Human responses to stress and trauma vary widely. Some people develop trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD) and depression; others develop mild to ...moderate psychological symptoms that resolve rapidly; still others report no new psychological symptoms in response to traumatic stress. Individual variability in how animals and humans respond to stress and trauma depends on numerous genetic, developmental, cognitive, psychological, and neurobiological risk and protective factors.
AbstractRecent scientific and technological advances have brought us closer to being able to apply a true biopsychosocial approach to the study of resilience in humans. Decades of research have ...identified a range of psychosocial protective factors in the face of stress and trauma. Progress in resilience research is now advancing our understanding of the biology underlying these protective factors at multiple phenotypic levels, including stress response systems, neural circuitry function, and immune responses, in interaction with genetic factors. It is becoming clear that resilience involves active and unique biological processes that buffer the organism against the impact of stress, not simply involve a reversal of pathological mechanisms. Here, we provide an overview of recent progress in the field, highlighting key psychosocial milestones and accompanying biological changes during development, and into adulthood and old age. Continued advances in our understanding of psychological, social, and biological determinants of resilience will contribute to the development of novel interventions and help optimize the type and timing of intervention for those most at risk, resulting in a possible new framework for enhancing resilience across the life span.
Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent ...research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress.
Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of ...depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy.
Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy.
All individuals experience stressful life events, and up to 84% of the general population will experience at least one potentially traumatic event. In some cases, acute or chronic stressors lead to ...the development of posttraumatic stress disorder (PTSD) or other psychopathology; however, the majority of people are resilient to such effects. Resilience is the ability to adapt successfully in the face of stress and adversity. A wealth of research has begun to identify the genetic, epigenetic, neural, and environmental underpinnings of resilience, and has indicated that resilience is mediated by adaptive changes encompassing several environmental factors, neural circuits, numerous neurotransmitters, and molecular pathways. The first part of this review focuses on recent findings regarding the genetic, epigenetic, developmental, psychosocial, and neurochemical factors as well as neural circuits and molecular pathways that underlie the development of resilience. Emerging and exciting areas of research and novel methodological approaches, including genome-wide gene expression studies, immune, endocannabinoid, oxytocin, and glutamatergic systems, are explored to help delineate innovative mechanisms that may contribute to resilience. The second part reviews several interventions and preventative approaches designed to enhance resilience in both developmental and adult populations. Specifically, the review will delineate approaches aimed to bolster resilience in individuals with PTSD. Furthermore, we discuss novel pharmacologic approaches, including the N-methyl-d-aspartate (NMDA) receptor ketamine and neuropeptide Y (NPY), as exciting new prospects for not only the treatment of PTSD but as new targets to enhance resilience. Our growing understanding of resilience and interventions will hopefully lead to the development of new strategies for not just treating PTSD but also screening and early identification of at-risk youth and adults. Taken together, efforts aimed at dissemination and implementation of novel interventions to enhance resilience will have to keep pace with the growth of new preventive and treatment strategies.
Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled ...trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD.
Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures.
The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events.
This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.
Depression is a common problem in patients with cardiovascular disease (CVD) and is associated with increased mortality, excess disability, greater health care expenditures, and reduced quality of ...life. Depression is present in 1 of 5 patients with coronary artery disease, peripheral artery disease, and heart failure. Depression complicates the optimal management of CVD by worsening cardiovascular risk factors and decreasing adherence to healthy lifestyles and evidence-based medical therapies. As such, standardized screening pathways for depression in patients with CVD offer the potential for early identification and optimal management of depression to improve health outcomes. Unfortunately, the burden of depression in patients with CVD is under-recognized; as a result, screening and management strategies targeting depression have been poorly implemented in patients with CVD. In this review, the authors discuss a practical approach for the screening and management of depression in patients with CVD.
Resilience Southwick, Steven M.; Charney, Dennis S.
Resilience,
07/2012
eBook, Book Chapter
Many of us will be struck by one or more major traumas sometime in our lives. Perhaps you have been a victim of sexual abuse, domestic violence or assault. Perhaps you were involved in a serious car ...accident. Perhaps you are a combat veteran. Maybe you were on the beach in Thailand during a tsunami, or in New Orleans during Hurricane Katrina. Or maybe, you are among the millions who have suffered a debilitating disease, lost a loved one or lost your job. This inspiring book identifies ten key ways to weather and bounce back from stress and trauma. Incorporating the latest scientific research and dozens of interviews with trauma survivors, it provides a practical guide to building emotional, mental and physical resilience. Written by experts in post-traumatic stress, this book provides a vital and successful roadmap for overcoming the adversities we all face at some point in our lives.
Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded ...a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.
This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).
The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval CI, 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.
Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
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