word. It is variable through references, authors, and times, with conceptualizations focusing alternately on the biomedical, emotional, or behavioral components of the phenomenon. The philosopher René Descartes’ mechanistic conceptualization of pain as a sensation, where the animal merely reacts to the noxious stimulus, dominated scientific and folk beliefs about pain into the mid-20th century.

 The more modern emergence of the concept of being-in-pain, which includes the subjectivity of the individual in the experience, opens the door for a bigger involvement of mental health professionals in pain management.

 International Association for the Study of Pain

 coined a new definition of pain in 1979: “unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”

 This flexible definition acknowledges the sensory, cognitive, affective, and motivational processes that influence the experience of pain and allows for a broader exploration of its subjectivity. It trades a purely neurological view for a more holistic conceptualization that considers the totality of the pain and, more importantly, of the patient.

The differentiation between acute and chronic pain has proven to be clinically useful for tailoring interventions. Traditionally, the distinction between acute and chronic pain has relied upon a single continuum of time, with the designation of an arbitrary interval as a transition point, most commonly between 3 and 6 months. Another way to characterize chronic pain is pain that extends beyond the expected period of healing—assuming one knows what that should be.

Both acute and chronic pain are major public health problems with high health care costs and resource requirements. According to a 

, the conservative estimate of the health care cost of pain is around $560 to $635 billion annually, which is significantly greater than that of heart disease, cancer, or even diabetes mellitus.

 Because of this high prevalence and significant morbidity, pain has earned the designation of “the fifth vital sign.”

Despite these tremendous expenses and heroic efforts (using sophisticated technology, biomedical advances, and ever-growing research), most pain conditions have no final options for a cure. The only potent analgesics available are opioids, which can be problematic given the current opioid epidemic in Western countries. However, with the broader and multifaceted understanding of pain, patient care has moved from a focus on eradicating pain, as based on objective pain scores, to improving the patient’s quality of life, while simultaneously decreasing pain to a level that is acceptable to the individual patient. To achieve this goal, the clinical integration of mental health providers in pain management teams has become more widespread.

The Relationship Between the Experience of Pain and Mental Health

If we agree with Ludwig Wittgenstein, PhD, who posited that “words are connected with the primitive, the natural expressions of the sensations and are used in their place,”

 it is not hard to see that even in the everyday language about pain, there exists a significant overlap between the purely physical experience of pain and the consequent subjective emotional aspects that arise with it. It might even seem that the connection transcends all elaborate philosophical theories and is deeply felt and expressed on an instinctual level. The most obvious example of the connection is that expressions like “broken-hearted” or “a slap in the face” are often used in multiple languages to describe experiences of physical as well as emotional, psychological, or even spiritual suffering.

This intimate and intricate relationship is also well understood even if one chooses to look at it from a purely neurobiological perspective. Although pain might initially originate from peripheral sensory receptors, the experience of pain is not complete without the 

modulatory involvement of the central nervous system

 Afferent stimuli from the thalamus, the limbic system, and cortical structures like the frontal lobe and the somatosensory cortex amplify or diminish the peripheral painful stimuli and add a subjective emotional component to the sensation. Functional imaging techniques and direct brain stimulation studies have demonstrated a striking overlap between central structures implicated in the 

 In addition, recent studies have described how chronic pain changes grey matter in the brain, resulting in secondary psychiatric symptoms and disorders. These studies thus emphasize a 

An individual’s experience of pain cannot be understood in a sterile context. With this conceptualization comes the possibility of applying psychological principles to the treatment of pain. Cognitive behavioral theories of pain are based on the premise that cognitions, emotions, behaviors, and physical sensations are all interrelated and exist within a particular context.

 Psychologists observe that changes in any of these areas can have wide-ranging influences through a circular effect on each other.

 illustrates how the different components of cognitive behavioral therapy (CBT) interact with each other to create vicious cycles, which in turn can cause a clinical increase in symptoms. From an interpersonal perspective, it is also clear that persistent personality traits can influence the subjective experience and expression of pain. Specific defensive and coping styles in an individual may create a particular and sometimes 

 Finally, although there is limited interest in the psychodynamic perspective of pain, multiple authors have argued that patients communicate on multiple conscious and unconscious levels through bodily manifestations, and that pain expressions hold 

 that warrant psychological and psychoanalytic exploration.

The Empirical Evidence for an Interdisciplinary Approach to Chronic Pain

From a more practical standpoint, evidence-based medicine shows a significant association between pain and mental health disorders and symptoms. There exists a statistically important comorbidity between acute and chronic pain and depressive disorders, anxiety disorders, substance use disorders, and personality disorders.

 Empirical evidence shows higher efficacy for the multidisciplinary and interdisciplinary management of pain that is based on the biopsychosocial model, which combines physical therapy, pain management by medication, patient education, ergonomic training, psychiatric treatment, and psychotherapy, among others. These interventions have shown significant results on the ratings of pain intensity scores, as well as on the quality-of-life measures that encompass both mental health and the functional impacts.

The Role of the Consultation-Liaison Psychiatrist in the Management of Pain

Consultation-liaison (C-L) psychiatrists are key members and leaders of interdisciplinary pain management teams. Psychiatry residents get the most 

 during the substance abuse/addictions (60%) and the C-L psychiatry (57%) rotations.

C-L psychiatrists are uniquely qualified to help patients with pain and play an important role in the pain management team. Although most primary care physicians and medical specialists can diagnose and initiate the treatment of psychiatric disorders, C-L subspecialists can diagnose more subtle and complex mood or anxiety disorders, substance use disorders, or personality disorders in a general medical setting. They can also participate in the pharmacological and even interventional management of pain, detect possible drug-drug interactions in these medically complex patients, and screen for possible medication side effects.

In addition, as the name of the specialty reveals, C-L psychiatrists are experts in bridging the gap between the patient and the other medical teams. They can relay messages in an empathic and understanding way and bring the goals of treatment into alignment with the patient’s values, preferences, and styles. Their integrated view of patients allows for reflection on behavioral, interpersonal, and psychodynamic formulations of the patient’s pain experience that can be communicated to the team to personalize the treatment and thus improve the quality of the care. 

 details the separate and overlapping roles of the pain specialist and the C-L psychiatrist.

Exploring the Future of C-L Psychiatry Within Pain Management Teams

 showed a national improvement of pain education in psychiatry training.

 The investigators found that more than two-thirds (70%) of program directors supported having psychiatry residents receive education and training in chronic pain management. This is a significant improvement from the less than 50% found in the 

The increase in pain management education is not limited to psychiatry residency; it also currently includes more continuing medical education (CME) focused on psychiatric aspects of pain, medication management of pain, meditation, CBT, and other strategies.

 This is particularly true for C-L psychiatrists, whose national professional organization, the 

Academy of Consultation-Liaison Psychiatry

, specifically includes CME for chronic pain as well as special interest groups for palliative medicine, addiction and toxicology, and collaborative and integrated care, among others.

Overall, the future of this integrated approach to pain with the inclusion of C-L psychiatrists looks bright. Encouraging systemic changes are starting to occur, including changes to reimbursement for medical services (meaning procedural and nonprocedural pain interventions will be more equally compensated). They also include changes to the referral processes between specialists, making the processes more efficient and allowing the emergence of bigger interdisciplinary teams.

We believe that an integrated treatment actively involves C-L psychiatry which, in the words of 

, constitutes the final missing P in the management of pain,

 and which can significantly improve health outcomes and the quality of life of this patient population.

is a consultation-liaison psychiatrist and palliative care fellow at MedStar Washington Hospital Center in Washington, DC.

is clinical and deputy scientific director of the National Institute of Mental Health and the National Institutes of Health, and acting clinical director of the National Center for Complementary and Integrative Health, all in Bethesda, MD.

Meditations on First Philosophy: With Selections From the Objections and Replies

. Moriarty M, trans. Oxford University Press; 2008.

The International Association for the Study of Pain definition of pain: as valid in 2018 as in 1979, but in need of regularly updated footnotes

3. Mehta A, Chan LS. Understanding of the concept of “total pain”: a prerequisite for pain control. 

The economic costs of pain in the United States

. Anscombe GEM, trans. Wiley-Blackwell, 1997.

Pain and suicidality: insights from reward and addiction neuroscience

A common neurobiology for pain and pleasure

Chronic pain may change the structure of the brain

New evidence for a pain personality? a critical review of the last 120 years of pain and personality

Parallel pains and dynamic dilemmas: psychodynamic considerations in approaching and managing chronic physical pain

Epidemiology of pain and relation to psychiatric disorders

Prog Neuropsychopharmacol Biol Psychiatry

13. Ilgen MA, Kleinberg F, Ignacio RV, et al. 

Noncancer pain conditions and risk of suicide

14. Scascighini L, Toma V, Dober-Spielmann S, Sprott H. 

Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes

15. Gerdle B, Åkerblom S, Brodda Jansen G, et al. 

Who benefits from multimodal rehabilitation - an exploration of pain, psychological distress, and life impacts in over 35,000 chronic pain patients identified in the Swedish Quality Registry for Pain Rehabilitation

The status of pain medicine education in psychiatry: a survey of residency training program directors

17. Majeed MH, Ali AA, Metzger S, Sudak DM. 

Pain management education and training during psychiatry residency: a report on national progress

18. Balon R, Morreale MK, Coverdale JH, et al. 

The role of psychiatric education in pain management

19. Academy of Consulation-Liaison Psychiatry. CLP 2020: delivering our vision of integrated care. 2020. Accessed March 22, 2021. 

The missing p in psychiatric training: why it is important to teach pain to psychiatrists

Articles

With a broader and multifaceted understanding of pain, patient care can move from a focus on eradicating pain, as based on objective pain scores, to improving the patient’s quality of life, while simultaneously decreasing pain to a level that is acceptable to the individual patient.

The Final “P” in Pain Management

To Recognize the role epigenetics in resilience after trauma, in both individuals who experience trauma and their descendants.

After participating in this activity, you should be better prepared to:

1. Understand how various mechanisms of epigenetics can potentially contribute to transgenerational transmission of resilience.

2. Discuss the various interpretations of the American Psychiatric Association’s definition of resilience.

3. Review the different treatment modalities that could prevent transmission of trauma.

4. Understand the potential variables that either strengthen or weaken an individual’s resilience and positive health outcomes.

This continuing education (CE) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

ACCREDITATION/CREDIT DESIGNATION/FINANCIAL SUPPORT

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership Physicians’ Education Resource®, LLC and Psychiatric Times

. Physicians’ Education Resource®, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Physicians’ Education Resource®, LLC designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This activity is funded entirely by Physicians’ Education Resource®, LLC. No commercial support was received.

This CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CE activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians’ Education Resource®, LLC.

FACULTY, STAFF, AND PLANNERS’ DISCLOSURES AND CONFLICT OF INTEREST (COI) MITIGATION

None of the staff of Physicians’ Education Resource®, LLC; Psychiatric Times

, the planners or the authors for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

; for questions concerning the accreditation of this CE activity or how to claim credit, please contact 

 and include “Transgenerational Transmission of Resilience After Catastrophic Trauma” in the subject line.

Once you have read the article, please use the following URL to evaluate and request credit: 

https://education.gotoper.com/activity/ptcme21june

. If you do not already have an account with PER®, you will be prompted to create one. You must have an account to evaluate and request credit for this activity.

 The fear, grief, social isolation, and loss associated with COVID-19 are all potentially traumatic. The ongoing pandemic makes the study of resilience mechanisms after catastrophic experience all the more timely, since what is true for the pandemic experience may be true for any traumatic experience that causes long-term isolation and helplessness. Based on the epigenetic mechanisms that promote transgenerational transmission of resilience, a growing body of research points the way to promising clinical and public health interventions. By applying what we are learning about the potential biopsychosocial mechanisms for transgenerational resilience, we can begin to design interventions to promote resilience, study their relative effectiveness, and implement them accordingly.

, approximately 70% of people worldwide will experience at least 1 traumatic event during their lifetimes, with 30.5% reporting more than 4 incidents.

 (PTSD) or other trauma- and stressor-related disorders.

 Traumatic events such as threats to one’s life, natural disasters (including the current pandemic), exposure to war and conflict, torture, discrimination, and decimation of communities serve as brutal reminders of our past. However, a clear resilience to such stressors enables the individual to thrive in spite of hardship and social isolation, as well as to endure the memories of these ordeals. The offspring of such survivors have been shown to thrive and they are often better adapted and more resilient than the previous generation.

 Awareness of potential epigenetic mechanisms may help to guide clinical and public mental health interventions to ensure that future generations are better equipped to avoid trauma- or stressor-related disorders.

Epigenetics is the study of heritable changes that occur without directly altering the nucleotide sequence of a genome. Various epigenetic processes function to determine an individual’s phenotype and control the expression of various proteins and their corresponding functional pathways. Epigenetic mechanisms of transmission include CpG islands (sites in the genome containing large numbers of CpG dinucleotide repeats), histones, and noncoding RNA. Methylation, the process of adding or removing a methyl group (–CH

), can occur at CpG islands and on histone proteins. In addition, histones can be altered in a variety of other ways, including acetylation, ubiquitination, phosphorylation, and the addition or removal of various sugars. These modifications alter the capacity for further transcription factors to express a gene.

Exposure to traumatic events can produce long-term epigenetic changes in consistent regions of the genome. 

 during episodes of trauma have long-term effects on glucocorticoid receptors, adipose tissue, the hypothalamic–pituitary–adrenal (HPA) axis, hippocampus, and amygdala.

 A combination of these factors may influence not only an individual’s own phenotype, but also how that individual and their offspring will respond to further stressors in life.

The ability to transmit epigenetic changes caused by trauma has been seen within both 

 Studies by Suter et al showed that plants such as 

 such as DNA methylation induced by life-threatening heat stress over 3 consecutive generations.

 Migicovsky et al found that when the first-generation (F

 were exposed to the same heat-induced stress as the parental generation, there was a significant decrease in the amount of global DNA methylation. The 

 developed larger leaves than the control group but became more resistant to further methylation, despite exposure to the same external stressor as the parental generation.

 Other studies have shown that various sites of 

Animal models using rodents have also shown consistent patterns of transmission across multiple generations. Dias and Ressler showed that rodents conditioned with a fear response to acetophenone gave birth to F

 (second-generation) offspring exhibiting similar fear behaviors. They determined that a persistent CpG hypomethylation of the 

 Exposure to social stressors has led to impaired rodent maternal behaviors across several generations, leading to offspring that consistently produce 

abnormal amounts of cortisone, oxytocin, and prolactin

 These findings are consistent with hormonal changes in human families who experienced similar 

Resilience is often cited as a key factor in preventing adverse changes in personality or affect in reaction to stressors experienced in one’s life.

 The American Psychiatric Association (APA) 

 as the ability to adapt in the face of adversity, trauma, tragedy, threats, or significant stress.

 Various interpretations of the APA’s definition have included an absence of psychopathology, an ability to return to homeostasis unimpaired by the traumatic event, or adaptive responses after exposure to adversity.

Some researchers have highlighted a combination of core, internal, and external resilience factors that can also contribute to how one succeeds in life.

 Core resilience is largely defined by one’s genome. Internal resilience, on the other hand, is distinguished by learned and shared behaviors that can be influenced by family, friends, and life experiences. These involve the development of healthy behaviors such as autonomy, self-control, hardiness, toughness, coping style, past experiences, resourcefulness, social competence, and grit. External resilience focuses primarily on socioecological factors, such as support from one’s community and access to social and health care services. Recognizing the different ways in which resilience can manifest and understanding these manifestations in multifactorial terms is the best method of combating and resisting traumatic adversity.

 Standardizing measures of resilience and change with respect to trauma has, however, proven to be difficult across disparate events, populations, and generations.

One measure of the impact of trauma on an individual is posttraumatic growth (PTG), which was defined in 1996 by Tedeschi and Calhoun to describe 

 Key components of affect were divided into 5 categories to measure and compare positive change due to trauma in various populations (

 in a longitudinal study of 200 Israeli prisoners of war during the 1973 Yom Kippur War. Forty-three male Israeli combat veterans were second-generation survivors of the Holocaust. Dekel measured changes in PTG among both groups of veterans, with data sets collected at 30 and 35 years after the end of the war. The study found that veterans who were offspring of Holocaust survivors scored lower on PTG and had a lower likelihood of developing PTSD than veterans in the control group. A lower score on PTG as well as PTSD symptoms may indicate resilience to change as a result of trauma, whereas the effects of trauma may have been more pronounced in the control group (who were not offspring of Holocaust survivors). Whether a genetic component was responsible was not clear, but the authors proposed it as an area of further study.

Our genome and epigenetics may provide explanations of human resilience in the face of trauma. For example, the FK506-binding protein 51 (FKBP5) is a biomolecule that appears to modulate our reaction to stress and ability to exhibit resilience. The 

 for glucocorticoid receptors on chromosome 6 (6p21.31).

 Research has shown that behavioral responses to stress are 

—as is the HPA axis—and can be affected by factors such as exposure to trauma.

 In animal studies, mice with the gene for 

 removed show a stronger resilience to stressors by exhibiting a lowered fear response.

In another study of Holocaust survivors, 

 looked at the epigenetic mechanisms of transmission of the 

 gene, focusing primarily on DNA methylation of the CpG sites located in and proximal to intron 7 of 

 Methylation of bin 3/site 6 was found to be 10% higher in Holocaust survivors, but methylation of the same bin 3/site 6 was 7.7% lower in the offspring of Holocaust survivors than in the control groups. These findings were consistent when controlling for lifetime PTSD in the offspring and for possible childhood trauma. The 30-year age difference between the parents and their offspring could explain the differences in methylation; however, Yehuda et al noted that even a 1% to 2% difference in gene methylation can significantly alter gene expression.

 Furthermore, the study of Miller et al showed that methylation of specific CpG sites of 

 Greater methylation of the CpG site cg07485685 decreased PTSD symptom severity while increasing resiliency scores measured via the Brief Resilience Scale. A PTG inventory was also used to measure any positive changes as a result of trauma. Lower levels of PTG after trauma were associated with methylation of the same CpG site cg07485685 on

. These findings are consistent with the lower scores on PTG and lower levels of PTSD found in the study of Dekel et al in 2013.

Genes that are responsible for regulation of the HPA axis may also confer resilience to trauma. For example, multiple studies have found that childhood trauma and mistreatment are a risk factor for methylation of the human glucocorticoid receptor (NR3C1) gene and changes to the HPA axis.

 in newborn infants has been linked to prenatal exposure to stress.

 For instance, Perroud and colleagues examined the epigenetic changes in pregnant Tutsi survivors of the Rwandan genocide and their offspring. The mothers and their offspring were found to have 

Variations in single-nucleotide polymorphisms (SNPs), specifically rs10482672, were also found to increase the risk of psychopathology. 

 found that children who were identified as having this genotype were more vulnerable to developing substance abuse and antisocial behavior under adverse conditions, but at the same time were more likely to benefit from advantageous conditions.

 Children were placed in a fast-track program, which fostered the development of emotional regulation, self-control, and other treatments to minimize the effects of harsh parenting and violent environment. Those who received early intervention to reduce risks of developing psychopathology had a significantly decreased risk of external psychopathology via substance abuse or antisocial behavior later in life. Those in the control group, who had SNP rs10482672 but did not receive early treatment, had a higher likelihood of external psychopathology by the time they reached 25 years of age.

 In 2020, Miller et al also found methylation of 5 CpG sites in the 

 gene that were significantly linked with resilience.

 Three CpG sites were correlated with an increased score (indicating higher resilience) on the Brief Resilience Scale, whereas 2 CpG sites were correlated with decreased resilience. Authors in all studies noted the need for larger sample sizes as well as additional longitudinal studies.

What can be done to prevent transmission of past trauma to future generations? Studies have shown that nonpharmacological treatment of trauma- and stressor-related disorders can induce epigenetic changes in the genome responsible for the HPA axis.

 Roberts et al examined the methylation of 

 before and after exposure-based cognitive behavioral therapy (CBT) in patients previously diagnosed with agoraphobia. Those who reported benefits from CBT after completing treatment were found to have lower levels of methylation at a CpG island at intron 7 of 

. The severity of symptoms was reduced by an average of 69.5% in those who received exposure-based CBT, which correlated with the decrease in methylation. Individuals who reported little change from CBT were found to have either no significant changes or even increases in methylation of CpG islands at intron 7 of 

Bishop et al found similar results in patients with PTSD who received mindfulness-based stress reduction interventions. These patients showed levels of methylation of intron 7 of 

 significantly different after intervention compared with initial levels. Those who responded to treatment, as indicated by a 10-point drop in PTSD severity via a PTSD checklist, had 

significantly decreased levels of methylation

, whereas those who did not respond to treatment showed higher levels of methylation in a different site at bin 2 of 

 Mindfulness and techniques that encourage thought and understanding, such as CBT and storytelling, might 

Family and community play a strong role in enhancing an individual’s resilience. 

Fundamental building blocks for resilience

 include a secure foundation and promotion of self-esteem and self-efficacy.

 Strong bonds with caregivers and shared values and religious beliefs that find meaning in suffering are protective against adverse effects of trauma in children. Longitudinal studies of the effects of social relationships have found that support from family, friends, colleagues, and community leaders leads to a reduction in psychological distress, as well as a more rapid recovery from the effects of trauma.

Likewise, the World Health Organization has found that the arts have contributed to the improvement of public health. Music, art, dance, and communication through storytelling about past events at an early age not only reduce anxiety but also protect against cognitive decline later in life. Exposure to and involvement with the arts “trigger psychological, physiological, social, and behavioral responses” associated with positive health outcomes that may be linked to 

Exercise has long been associated with various health benefits and has been documented to be valuable for regulating reactions to stress, sleep, and resilience to mood disorders.

 In animal models, exercise serves a protective role in lowering the rates of 

 Mice who exercised via long-term wheel running had increased levels of galanin, a neuropeptide that has been 

 as well as the regulation of norepinephrine and other products of the HPA axis.

 in mice was also consistent with a significant increase in stress resilience, inducing methylation of 

 and downregulating noncoding RNA such as microRNA-124 in areas such as the hippocampus.

 Epigenetic changes as a result of exercise improved cognition in the mice of the parental generation as well as subsequent offspring.

 have correlated with findings in human studies, as mothers who exercised regularly before and during pregnancy had offspring who achieved higher levels of academic performance, excelling in language and math and having higher overall grade point averages.

 Other factors, such as shared environments and positive parental influences, may have played a part in the success, but they do not account for epigenetic differences in DNA seen at birth. Regular moderate exercise seems to confer a protective effect that enables future generations to adapt to and thrive in their new world.

Patients diagnosed with trauma- and stressor-related disorders show evidence of dysregulation of their HPA axis, resulting in persistent personality changes.

 The diagnosis of Enduring Personality Change After Catastrophic Experience (EPCACE) is defined as an enduring personality change lasting at least 2 years that a patient experiences following a catastrophic stressor (ICD-10). Thus, the presence or absence of a diagnosis of EPCACE may serve as a predictive factor for resilience and vulnerability in the face of trauma.

 Long-lasting epigenetic changes may present themselves as enduring 

 Those diagnosed with EPCACE often are socially isolated, fearing the stigma of their suffering. This may lead to a vicious cycle by which epigenetic effects are compounded and changes further solidified until a persistent and permanent change in personality has taken place (

As the COVID-19 pandemic waxes and wanes and the fear, grief, and stress of the pandemic itself and preventive social isolation measures take their toll, it is paramount that we identify the most trauma-vulnerable patients and populations early on. Individuals 

 and other trauma-related disorders are heritably linked to autoimmune diseases, dementia, schizophrenia, bipolar, and major depressive disorders.

 Chronic stress and isolation continue to be correlated with increased risks for anxiety and depression, leading to higher rates of infection and early mortality.

Fortunately, those who are most vulnerable to isolation and demoralization are often most likely to benefit from preventive intervention,

 the need for which is all too evident in our current circumstances. At the same time, there is a lack of transgenerational studies of, and a dearth of instruments to reliably study, the effectiveness of interventions to promote resilience in communities.

With the COVID-19 pandemic coming to an end, it is time to apply what we know about potential biopsychosocial mechanisms for transgenerational resilience in order to design alternative interventions to promote such resilience. We can then study the relative effectiveness of such interventions and support those that are most effective, in keeping with considerations of social justice and equity. Otherwise, even as we win the battle to defeat COVID-19, we may lose the transgenerational war to 

is a second-year medical student at Pacific Northwest University Health Sciences. 

is an assistant professor of psychiatry in the Oregon Health & Science University (OHSU) School of Medicine.

is the cofounder of the Program in Psychiatry and the Law at Harvard Medical School and President of the American Unit of the UNESCO Bioethics Chair (Haifa). He is the coauthor of

 Medical Choices, Medical Chances: How Patients, Families, and Physicians Can Cope with Uncertainty 

(1981/1990). He practices clinical and forensic psychiatry and risk management in Cambridge, Massachusetts.

The authors thank Raquelle Mesholam-Gately, PhD, and Anthony Cunningham, PhD, for their thoughtful reading of an earlier draft.

1. Knipscheer J, Sleijpen M, Frank L, et al. 

Prevalence of potentially traumatic events, other life events and subsequent reactions indicative for posttraumatic stress disorder in the Netherlands: a general population study based on the trauma screening questionnaire.

The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium

3. Mehta D, Miller O, Bruenig D, David G, Shakespeare-Finch J. 

A systematic review of DNA methylation and gene expression studies in posttraumatic stress disorder, posttraumatic growth, and resilience

Transgenerational transmission of trauma and resilience: a qualitative study with Brazilian offspring of Holocaust survivors

5. Leon GR, Butcher JN, Kleinman M, et al. 

Survivors of the Holocaust and their children: current status and adjustment

6. Rieck M. The psychological state of Holocaust survivors’ offspring: an epidemiological and psychodiagnostic study. 

7. Sagi-Schwartz A, Van IJzendoorn MH, Grossmann KE, et al. 

Attachment and traumatic stress in female holocaust child survivors and their daughters

How can we begin to design interventions to promote resilience, study their relative effectiveness, and implement them accordingly?

Vol 38, Issue 6

The Final “P” in Pain Management

Transgenerational Transmission of Resilience After Catastrophic Trauma

Pride

New Approaches and Considerations to Cancer and Suicide

Exploring the Epigenetic Paradigm Shift

First, Do No Harm: New Canadian Law Allows for Assisted Suicide for Patients with Psychiatric Disorders