Chronic stress can lead to depression through several pathways in the body and brain. The stress response involves the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, which elevate cortisol and catecholamine levels. Over time, prolonged activation of these systems due to stress can result in allostatic load, damaging the body and brain through effects on inflammatory and immune responses. This dysregulation of stress mediators is associated with increased risk of depression as well as medical conditions like heart disease and metabolic syndrome. Meditation may help reduce stress's harmful impacts through effects on the brain's opioid and stress response systems.
Martha Stark MD – 8 Oct 2021 – The Transformative Power of Optimal Stress – P...Martha Stark MD
The therapeutic provision of “optimal stress” – against the backdrop of an empathically attuned and authentically engaged therapy relationship – is sometimes the magic ingredient needed to overcome the inherent resistance to change so frequently encountered in patients with longstanding emotional injuries. Ongoing challenge will destabilize and support will then prompt restabilization at ever-higher levels of resilience and adaptive capacity.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
Stress is a common problem that affects mental and physical well-being. It arises from demands exceeding one's ability to cope. Stress was first studied scientifically by Hans Selye in the 1930s. It has physiological and cognitive components. Physiologically, stress activates the HPA axis and sympathetic nervous system. Cognitively, one's appraisal of a situation as threatening leads to stress. Chronic stress weakens the immune system and increases inflammation, risking disease. Managing stress requires identifying stressors and employing problem-focused or emotion-focused coping strategies.
Noise in multiple sclerosis: unwanted and necessaryMutiple Sclerosis
Isabella Bordi, Vito A G Ricigliano, Renato Umeton, Giovanni Ristori, Francesca Grassi, Andrea Crisanti, Alfonso Sutera, and Marco Salvetti
As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression "noise") can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy.
The document discusses the history and theories of stress. It describes Hans Selye's theory of the general adaptation syndrome consisting of alarm, resistance, and exhaustion stages. Walter Cannon's work on homeostasis and the fight or flight response is also discussed. Theories by Richard Lazarus on cognitive appraisal of stressors and physiological responses involving the sympathetic nervous system, HPA axis, and immune system are summarized.
Martha Stark MD – 10 Dec 2016 – Limbic Kindling and Hypersensitivity to Stres...Martha Stark MD
Over the course of the decades, my own approach has become much more integrative and holistic – one that appreciates the complex interdependence of mind and body and the critical role played by the impact of stress on the MindBodyMatrix.
The living system – the ground regulation system – the divine matrix – the web of life – a liquid crystal through which information and energy flow.
More specifically, I will be speaking to the role played by limbic kindling and the resultant hypersensitivity to stress that is a hallmark of depressed patients.
The document discusses stress and its pathophysiological effects on the body. It defines stress as the non-specific response of the body to any demand, whether pleasant or unpleasant. This response involves two main systems - the sympathetic nervous system and the HPA axis. Prolonged or chronic stress can lead to damage of physiological systems and eventually death. It also discusses how social factors like poverty and lack of social support can increase stress levels and impact health.
Martha Stark MD – 27 Oct 2017 – The Transformative Power of Optimal Stress.pptxMartha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and inherent capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unmastered early-on relational traumas” replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
Chronic stress can lead to depression through several pathways in the body and brain. The stress response involves the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, which elevate cortisol and catecholamine levels. Over time, prolonged activation of these systems due to stress can result in allostatic load, damaging the body and brain through effects on inflammatory and immune responses. This dysregulation of stress mediators is associated with increased risk of depression as well as medical conditions like heart disease and metabolic syndrome. Meditation may help reduce stress's harmful impacts through effects on the brain's opioid and stress response systems.
Martha Stark MD – 8 Oct 2021 – The Transformative Power of Optimal Stress – P...Martha Stark MD
The therapeutic provision of “optimal stress” – against the backdrop of an empathically attuned and authentically engaged therapy relationship – is sometimes the magic ingredient needed to overcome the inherent resistance to change so frequently encountered in patients with longstanding emotional injuries. Ongoing challenge will destabilize and support will then prompt restabilization at ever-higher levels of resilience and adaptive capacity.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
Stress is a common problem that affects mental and physical well-being. It arises from demands exceeding one's ability to cope. Stress was first studied scientifically by Hans Selye in the 1930s. It has physiological and cognitive components. Physiologically, stress activates the HPA axis and sympathetic nervous system. Cognitively, one's appraisal of a situation as threatening leads to stress. Chronic stress weakens the immune system and increases inflammation, risking disease. Managing stress requires identifying stressors and employing problem-focused or emotion-focused coping strategies.
Noise in multiple sclerosis: unwanted and necessaryMutiple Sclerosis
Isabella Bordi, Vito A G Ricigliano, Renato Umeton, Giovanni Ristori, Francesca Grassi, Andrea Crisanti, Alfonso Sutera, and Marco Salvetti
As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression "noise") can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy.
The document discusses the history and theories of stress. It describes Hans Selye's theory of the general adaptation syndrome consisting of alarm, resistance, and exhaustion stages. Walter Cannon's work on homeostasis and the fight or flight response is also discussed. Theories by Richard Lazarus on cognitive appraisal of stressors and physiological responses involving the sympathetic nervous system, HPA axis, and immune system are summarized.
Martha Stark MD – 10 Dec 2016 – Limbic Kindling and Hypersensitivity to Stres...Martha Stark MD
Over the course of the decades, my own approach has become much more integrative and holistic – one that appreciates the complex interdependence of mind and body and the critical role played by the impact of stress on the MindBodyMatrix.
The living system – the ground regulation system – the divine matrix – the web of life – a liquid crystal through which information and energy flow.
More specifically, I will be speaking to the role played by limbic kindling and the resultant hypersensitivity to stress that is a hallmark of depressed patients.
The document discusses stress and its pathophysiological effects on the body. It defines stress as the non-specific response of the body to any demand, whether pleasant or unpleasant. This response involves two main systems - the sympathetic nervous system and the HPA axis. Prolonged or chronic stress can lead to damage of physiological systems and eventually death. It also discusses how social factors like poverty and lack of social support can increase stress levels and impact health.
Martha Stark MD – 27 Oct 2017 – The Transformative Power of Optimal Stress.pptxMartha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and inherent capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unmastered early-on relational traumas” replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
This document discusses how the nervous system controls and regulates every system in the body. It explains how problems with the nervous system can lead to issues like neuropathy, heart/blood pressure problems, digestive issues, hormone imbalances, and more. It emphasizes looking at the whole person and nervous system rather than just symptoms. Maintaining a healthy nervous system involves diet, exercise, rest, and chiropractic care to allow the body to function properly.
Martha Stark MD – 16 Jun 2017 – The Transformative Power of Optimal Stress.pptxMartha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and then channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness" and "actualization of potential," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unresolved childhood dramas" replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
Psychosomatic medicine in relation to cardiovascular diseaseSantanu Ghosh
This document discusses the relationship between psychosomatic medicine and cardiovascular disease. It covers topics such as the concepts of psychosomatic medicine including the biopsychosocial model, stress theory, and psychoneuroimmunological basis of disease. It also discusses psychiatric disorders that can be associated with heart disease such as depression, anxiety, and how they may impact cardiovascular health. The document outlines diagnostic issues and management approaches including consultation-liaison psychiatry, psychotherapy, pharmacotherapy, and stress management.
This document discusses the relationship between stress and disease. It describes how stress triggers the hypothalamic-pituitary-adrenal axis and cortisol release. Elevated cortisol levels over long periods can suppress the immune system and increase risks for diseases like obesity, hypertension, and diabetes. Stress also increases catecholamine and cytokine production, which have pro-inflammatory effects and can further impact immune function and health. The aging process may exacerbate these stress responses through changes in the limbic system, hormones, inflammation, and other physiological factors.
The document discusses various aspects of stress, including:
1. The physiology of stress including the general adaptation syndrome, hypothalamic-pituitary-adrenal system, and sympathomedullary pathway.
2. The role of stress in illness and how it can lead to immunosuppression and cardiovascular disorders.
3. Sources of stress such as life changes, daily hassles, and workplace stress. Research on measuring stress through self-report scales and physiological measures is also examined.
Martha Stark MD – 11 Feb 2023 – The Art and The Science of Interpretation.pptxMartha Stark MD
From moment to moment, we are continuously deciding how best to position ourselves in relation to our patients and the maladaptive defenses to which they cling – once necessary for them to survive but now interfering with their ability to thrive.
On the one hand, we have respect for our patients and for the choices, no matter how unhealthy, that they find themselves continuously making; on the other hand, we have a vision of who we think they could be were they but able/willing to make healthier choices for themselves. Indeed, we are always struggling to find an optimal balance within ourselves between accepting the reality of who our patients are and wanting them to change.
Whether we are working within the interpretive framework of classical psychoanalytic theory, the corrective-provision framework of self psychology, or the intersubjective framework of contemporary relational theory, we are therefore ever busy deciding – whether consciously or unconsciously – if we should “be with our patients where they are” (Akhtar’s homeostatic attunement) or “direct their attention to elsewhere” (Akhtar’s disruptive attunement) – a critically important balance that is needed if the analytic endeavor is to be advanced.
To demonstrate the translation of these theoretical constructs into clinical practice, I will be proposing a number of broadly applicable “template” interventions that juxtapose both the patient’s “defensive need” to maintain “same old same old” and the patient’s “adaptive capacity” to allow for “something new, different, and better.” Clinical vignettes will be offered that demonstrate judicious and ongoing use of these “optimally stressful” interventions that alternately support and challenge the defense, thereby galvanizing advancement of the patient, over time, from psychological rigidity to psychological flexibility.
If indeed the therapeutic goal is deep and sustained psychodynamic change, then it behooves all of us to become comfortable with the concept of provoking – with our interventions – enough incentivizing anxiety and destabilizing stress within our patients that there will be both impetus and opportunity for them, ultimately, to transform rigid defense into more flexible adaptation. The strategic formulation of interpretations specifically designed to generate this optimal stress is indeed both an art and a science.
This document provides a summary of a presentation by Dr. Bipin Jethani on revisiting Samuel Hahnemann through his works and principles. Some of the key points made in the presentation include: Hahnemann was ahead of his time in areas like psychosomatic medicine, public health, contagious disease, and experimental pharmacology. The presentation also discusses Hahnemann's appreciation of areas like surgery, allopathy in emergencies, and the material and dynamic components of the human body. Clinical cases are presented to illustrate Hahnemannian concepts and pearls of wisdom are shared from Hahnemann's writings.
Martha Stark MD – Oct 2019 – The Transformative Power of Optimal Stress – Pre...Martha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and inherent capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unmastered early-on relational traumas” replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
Martha Stark MD – 13 Apr 2023 – The Therapeutic Use of Optimal Stress to Prov...Martha Stark MD
The therapeutic provision of “optimal stress” – against the backdrop of an empathically attuned and authentically engaged therapy relationship – is sometimes the magic ingredient needed to overcome the inherent resistance to change so frequently encountered in patients with longstanding emotional injuries. Ongoing challenge will destabilize and support will then prompt restabilization at ever-higher levels of resilience and adaptive capacity.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
[KINDLE]⚡book✔ Infectious Behavior Brain-Immune Connections in Autism Schizo...nonvoluaswer
In Infectious Behavior neurobiologist Paul Patterson examines the involvement of the immune system in autism schizophrenia and major depressive disorder. Although genetic approaches to these diseases have garnered the lion's share of publicity and funding scientists are uncovering evidence of the important avenues of communication between the brain and the immune system and their involvement in mental illness. Patterson focuses on this brainimmune crosstalk exploring the possibility that it may help us understand the causes of these common but still mysterious diseases. The heart of this engaging book accessible to nonscientists concerns the involvement of the immune systems of the pregnant
This is a presentation made on stress and related problems related to physiological aspects of it. It also explains General Adaption Syndrome i.e our bodies response to stressor hormone like Oxytocin and cortisol in basic 3 stages, also some of the sympathetic and parasympathetic functions. It gives you general idea about the "Stress curve" .
This document summarizes a feasibility analysis for a proposed method to control diseases by manipulating the relationship between the immune and nervous systems using bioelectronic techniques. It first provides background on the costs of diseases related to immune response and the potential market opportunity. It then reviews the physiology of interactions between the central/peripheral nervous, endocrine and immune systems, focusing on the role of the vagus nerve in immunomodulation. Specifically, it discusses how vagus nerve stimulation has anti-inflammatory effects and been shown to ameliorate systemic inflammation in previous research. The document proposes developing a device to help gain more objective results from neuromodulation techniques for immune applications.
This document provides an overview of stress, including its definition, types, causes, biological mechanisms, effects, and management. It defines stress as the body's reaction to excessive demands or pressures, and notes there are three main types: acute, episodic, and chronic stress. The biological mechanisms of stress involve the hypothalamus-pituitary-adrenal axis activating a stress response through the release of cortisol and other hormones. Prolonged stress can negatively impact physical and mental health. Effective stress management includes identifying stressors, adapting coping strategies, and accepting what cannot be changed.
Stress is the body's response to any demand placed on it and can be caused by both external and internal factors. The body responds to stress through the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, which trigger the release of hormones like cortisol and neurotransmitters like epinephrine that prepare the body for the fight-or-flight response. While stress responses evolved to be helpful in the short term, prolonged stress over time can negatively impact health and increase risks of diseases and unhealthy behaviors. Managing stress through exercise, meditation, relaxation techniques, and maintaining social support networks can help mitigate stress's harmful effects.
Chronic diseases can be influenced by and influence chronic stress through complex relationships. The document discusses how stress may exacerbate chronic diseases like multiple sclerosis through effects on the immune system. It prompts the reader to reflect on a chronic disease and how it could impact or be impacted by stress, and to propose a behavioral intervention that may help treat the disease by addressing stress. The discussion suggests taking a holistic perspective to better understand and manage relationships between stress and chronic illness.
MIGRAINE A DEFICIENCY DISORDER OF NEUROCHEMICALSpharmaindexing
This document discusses migraine, a common type of headache. It provides background on the history of migraine and theories about its pathophysiology. Migraine is considered a neurovascular disorder involving activation of the trigeminal nerve and blood vessel dilation in the brain. It affects around 12% of the population and is more prevalent in females. The document reviews risk factors, symptoms, classification of migraine types, and potential mechanisms in the brain involved in aura and headache pain.
Immune Factors in Mental Diagnoses.docxstudywriters
The document discusses the theory that certain mental health diagnoses may be linked to dysfunctional immune cells. These diagnoses include Alzheimer's disease, autism, bipolar disorder, major depression, obsessive compulsive disorder, and schizophrenia. Research is still early but exploring these psychoneuroimmunology links. The implications could impact treatment approaches if more connections are found between mental health and immune system issues. The author is asked to select a mental health diagnosis other than depression, explain related immune theories and propose two cognitive/behavioral interventions that could help immune function for that diagnosis.
This document summarizes a research article that investigated whether disrupting the circadian rhythms of rats by exposing them to a 22-hour light-dark cycle leads to depressive-like behaviors. The study found that rats exposed to the disrupted light cycle showed signs of depression, including decreased pleasure-seeking behaviors, sexual dysfunction, and increased immobility in tests for depressive symptoms. Analysis also revealed changes in brain chemistry related to mood. The results support the hypothesis that misalignment of circadian rhythms due to problems with the brain's central clock may contribute to the development of depression.
This document discusses the potential shared pathophysiological mechanism of dysregulated inflammation linking neurocognitive and behavioral dysfunction in individuals with HIV, depression, and chronic stress. It provides background on psychoneuroimmunology and highlights classic studies showing interactions between behavior, the immune system, and nervous system. Emotions are discussed as being central to these interactions through their physiological effects in the brain and ability to aid memory formation and physiological regulation. Individual differences, genetics, and social contexts can impact these psychoneuroimmunological relationships.
Martha Stark MD – Clinical Interventions – Chapter 2 of my WORKING WITH RESIS...Martha Stark MD
In order to demonstrate the ways in which the concepts of conflict and resistance can be applied to the clinical situation, let us think about the following three situations:
1. The patient is obviously upset but is trying hard not to cry.
2. The patient knows that her therapist will not laugh at her but finds herself fearing that the therapist might.
3. The patient is upset with her therapist and knows, on some level, that she must eventually confront the reality of just how disappointed she really is, but she would like to think that she could get better without having to do that.
In our interventions in these three situations of conflict, we have three options, and we must decide from moment to moment which to choose.
Martha Stark MD – Model 1 – The Interpretive Perspective of Classical Psychoa...Martha Stark MD
If deep and enduring psychodynamic change is the ultimate goal of treatment, then periodically juxtaposing seemingly contradictory “forces” (Hegel’s thesis and antithesis) will eventually jump-start the patient’s “adaptive recovery” by creating optimally stressful, growth-incentivizing “mismatch experiences.”
I will be proposing use of something to which I refer as a “conflict statement” – a clinically useful and almost universally applicable therapeutic intervention strategically designed to target internal conflictedness between anxiety-provoking (but ultimately growth-promoting) forces pressing “yes” and anxiety-relieving (but growth-impeding) resistant counterforces defending “no.”
The stress and strain of the “destabilizing dissonance” hereby created will provide the “therapeutic leverage” needed for the patient gradually, over time, to relinquish the tenacity of her rigid attachment to the defense in favor of a more flexible adaptation – a “compromise position” that will “reconcile their common truths” (Hegel’s synthesis) and transform conflict into collaboration.
The strategic construction of conflict statements requires of the therapist that she be able both to support the patient’s defense by “being with the patient where she is” and to challenge the patient’s defense by “directing the patient’s attention to where the therapist would want her to go.” I will be offering specific clinical examples to demonstrate the impact of these powerfully impactful psychotherapeutic interventions. No pain, no gain…
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This document discusses how the nervous system controls and regulates every system in the body. It explains how problems with the nervous system can lead to issues like neuropathy, heart/blood pressure problems, digestive issues, hormone imbalances, and more. It emphasizes looking at the whole person and nervous system rather than just symptoms. Maintaining a healthy nervous system involves diet, exercise, rest, and chiropractic care to allow the body to function properly.
Martha Stark MD – 16 Jun 2017 – The Transformative Power of Optimal Stress.pptxMartha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and then channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness" and "actualization of potential," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unresolved childhood dramas" replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
Psychosomatic medicine in relation to cardiovascular diseaseSantanu Ghosh
This document discusses the relationship between psychosomatic medicine and cardiovascular disease. It covers topics such as the concepts of psychosomatic medicine including the biopsychosocial model, stress theory, and psychoneuroimmunological basis of disease. It also discusses psychiatric disorders that can be associated with heart disease such as depression, anxiety, and how they may impact cardiovascular health. The document outlines diagnostic issues and management approaches including consultation-liaison psychiatry, psychotherapy, pharmacotherapy, and stress management.
This document discusses the relationship between stress and disease. It describes how stress triggers the hypothalamic-pituitary-adrenal axis and cortisol release. Elevated cortisol levels over long periods can suppress the immune system and increase risks for diseases like obesity, hypertension, and diabetes. Stress also increases catecholamine and cytokine production, which have pro-inflammatory effects and can further impact immune function and health. The aging process may exacerbate these stress responses through changes in the limbic system, hormones, inflammation, and other physiological factors.
The document discusses various aspects of stress, including:
1. The physiology of stress including the general adaptation syndrome, hypothalamic-pituitary-adrenal system, and sympathomedullary pathway.
2. The role of stress in illness and how it can lead to immunosuppression and cardiovascular disorders.
3. Sources of stress such as life changes, daily hassles, and workplace stress. Research on measuring stress through self-report scales and physiological measures is also examined.
Martha Stark MD – 11 Feb 2023 – The Art and The Science of Interpretation.pptxMartha Stark MD
From moment to moment, we are continuously deciding how best to position ourselves in relation to our patients and the maladaptive defenses to which they cling – once necessary for them to survive but now interfering with their ability to thrive.
On the one hand, we have respect for our patients and for the choices, no matter how unhealthy, that they find themselves continuously making; on the other hand, we have a vision of who we think they could be were they but able/willing to make healthier choices for themselves. Indeed, we are always struggling to find an optimal balance within ourselves between accepting the reality of who our patients are and wanting them to change.
Whether we are working within the interpretive framework of classical psychoanalytic theory, the corrective-provision framework of self psychology, or the intersubjective framework of contemporary relational theory, we are therefore ever busy deciding – whether consciously or unconsciously – if we should “be with our patients where they are” (Akhtar’s homeostatic attunement) or “direct their attention to elsewhere” (Akhtar’s disruptive attunement) – a critically important balance that is needed if the analytic endeavor is to be advanced.
To demonstrate the translation of these theoretical constructs into clinical practice, I will be proposing a number of broadly applicable “template” interventions that juxtapose both the patient’s “defensive need” to maintain “same old same old” and the patient’s “adaptive capacity” to allow for “something new, different, and better.” Clinical vignettes will be offered that demonstrate judicious and ongoing use of these “optimally stressful” interventions that alternately support and challenge the defense, thereby galvanizing advancement of the patient, over time, from psychological rigidity to psychological flexibility.
If indeed the therapeutic goal is deep and sustained psychodynamic change, then it behooves all of us to become comfortable with the concept of provoking – with our interventions – enough incentivizing anxiety and destabilizing stress within our patients that there will be both impetus and opportunity for them, ultimately, to transform rigid defense into more flexible adaptation. The strategic formulation of interpretations specifically designed to generate this optimal stress is indeed both an art and a science.
This document provides a summary of a presentation by Dr. Bipin Jethani on revisiting Samuel Hahnemann through his works and principles. Some of the key points made in the presentation include: Hahnemann was ahead of his time in areas like psychosomatic medicine, public health, contagious disease, and experimental pharmacology. The presentation also discusses Hahnemann's appreciation of areas like surgery, allopathy in emergencies, and the material and dynamic components of the human body. Clinical cases are presented to illustrate Hahnemannian concepts and pearls of wisdom are shared from Hahnemann's writings.
Martha Stark MD – Oct 2019 – The Transformative Power of Optimal Stress – Pre...Martha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and inherent capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unmastered early-on relational traumas” replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
Martha Stark MD – 13 Apr 2023 – The Therapeutic Use of Optimal Stress to Prov...Martha Stark MD
The therapeutic provision of “optimal stress” – against the backdrop of an empathically attuned and authentically engaged therapy relationship – is sometimes the magic ingredient needed to overcome the inherent resistance to change so frequently encountered in patients with longstanding emotional injuries. Ongoing challenge will destabilize and support will then prompt restabilization at ever-higher levels of resilience and adaptive capacity.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
[KINDLE]⚡book✔ Infectious Behavior Brain-Immune Connections in Autism Schizo...nonvoluaswer
In Infectious Behavior neurobiologist Paul Patterson examines the involvement of the immune system in autism schizophrenia and major depressive disorder. Although genetic approaches to these diseases have garnered the lion's share of publicity and funding scientists are uncovering evidence of the important avenues of communication between the brain and the immune system and their involvement in mental illness. Patterson focuses on this brainimmune crosstalk exploring the possibility that it may help us understand the causes of these common but still mysterious diseases. The heart of this engaging book accessible to nonscientists concerns the involvement of the immune systems of the pregnant
This is a presentation made on stress and related problems related to physiological aspects of it. It also explains General Adaption Syndrome i.e our bodies response to stressor hormone like Oxytocin and cortisol in basic 3 stages, also some of the sympathetic and parasympathetic functions. It gives you general idea about the "Stress curve" .
This document summarizes a feasibility analysis for a proposed method to control diseases by manipulating the relationship between the immune and nervous systems using bioelectronic techniques. It first provides background on the costs of diseases related to immune response and the potential market opportunity. It then reviews the physiology of interactions between the central/peripheral nervous, endocrine and immune systems, focusing on the role of the vagus nerve in immunomodulation. Specifically, it discusses how vagus nerve stimulation has anti-inflammatory effects and been shown to ameliorate systemic inflammation in previous research. The document proposes developing a device to help gain more objective results from neuromodulation techniques for immune applications.
This document provides an overview of stress, including its definition, types, causes, biological mechanisms, effects, and management. It defines stress as the body's reaction to excessive demands or pressures, and notes there are three main types: acute, episodic, and chronic stress. The biological mechanisms of stress involve the hypothalamus-pituitary-adrenal axis activating a stress response through the release of cortisol and other hormones. Prolonged stress can negatively impact physical and mental health. Effective stress management includes identifying stressors, adapting coping strategies, and accepting what cannot be changed.
Stress is the body's response to any demand placed on it and can be caused by both external and internal factors. The body responds to stress through the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, which trigger the release of hormones like cortisol and neurotransmitters like epinephrine that prepare the body for the fight-or-flight response. While stress responses evolved to be helpful in the short term, prolonged stress over time can negatively impact health and increase risks of diseases and unhealthy behaviors. Managing stress through exercise, meditation, relaxation techniques, and maintaining social support networks can help mitigate stress's harmful effects.
Chronic diseases can be influenced by and influence chronic stress through complex relationships. The document discusses how stress may exacerbate chronic diseases like multiple sclerosis through effects on the immune system. It prompts the reader to reflect on a chronic disease and how it could impact or be impacted by stress, and to propose a behavioral intervention that may help treat the disease by addressing stress. The discussion suggests taking a holistic perspective to better understand and manage relationships between stress and chronic illness.
MIGRAINE A DEFICIENCY DISORDER OF NEUROCHEMICALSpharmaindexing
This document discusses migraine, a common type of headache. It provides background on the history of migraine and theories about its pathophysiology. Migraine is considered a neurovascular disorder involving activation of the trigeminal nerve and blood vessel dilation in the brain. It affects around 12% of the population and is more prevalent in females. The document reviews risk factors, symptoms, classification of migraine types, and potential mechanisms in the brain involved in aura and headache pain.
Immune Factors in Mental Diagnoses.docxstudywriters
The document discusses the theory that certain mental health diagnoses may be linked to dysfunctional immune cells. These diagnoses include Alzheimer's disease, autism, bipolar disorder, major depression, obsessive compulsive disorder, and schizophrenia. Research is still early but exploring these psychoneuroimmunology links. The implications could impact treatment approaches if more connections are found between mental health and immune system issues. The author is asked to select a mental health diagnosis other than depression, explain related immune theories and propose two cognitive/behavioral interventions that could help immune function for that diagnosis.
This document summarizes a research article that investigated whether disrupting the circadian rhythms of rats by exposing them to a 22-hour light-dark cycle leads to depressive-like behaviors. The study found that rats exposed to the disrupted light cycle showed signs of depression, including decreased pleasure-seeking behaviors, sexual dysfunction, and increased immobility in tests for depressive symptoms. Analysis also revealed changes in brain chemistry related to mood. The results support the hypothesis that misalignment of circadian rhythms due to problems with the brain's central clock may contribute to the development of depression.
This document discusses the potential shared pathophysiological mechanism of dysregulated inflammation linking neurocognitive and behavioral dysfunction in individuals with HIV, depression, and chronic stress. It provides background on psychoneuroimmunology and highlights classic studies showing interactions between behavior, the immune system, and nervous system. Emotions are discussed as being central to these interactions through their physiological effects in the brain and ability to aid memory formation and physiological regulation. Individual differences, genetics, and social contexts can impact these psychoneuroimmunological relationships.
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Martha Stark MD – Clinical Interventions – Chapter 2 of my WORKING WITH RESIS...Martha Stark MD
In order to demonstrate the ways in which the concepts of conflict and resistance can be applied to the clinical situation, let us think about the following three situations:
1. The patient is obviously upset but is trying hard not to cry.
2. The patient knows that her therapist will not laugh at her but finds herself fearing that the therapist might.
3. The patient is upset with her therapist and knows, on some level, that she must eventually confront the reality of just how disappointed she really is, but she would like to think that she could get better without having to do that.
In our interventions in these three situations of conflict, we have three options, and we must decide from moment to moment which to choose.
Martha Stark MD – Model 1 – The Interpretive Perspective of Classical Psychoa...Martha Stark MD
If deep and enduring psychodynamic change is the ultimate goal of treatment, then periodically juxtaposing seemingly contradictory “forces” (Hegel’s thesis and antithesis) will eventually jump-start the patient’s “adaptive recovery” by creating optimally stressful, growth-incentivizing “mismatch experiences.”
I will be proposing use of something to which I refer as a “conflict statement” – a clinically useful and almost universally applicable therapeutic intervention strategically designed to target internal conflictedness between anxiety-provoking (but ultimately growth-promoting) forces pressing “yes” and anxiety-relieving (but growth-impeding) resistant counterforces defending “no.”
The stress and strain of the “destabilizing dissonance” hereby created will provide the “therapeutic leverage” needed for the patient gradually, over time, to relinquish the tenacity of her rigid attachment to the defense in favor of a more flexible adaptation – a “compromise position” that will “reconcile their common truths” (Hegel’s synthesis) and transform conflict into collaboration.
The strategic construction of conflict statements requires of the therapist that she be able both to support the patient’s defense by “being with the patient where she is” and to challenge the patient’s defense by “directing the patient’s attention to where the therapist would want her to go.” I will be offering specific clinical examples to demonstrate the impact of these powerfully impactful psychotherapeutic interventions. No pain, no gain…
Martha Stark MD – 2019 A Heart Shattered, The Private Self, and A Life Unlive...Martha Stark MD
Patients who have never fully confronted – and grieved – the pain of their early-on heartbreak will often cling tenaciously to their hope that perhaps someday the object of their desire will be forthcoming. But there are others who, in the aftermath of their early-on heartbreak, will find themselves withdrawing completely from the world of objects – their heart shattered...
To protect themselves against being once again devastated, this latter group of patients will retreat, withdraw, detach themselves from relationships – psychic retreat, schizoid withdrawal, emotional detachment from the world of people, from life itself – only then to find themselves overwhelmed by intense feelings of isolation, alienation, and emptiness – the competent, accomplished, cheerful, compliant false (public) self they present to the world belying the truth that lies hidden within, namely, not only their private turmoil, tormented heartbreak, harrowing loneliness, and annihilating terror but also their stymied creativity and desperate (albeit conflicted) longing for meaningful connectedness with the world.
Instead of relentless hope, which figures prominently in my Model 2 (an absence of good model that focuses on the patient’s relentless pursuit of new good), and its cousin relentless outrage, which figures prominently in my Model 3 (a presence of bad model that focuses on the patient’s compulsive re-enactment of old bad in the face of frustrated desire), the experience of being-in-the-world for these latter (Model 4) patients will be one of relentless despair – a profound hopelessness that they keep hidden behind the false self they present to the world, a self-protective armor that masks the deeply entrenched brokenness and thwarted potential of the true self (Stark 2017).
Whereas the relentless hope of the Model 2 patient and the relentless outrage of the Model 3 patient speak to the patient’s intense (albeit maladaptive) engagement with the world of objects, the relentless despair of the Model 4 patient speaks to the patient’s utter lack of any real engagement with the world of objects.
Many a patient, as a child, has suffered great heartache at the hands of a misguided, even if well-intentioned, parent, be it in the form of psychological trauma and abuse (too much bad) or emotional deprivation and neglect (not enough good). Such a patient may never have had occasion to confront the pain of her grief about the parent's unwitting but devastating betrayal of her. Instead, she has defended herself against the pain of her heartache by pushing it, unprocessed, out of her awareness and clinging instead to the illusion of her parent (or a stand-in for her parent) as good and as ultimately forthcoming if she (the patient) could but get it right.
Under the sway of her repetition compulsion, the patient – as she struggles through her life – will find herself delivering into each new relationship her desperate hope that perhaps this time, were she to be but good enough, want it badly enough, or suffer deeply enough, she might yet be able to transform this new object of her relentless desire into the perfect parent she should have had as a child – but never did (Stark 1994a, 1994b, 1999, 2015).
As long as the patient continues her relentless pursuits, however, and refuses to come to terms with the reality of the limitations, separateness, and immutability of the people in her world – and the limits of her power to make them change – then she will be consigning herself to a lifetime of chronic frustration, heartache, and unremitting feelings of impotent rage and profound despair.
Elvin Semrad (Rako 1983) captures this poignantly with the following: “Pretending that <something> can be when it can’t is how people break their heart.”
Martha Stark MD – 2016 How Does Psychotherapy Work?.pdfMartha Stark MD
I have always found the following quote from Gary Schwartz’s 1999 The Living Energy Universe to be inspirational: “One of science’s greatest challenges is to discover certain principles that will explain, integrate, and predict large numbers of seemingly unrelated phenomena.” So too my goal has long been to be able to tease out overarching principles – themes, patterns, and repetitions – that that are relevant in the deep healing work that we do as psychotherapists.
Drawing upon concepts from fields as diverse as systems theory, chaos theory, quantum mechanics, solid-state physics, toxicology, and psychoanalysis to inform my understanding, on the pages that follow I will be offering what I hope will prove to be a clinically useful conceptual framework for understanding how it is that healing takes place – be it of the body or of the mind. More specifically, I will be speaking both to what exactly provides the therapeutic leverage for healing chronic dysfunction and to how we, as psychotherapists, can facilitate that process?
Just as with the body, where a condition might not heal until it is made acute, so too with the mind. In other words, whether we are dealing with body or mind, superimposing an acute injury on top of a chronic one is sometimes exactly what a person needs in order to trigger the healing process.
More specifically, the therapeutic provision of “optimal stress” – against the backdrop of empathic attunement and authentic engagement – is often the magic ingredient needed to overcome the inherent resistance to change so frequently encountered in our patients with longstanding emotional injuries and scars.
Too much challenge (traumatic stress) will overwhelm. Too little challenge (minimal stress) will serve simply to reinforce the dysfunctional status quo. But just the right combination of challenge and support (optimal stress) will “galvanize to action” and provoke healing. I refer to this as the Goldilocks Principle of Healing.
And so it is that with our finger ever on the pulse of the patient’s level of anxiety and capacity to tolerate further challenge, we formulate “incentivizing statements” strategically designed “to precipitate disruption in order to trigger repair.” Ongoing use of these optimally stressful interventions will induce healing cycles of defensive destabilization followed by adaptive restabilization at ever-higher levels of integration, dynamic balance, and functional capacity.
Behind this “no pain, no gain” approach is my firm belief in the
underlying resilience that patients will inevitably discover within themselves once forced to tap into their inborn ability to self-correct in the face of environmental challenge – an innate capacity that will enable them to advance, over time, from dysfunctional defensive reaction to more functional adaptive response.
Martha Stark MD – 2015 The Transformative Power of Optimal Stress.pdfMartha Stark MD
Freud’s interest was in the internal conflict that exists between, on the one hand, untamed id drives (most notably sexual and aggressive ones) clamoring for gratification and release and, on the other hand, the defenses mobilized by an undeveloped ego made anxious by the threatened breakthrough of those drives – conflict that will create neurotic suffering and interfere with the capacity to derive pleasure and fulfillment from love, work, and play (Freud 1926).
Using as a springboard Freud’s premises of drive-defense conflict as the source of a person’s difficulties in life and of the goal of treatment as therefore transformation of id energy into ego structure so that primitive defenses can be relinquished and conflict resolved – “Where id was, there shall ego be” (Freud 1923), I will go on to broaden Freud’s conceptualization of neurotic conflict to encompass, more generally, growth-impeding tension between anxiety-provoking but ultimately health-promoting internal forces pressing yes and anxiety- assuaging internal counterforces defending no.
The aim of treatment will then become (1) to tame the id so that its now more manageable energy can be redirected into more constructive channels and used to power the pursuit of healthier endeavors and (2) to strengthen the ego so that it will become both better able to cope with the multitude of anxiety-provoking stressors (internal and external) to which it is being continuously exposed and more skilled at harnessing id energy to fuel actualization of potential. In essence, a tamer id and a stronger ego will enable the patient to cope with the stress of life (Selye 1978) by adapting instead of defending – “Where defense was, there shall adaptation be.”
In the treatment situation, the therapist will offer psychotherapeutic interventions specifically designed to precipitate disruption in order to trigger repair (Stark 2008, 2012, 2014). To be effective against dysfunctional defenses that have become firmly entrenched over time, despite having long since outlived their usefulness, these therapeutic interventions must be optimally stressful. In other words, they must be strategically formulated to offer just the right combination of challenge and support.
Martha Stark MD – 1994 A Primer on Working with Resistance.pdfMartha Stark MD
Every day after work, a very depressed young man sits in the dark in his living room hour after hour, doing nothing, his mind blank. By his side is his stereo and a magnificent collection of his favorite classical music. The flick of a switch and he would feel better- and yet night after night, overwhelmed with despair, he just sits, never once touching that switch.
I would like to suggest that we think of this man as being in a state of internal conflict (although he may not, at this point, be aware of such conflict). He could turn on his stereo, but he does not. He could do something that would make him feel better, but he does nothing. Within this man is tension between what he "should" let himself do and what he finds himself doing instead.
In general, patients both do and don't want to get better. They both do and don't want to maintain things as they are. They both do and don't want to get on with their lives. They both are and aren't invested in their suffering. They are truly conflicted about all the choices that confront them.
The patient may protest that he desperately wants to change. He does and he doesn't. He may insist that he would do anything in order to feel better. Well, yes and no. On some level, everybody wants things to be better, but few are willing to change.
Drive theory conceives of conflict as involving internal tension between id impulse insisting "yes" and ego defense protesting "no" (with the superego coming down usually on the side of the ego). In Ralph Greenson's (1967) words: "A neurotic conflict is an uncon- scious conflict between an id impulse seeking discharge and an ego defense warding off the impulse's direct discharge or access to consciousness" (p. 17).
Although drives are considered part of the id, affects (drive derivatives) are thought to reside in the ego; in fact, the ego is said to be the seat of all affects. When Freud writes of psychic conflict between the id and the ego, it is understood that sometimes he is referring to conflict between an id drive and an ego defense and sometimes he is referring to conflict between an anxiety-provoking affect (in the ego but deriving from the id) and an ego defense.
Martha Stark MD – 1994 Working with Resistance.pdfMartha Stark MD
This book is about the patient’s resistance and his refusal to grieve. Drawing upon concepts from classical psychoanalysis, object relations theory, and self psychology, I present a model of the mind that takes into consideration the relationship between unmourned losses and how such losses are internally recorded – as both absence of good (structural deficit) and presence of bad (structural conflict). These internal records of traumatic disappointments sustained early on give rise to forces that interfere with the patient’s movement toward health – forces that constitute, therefore, the resistance.
Within the patient is a tension between that which the patient should let himself do/feel and that which he does/feels instead. Patient and therapist, as part of their work, will need to be able to understand and name, in a profoundly respectful fashion, both sets of forces –both those healthy ones, which impel the patient in the direction of progress, and those unhealthy resistive ones, which impede such progress. As part of the work to be done, the patient must eventually come to appreciate his investment in his defenses, how they serve him, and the price he pays for holding on to them.
My interest is in the interface between theory and practice –the ways in which theoretical constructs can be translated into the clinical situation; to that end, I suggest specific, prototypical interventions for each step of the working-through process.
My contention is that the resistant patient is, ultimately, someone who has not yet grieved, has not yet confronted certain intolerably painful realities about his past and present objects. Instead, he protects himself from the pain of knowing the truth about his objects by clinging to misperceptions of them; holding on to his defensive need not to know enables him not to feel his grief.
To the extent that the patient is defended, to that extent will he be resistant to doing the work that needs ultimately to be done – grief work that will enable him to let go of the past, let go of his relentless pursuit of infantile gratification, and let go of his compulsive repetitions. Only as the patient grieves, doing now what he could not possibly do as a child, will he get better.
I believe that mental health has to do with the capacity to experience one’s objects as they are, uncontaminated by the need for them to be otherwise. A goal of treatment, therefore, is to transform the patient’s need for his objects to be other than who they are into the capacity to accept them as they are.
Martha Stark MD – 28 Oct 2017 – Relentless Despair – Model 4.pptxMartha Stark MD
An anonymous quote but very to the point is the following:
I gave you a part of me that I knew you could break – but you didn’t.
Patients who have never fully confronted – and grieved – the pain of their early-on heartbreak will often cling tenaciously to their hope that perhaps someday the “object of their desire” will be forthcoming. But there are others who, in the aftermath of their early-on heartbreak, will find themselves withdrawing completely from the “world of objects” – their heart shattered…
To protect themselves from being once again devastated, these latter patients retreat, withdraw, detach themselves from relationships, from the world – psychic retreat, schizoid withdrawal, emotional detachment from life itself – only then to find themselves overwhelmed by intense feelings of isolation, alienation, and emptiness – the competent, accomplished, cheerful, compliant “false (public) self” that they present to the world belying the truth of what lies hidden, namely, their private turmoil, tormented heartbreak, harrowing loneliness, and annihilating terror as well as their stymied creativity and desperate (albeit conflicted) longing for meaningful connectedness with the world.
Instead of “relentless hope” (which figures prominently in my Model 2, with its focus on the patient’s “relentless pursuits”) and, when thwarted, “relentless outrage” (which figures prominently in my Model 3, with its focus on the patient’s “compulsive repetitions”), the experience-of-being-in-the-world for these latter (Model 4) patients will be one of “relentless despair” – a “profound hopelessness” that they keep masked by a self-protective “false self” armor that obscures their underlying brokenness and the “thwarted potential” of their “true self.”
Whereas the relentless hope of the Model 2 patient and the relentless outrage of the Model 3 patient speak to the patient’s intense – albeit maladaptive – engagement with the world of objects, the relentless despair of the Model 4 patient speaks to the patient’s complete lack of any real engagement with the world of objects.
Martha Stark MD – Comprehensive Overview of the 4 Models – A Potpourri of Sli...Martha Stark MD
Dr. Martha Stark has developed a comprehensive theory of therapeutic action that integrates the interpretive perspective of classical psychoanalysis (which speaks to the power of insight); the corrective-provision perspective of self psychology and other deficit theories (which speaks to the importance of corrective experience as compensation for early-on deficiencies); and the contemporary relational perspective (which speaks to mutual enactment and negotiation by both patient and therapist of the entanglements that will inevitably emerge at the intimate edge of their authentic engagement).
Her focus throughout the seminar will be on the interface between theory and practice; and Dr. Stark will demonstrate, by way of numerous clinical vignettes and prototypical interventions, the ways in which the three modes of therapeutic action (knowledge, experience, and relationship) can be used to accelerate the healing process.
review of basic constructs: knowledge, experience, relationship as curative factors; “supporting” by being with the patient where she is vs. “challenging” by directing her attention to elsewhere; the therapeutic process as involving recursive cycles of defensive collapse and adaptive reconstitution at ever higher levels of integration and balance.
the process of transforming defense into adaptation; the importance of awareness (wisdom), acceptance, and accountability; therapist as neutral object, empathic selfobject, authentic subject; prototypical interventions specifically designed to facilitate the grieving process and to accelerate the healing.
working through the negative transference and disruptions to the positive transference; transforming infantile need into mature adult capacity; focusing on the contributions of both patient and therapist to the relational dynamics at their intimate edge; use of instructor’s process recordings to demonstrate the role of knowledge, experience, and relationship in strengthening the ego, consolidating the self, and resolving relational difficulties.
Martha Stark MD – 26 - 27 Apr 2019 – My Psychodynamic Synergy Paradigm – A C....Martha Stark MD
Dr. Martha Stark has developed a comprehensive theory of therapeutic action that integrates the interpretive perspective of classical psychoanalysis (which speaks to the power of insight); the corrective-provision perspective of self psychology and other deficit theories (which speaks to the importance of corrective experience as compensation for early-on deficiencies); and the contemporary relational perspective (which speaks to mutual enactment and negotiation by both patient and therapist of the entanglements that will inevitably emerge at the intimate edge of their authentic engagement).
Her focus throughout the seminar will be on the interface between theory and practice; and Dr. Stark will demonstrate, by way of numerous clinical vignettes and prototypical interventions, the ways in which the three modes of therapeutic action (knowledge, experience, and relationship) can be used to accelerate the healing process.
review of basic constructs: knowledge, experience, relationship as curative factors; “supporting” by being with the patient where she is vs. “challenging” by directing her attention to elsewhere; the therapeutic process as involving recursive cycles of defensive collapse and adaptive reconstitution at ever higher levels of integration and balance.
the process of transforming defense into adaptation; the importance of awareness (wisdom), acceptance, and accountability; therapist as neutral object, empathic selfobject, authentic subject; prototypical interventions specifically designed to facilitate the grieving process and to accelerate the healing.
working through the negative transference and disruptions to the positive transference; transforming infantile need into mature adult capacity; focusing on the contributions of both patient and therapist to the relational dynamics at their intimate edge; use of instructor’s process recordings to demonstrate the role of knowledge, experience, and relationship in strengthening the ego, consolidating the self, and resolving relational difficulties.
Martha Stark MD – 20 Oct 2021 – Relentless Hope – The Refusal to Grieve.pptxMartha Stark MD
Relentless hope is a defense to which the patient clings in order not to have to feel the pain of her disappointment in the object, the hope a defense ultimately against grieving. The patient’s refusal to deal with the pain of her grief about the object (be it the infantile, a contemporary, or the transference object) fuels the relentlessness with which she pursues it, both the relentlessness of her hope that she might yet be able to make the object over into what she would want it to be and the relentlessness of her outrage in those moments of dawning recognition that, despite her best efforts and most fervent desire, she might never be able to make that actually happen. It will be suggested that maturity involves transforming this infantile need to have one’s objects be other than who they are into the healthy capacity to accept them as they are.
Drawing upon four modes of therapeutic action (enhancement of knowledge "within," provision of experience "for," engagement in relationship "with," and facilitation of flow "throughout"), Martha will offer a number of prototypical interventions specifically designed to facilitate transformation of the patient’s “defensive” need to possess and control the object (and, when thwarted, to punish the object by attempting to destroy it) into the “adaptive” capacity to relent, grieve, accept, forgive, internalize, separate, let go, and move on. Martha will also offer a number of clinical vignettes that speak to the power of an integrative approach that focuses on accountability and development of the capacity to relent (on the parts of both patient and therapist), the ultimate goal being to transform defensive need into adaptive capacity – the defensive need to re-enact old dramas again and again into the adaptive capacity to do it differently this time…
Martha Stark MD – 10 Sep 2012 – Relentless Hope – The Refusal to Grieve.pptxMartha Stark MD
Relentless hope is a defense to which the patient clings in order not to have to feel the pain of her disappointment in the object, the hope a defense ultimately against grieving. The patient’s refusal to deal with the pain of her grief about the object (be it the infantile, a contemporary, or the transference object) fuels the relentlessness with which she pursues it, both the relentlessness of her hope that she might yet be able to make the object over into what she would want it to be and the relentlessness of her outrage in those moments of dawning recognition that, despite her best efforts and most fervent desire, she might never be able to make that actually happen. It will be suggested that maturity involves transforming this infantile need to have one’s objects be other than who they are into the healthy capacity to accept them as they are.
Drawing upon four modes of therapeutic action (enhancement of knowledge "within," provision of experience "for," engagement in relationship "with," and facilitation of flow "throughout"), Martha will offer a number of prototypical interventions specifically designed to facilitate transformation of the patient’s “defensive” need to possess and control the object (and, when thwarted, to punish the object by attempting to destroy it) into the “adaptive” capacity to relent, grieve, accept, forgive, internalize, separate, let go, and move on. Martha will also offer a number of clinical vignettes that speak to the power of an integrative approach that focuses on accountability and development of the capacity to relent (on the parts of both patient and therapist), the ultimate goal being to transform defensive need into adaptive capacity – the defensive need to re-enact old dramas again and again into the adaptive capacity to do it differently this time…
Martha Stark MD – 5 Jun 2021 – A Heart Shattered and Relentless Despair.pptxMartha Stark MD
This document provides an overview of a seminar on an existential-humanistic approach to healing brokenness and easing despair in patients. The seminar will focus on Model 4 patients who have experienced early heartbreak and withdrawal from relationships due to a "shattered heart". It will discuss helping patients overcome dread of emotional surrender and providing an opportunity to "regress in order to redo" early experiences. The presenter's psychodynamic synergy paradigm incorporates five therapeutic models, including one focused on patients experiencing relentless despair and nonrelatedness due to early relational failures.
Martha Stark MD – 26 Jun 2009 – The Overwhelmed Heart.pptxMartha Stark MD
This document discusses coronary artery disease and the impact of stress on heart health. It notes that coronary artery disease often develops silently and can cause sudden death in some cases. Chronic stress can damage blood vessels and cause plaque buildup over time by increasing blood pressure and viscosity. Psychological stress, depression, obesity, and other risk factors place cumulative stress on the heart and compromise its ability to adapt. Maintaining the heart's resilience by reducing stressors and replenishing nutrients is important for cardiovascular health.
Martha Stark MD – 21 Feb 2009 – The Wisdom of the Matrix – From Chaos to Cohe...Martha Stark MD
The document discusses how coherence emerges from chaos in complex adaptive systems like living organisms. It argues that through ongoing cycles of disruption and repair, such systems can self-organize and evolve from disorder to higher levels of order and coherence in response to environmental inputs. The ability of a system to process and integrate stressors over time determines whether it progresses towards health or disease.
Martha Stark MD – 26 Jun 2009 – Murmur of the Heart.pptxMartha Stark MD
traumatic stress – stress that the system cannot process and must therefore defend against
optimal stress – stress that the system can process, integrate, and ultimately adapt to, although always at some cost to the system
it's how well the living system (the MindBodyMatrix) is able to manage the cumulative impact of the myriad environmental stressors to which it is being continuously exposed that will make of them either traumatic events or growth opportunities
and that ability to manage stress is a story about the system's ability to process, integrate, and adapt to the impact of environmental challenge, input from the outside that either threatens to overwhelm the system or prompts the system to mobilize its ability to heal itself
Martha Stark MD – 4 Jun 2010 – EMFs and the Excitotoxic Cascade.pptxMartha Stark MD
Unexplained Chronic Illness
Martin Pall's compelling conceptualization of the excitotoxic cascade and its pivotal role in both the initiation and the perpetuation of chronic multisystem illnesses
one or more short-term stressors
chemical sensitivity – pesticides and organic solvents
chronic fatigue – bacterial and viral infections
fibromyalgia – physical traumas
PTSD – severe psychological traumas
to which the body responds with an outpouring of
excitotoxins (glutamate)
inflammatory factors (cytokines and eicosanoids)
free radicals (nitric oxide)
stress-induced outpouring of endogenous excitotoxins, inflammatory cytokines, and free radicals sets in motion (in certain susceptible individuals) the nitric oxide / peroxynitrite cycle
a viciously destructive, self-propagating cycle involving
immune stimulation, inflammatory cytokines, membrane destabilization, synaptic overactivity, opening of calcium-permeable channels, massive calcium influx, etc.
and culminating in chronic illness
Martha Stark MD – 22 Jun 2018 – A Heart Shattered, Relentless Despair, and A ...Martha Stark MD
An anonymous quote but very to the point is the following:
I gave you a part of me that I knew you could break – but you didn’t.
Patients who have never fully confronted – and grieved – the pain of their early-on heartbreak will often cling tenaciously to their hope that perhaps someday the “object of their desire” will be forthcoming. But there are others who, in the aftermath of their early-on heartbreak, will find themselves withdrawing completely from the “world of objects” – their heart shattered…
To protect themselves from being once again devastated, these latter patients retreat, withdraw, detach themselves from relationships, from the world – psychic retreat, schizoid withdrawal, emotional detachment from life itself – only then to find themselves overwhelmed by intense feelings of isolation, alienation, and emptiness – the competent, accomplished, cheerful, compliant “false (public) self” that they present to the world belying the truth of what lies hidden, namely, their private turmoil, tormented heartbreak, harrowing loneliness, and annihilating terror as well as their stymied creativity and desperate (albeit conflicted) longing for meaningful connectedness with the world.
Instead of “relentless hope” (which figures prominently in my Model 2, with its focus on the patient’s “relentless pursuits”) and, when thwarted, “relentless outrage” (which figures prominently in my Model 3, with its focus on the patient’s “compulsive repetitions”), the experience-of-being-in-the-world for these latter (Model 4) patients will be one of “relentless despair” – a “profound hopelessness” that they keep masked by a self-protective “false self” armor that obscures their underlying brokenness and the “thwarted potential” of their “true self.”
Whereas the relentless hope of the Model 2 patient and the relentless outrage of the Model 3 patient speak to the patient’s intense – albeit maladaptive – engagement with the world of objects, the relentless despair of the Model 4 patient speaks to the patient’s complete lack of any real engagement with the world of objects.
Martha Stark MD – 30 Sep 2018 – The Transformative Power of Optimal Stress.pptxMartha Stark MD
Psychodynamic psychotherapy affords the patient an opportunity – albeit a belated one – to master experiences that had once been overwhelming, and therefore defended against, but that can now, with enough support from the therapist and by tapping into the patient's underlying resilience and capacity to cope with stress, be processed, integrated, and ultimately adapted to. This opportunity for belated mastery of traumatic experiences and transformation of defense into adaptation speaks to the power of the transference, whereby the here-and-now is imbued with the primal significance of the there-and-then.
Ultimately, the therapeutic goal is to transform less-evolved defense into more-evolved adaptation – from externalizing blame to taking ownership, from whining and complaining to becoming proactive, from dissociating to becoming more present, from feeling victimized to becoming empowered, from being jammed up to harnessing one's energies and then channeling them into the pursuit of one's dreams, from denial to confronting head-on, from being critical to becoming more compassionate, and from cursing the darkness to lighting a candle.
Growing up (the task of the child) and getting better (the task of the patient) are therefore a story about transforming need into capacity – the need for immediate gratification into the capacity to tolerate delay, the need for perfection into the capacity to tolerate imperfection, the need for external regulation of the self into the capacity to be internally self-regulating, and the need to hold on into the capacity to let go.
In sum, it could be said that, as a result of intensive psychodynamic psychotherapy, "resistance" will be replaced by "awareness" and "actualization of potential," "relentless pursuit of the unattainable" replaced by "acceptance," "re-enactment of unresolved childhood dramas" replaced by "accountability," "retreat and resignation" replaced by "accessibility," and “relentless despair” replaced by “awakened hope.”
The focus throughout will be on the interface between theory and clinical practice.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...Donc Test
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Study Guide Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Course Hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Answers Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Course hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Study Guide Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Ebook Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Questions Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Stuvia
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Martha Stark MD – 22 Sep 2017 – Neuroinflammation and Depression – When the Domain of the Pain is the Brain.pptx
1. INFLAMMATION
AND DEPRESSION:
WHEN THE DOMAIN OF PAIN IS THE BRAIN
MARTHA STARK, MD
Faculty, Harvard Medical School
MarthaStarkMD @ HMS.Harvard.edu
Friday, September 22, 2017
1
2. GOALS AND OBJECTIVES
PROVIDE AN EXPLANATION AS TO WHY
ACUTE STRESS CAN “OPTIMIZE” BUT
CHRONIC STRESS WILL “TRAUMATIZE”
EXPLAIN THE CONCEPT OF LIMBIC KINDLING
AND ITS RELEVANCE TO DEPRESSION
ELABORATE UPON THE RELATIONSHIP BETWEEN
STRESS – INDUCED NEUROENDOCRINE AND
STRESS – INDUCED NEUROIMMUNE DYSREGULATION
ON THE ONE HAND AND DEPRESSION ON THE OTHER
SPEAK TO THE RELATIONSHIP BETWEEN
CHRONICALLY ELEVATED ANTI – INFLAMMATORY
CORTISOL AND CHRONICALLY ELEVATED
PRO – INFLAMMATORY CYTOKINE LEVELS ON THE ONE
HAND AND CHRONIC INFLAMMATION ON THE OTHER
2
3. PREVIEW
THE STRESS RESPONSE ~ GENERAL ADAPTATION SYNDROME
ACUTE AND CHRONIC STRESS ~ BIPHASIC DOSE – RESPONSE
WALTER B CANNON ~ HANS SELYE
UPSTREAM APPROACH ~ FERRETING OUT UNDERLYING CAUSES
ANTECEDENT PRIMING (“SENSITIZING”) FACTORS
LIMBIC KINDLING ~ HYPERSENSITIVITY TO STRESS
REVERSIBLE EPIGENETIC MODIFICATIONS
LIFESTYLE CHOICES ~ ENVIRONMENTAL EXPOSURES
HOMEOSTASIS ~ ALLOSTASIS
THE GROUND REGULATION SYSTEM ~ THE WISDOM OF THE BODY
REGULATORY CAPACITY ~ DYSREGULATION
ACTIVATED NEUROENDOCRINE SYSTEM
UPREGULATED HYPOTHALAMIC – PITUITARY – ADRENAL “STRESS” AXIS
ANTI – INFLAMMATORY CORTISOL
DESENSITIZED CORTISOL RECEPTORS
ACTIVATED NEUROIMMUNE SYSTEM
UPREGULATED MACROPHAGES (IN THE BODY) AND MICROGLIA (IN THE BRAIN)
PRO – INFLAMMATORY CYTOKINES
INFLAMMATION IN BODY AND BRAIN ~ DEPRESSION
INFLAMMATORY BIOMARKERS
NATURAL (NEUROPROTECTIVE) ANTI – INFLAMMATORIES
3
5. “MELANCHOLIA BEHAVES
LIKE AN OPEN WOUND”
MOURNING AND MELANCHOLIA (FREUD 1917)
COMPLEX INTERCONNECTEDNESS BETWEEN
A DYSREGULATED STATE OF MIND
AND A DYSREGULATED IMMUNE SYSTEM
INDEED
WHETHER AS CAUSE, CORRELATE, OR CONSEQUENCE
CHRONIC INFLAMMATION IS IMPLICATED
IN DEPRESSION ABOUT ONE THIRD OF THE TIME
SO ALWAYS AT LEAST CONSIDER
NATURAL ANTI – INFLAMMATORIES
FOR YOUR DEPRESSED PATIENTS
5
6. 6
… epidemiological and clinical studies show a role for
inflammation as a risk factor for major depression …
(Muller 2014)
7. 7
… accumulating evidence suggests that immune
dysregulation plays an important role in the
pathophysiology of depression …
(Su 2015)
8. 8
… increased levels of circulating
pro-inflammatory cytokines and concomitant
activation of brain-resident microglia
can lead to depressive symptoms …
(Wohleb et al. 2016)
9. “DEPRESSION: AN INFLAMMATORY ILLNESS?”
(KRISHNADAS AND CAVANAGH 2012)
“FINDINGS FROM PRECLINICAL AND CLINICAL
STUDIES SUGGEST THAT DEPRESSION IS
ASSOCIATED WITH INFLAMMATORY PROCESSES”
AS EVIDENCE, THEY CITE THREE OBSERVATIONS:
ONE THIRD OF THOSE WITH DEPRESSION SHOW
ELEVATED PERIPHERAL INFLAMMATORY BIOMARKERS,
EVEN IN THE ABSENCE OF A MEDICAL ILLNESS
INFLAMMATORY ILLNESSES ARE ASSOCIATED
WITH GREATER RATES OF DEPRESSION
PATIENTS TREATED WITH CYTOKINES ARE AT
GREATER RISK FOR DEVELOPING DEPRESSION
AND THEY CONCLUDE ...
9
10. 10
… while it is unlikely that depression is a primary
inflammatory disorder, there is now evidence to
suggest that inflammation may play a subtle role
in the pathophysiology of depression …
(Krishnadas and Cavanagh 2012)
11. 11
… a link between chronic inflammation and
dementia, at least in some patients with
recurrent and chronic depression …
(Leonard 2017)
12. THE CHRONIC LOW – GRADE INFLAMMATION
ASSOCIATED WITH CHRONIC DEPRESSION
IS NOW THOUGHT TO BE A PREDISPOSING FACTOR
FOR DEMENTIA IN LATER LIFE
IN PART BECAUSE OF IMMUNE – MEDIATED ACCELERATED DEGRADATION
OF TRYPTOPHAN BY AN UPREGULATED KYNURENINE PATHWAY
MORE SPECIFICALLY
STRESS – INDUCED PRO – INFLAMMATORY CYTOKINES ACTIVATE THE
TRYPTOPHAN – DEGRADING ENZYME INDOLEAMINE 2,3 – DIOXYGENASE (IDO)
WHICH SHUNTS TRYPTOPHAN DOWN THE KYNURENINE PATHWAY
SUCH THAT LESS TRYPTOPHAN IS THEN AVAILABLE TO BE
SHUNTED DOWN THE PATHWAY THAT SYNTHESIZES SEROTONIN
(THE “HAPPY” NEUROTRANSMITTER / HORMONE IN THE BODY)
THE NET RESULT OF WHICH WILL BE NOT ONLY
DECREASED PRODUCTION OF SEROTONIN FROM TRYPTOPHAN
BUT ALSO
INCREASED PRODUCTION OF NEUROTOXIC EXCITOTOXINS
FROM KYNURENINE
LIKE QUINOLINIC ACID – A POTENT NMDA (GLUTAMATE) RECEPTOR AGONIST
12
13. 13
indoleamine
2,3-dioxygenase (IDO) (5-HTP)
5-hydroxytryptamine
(5-HT)
N-methyl-D-aspartate
(glutamate) receptor
neurotoxic
(NMDA receptor agonist)
neurotoxic
(causes oxidative stress)
STRESS-INDUCED
NEUROINFLAMMATION
UPREGULATES THE
KYNURENINE PATHWAY
activated
pro-inflammatory
cytokines
NET RESULT OF THE DYSREGULATED KYNURENINE PATHWAY
EXCITOTOXICITY AND COGNITIVE IMPAIRMENT
(R Dantzer et al. 2008)
the most potent
one of which is
interferon gamma
14. CHRONIC DEPRESSION
AND CHRONIC NEUROINFLAMMATION
DYSREGULATED
KYNURENINE PATHWAY
A NEUROTOXIC SHIFT IN THE BALANCE
OF KYNURENINE METABOLITES
EXCITOTOXICITY
PROGRESSIVE
NEURODEGENERATION
DEMENTIA
14
15. BUT CHICKEN OR EGG?
DOES INFLAMMATION CAUSE DEPRESSION?
OR
DOES DEPRESSION CAUSE INFLAMMATION?
15
16. FIRST A DISCLAIMER
SURGEONS KNOW NOTHING
BUT DO EVERYTHING
NEUROLOGISTS KNOW EVERYTHING
BUT DO NOTHING
PSYCHIATRISTS KNOW NOTHING
AND DO NOTHING
PATHOLOGISTS KNOW EVERYTHING
AND DO EVERYTHING
BUT TOO LATE
16
17. WELL, I AM A PSYCHIATRIST
IT HAS BEEN WRYLY SUGGESTED THAT PSYCHIATRY
WAS ONCE ALL ABOUT THE MIND
AND NOT AT ALL ABOUT THE BRAIN
BUT THAT PSYCHIATRY IS NOW ALL ABOUT THE BRAIN
AND NOT AT ALL ABOUT THE MIND
OUT OF RESPECT FOR THE INTIMATE INTERDEPENDENCE
OF MIND AND BRAIN AND IN DEFERENCE TO BOTH
MY PSYCHIATRIC AND MY NEUROSCIENCE COLLEAGUES,
I REFER TO THE “MENTAL COMPONENT” AS THE MindBrain
MY FAVORITE DESCRIPTION
OF PSYCHIATRY IS
“MEDICAL TREATMENT OF THE SOUL”
PARENTHETICALLY, A DISTINCTION SOMETIMES MADE
BETWEEN THE MIND AND THE BRAIN IS THAT
THE MIND INTERPRETS WHAT THE BRAIN PERCEIVES
17
18. THE VILLAINESS IN WHAT FOLLOWS WILL BE
DYSREGULATING STRESS
HERE DEFINED AS
ANYTHING THAT DISRUPTS HOMEOSTASIS
THE HEROINE WILL BE
RESTORATION OF HOMEOSTASIS
BY “LIGHTENING THE LOAD”
TO CORRECT FOR TOXICITIES
AND “REPLENISHING THE RESERVES”
TO CORRECT FOR DEFICIENCIES
ALL WITH AN EYE
TO “FACILITATING THE FLOW”
OF INFORMATION AND ENERGY
THROUGHOUT BODY AND BRAIN
SUCH THAT ENVIRONMENTAL STRESSORS CAN BE MORE
EFFECTIVELY PROCESSED, INTEGRATED, AND ADAPTED TO
AND HOMEOSTATIC BALANCE RESTORED
BY A NOW MORE RESILIENT SYSTEM 18
19. 19
“EVERY STRESS LEAVES
AN INDELIBLE SCAR,
AND THE ORGANISM
PAYS FOR ITS SURVIVAL
AFTER A STRESSFUL
SITUATION BY BECOMING
A LITTLE OLDER.”
HANS SELYE
20. “STRESS IS WHEN YOU
WAKE UP SCREAMING,
ONLY TO REALIZE
THAT YOU HAVEN’T
YET FALLEN ASLEEP”
ANONYMOUS
20
21. THE SPECIFIC REGULATORY ORGAN
SYSTEM(S) TARGETED BY STRESS
WILL BE THE RESULT OF
A “PROPRIETARY” COMBINATION OF
CONSTITUTIONAL ENDOWMENT
BIOCHEMICAL INDIVIDUALITY (WILLIAMS 1956)
LIFESTYLE AND ENVIRONMENTAL FACTORS
PSYCHOLOGICAL UNIQUENESS
ALTHOUGH AT LEAST ON SOME LEVEL
ALL THE BODY’S REGULATORY
SYSTEMS WILL BE IMPACTED,
THE STRESS – INDUCED DYSREGULATION
USUALLY MANIFESTS PRIMARILY IN
ONE OR TWO ORGAN SYSTEMS
21
22. SOMETIMES THE TARGET ORGAN WILL BE
THE CARDIOVASCULAR SYSTEM
(PERHAPS MANIFESTING AS HYPERTENSION)
SOMETIMES THE GASTROINTESTINAL SYSTEM
AND THE ORAL / GUT MICROBIOTA
(PERHAPS MANIFESTING AS GUM DISEASE
AND / OR INFLAMMATORY BOWEL DISEASE)
SOMETIMES THE MUSCULOSKELETAL SYSTEM
(PERHAPS MANIFESTING AS RHEUMATOID ARTHRITIS)
BUT
SOMETIMES THE TARGET ORGAN WILL BE
THE MindBrain
(PERHAPS MANIFESTING AS DEPRESSION)
22
23. WHEN THE TARGET ORGAN
IS THE MindBrain AND
MANIFESTS AS DEPRESSION,
THERE WILL USUALLY HAVE BEEN
ANTECEDENT PRIMING FACTORS
EARLY LIFE ADVERSITIES
DURING CRITICAL DEVELOPMENTAL PERIODS
GENETIC PREDISPOSITION
CAUSED BY MUTATIONS ~ POLYMORPHISMS
EPIGENETIC MODIFICATIONS
CAUSED BY LIFESTYLE CHOICES ~ ENVIRONMENTAL EXPOSURES
PSYCHOSOCIAL STRESSORS
RESULTING FROM
SOCIAL REJECTION ~ BULLYING ~ JOB STRESS ~ SOCIAL ISOLATION
23
24. AS IF BY “SCULPTING” SPECIFIC PATHWAYS IN THE BRAIN,
THESE FIRST – ORDER STRESSORS WILL
CREATE A LATENT VULNERABILITY
TO THE DEVELOPMENT OF
PSYCHOLOGICAL DIFFICULTIES
DYSREGULATED MENTAL STATES
WHEN LATER TRIGGERED BY
SECOND – ORDER STRESSORS
PSYCHOLOGICAL ~ PHYSIOLOGICAL ~ ENERGETIC
IN OTHER WORDS
THE GROUNDWORK IS BEING LAID
BY THESE SENSITIZING FACTORS FOR
SUBSEQUENT DEVELOPMENT OF
HYPERSENSITIVITY TO STRESS
24
25. THE LIMBIC SYSTEM IN THE BRAIN
MEDIATES THE STRESS RESPONSE
AND, WITH SUSTAINED STRESS, THE RESULT WILL BE
LIMBIC KINDLING
“THE MOST EXCITING CONCEPT IN NEUROSCIENCE
THAT MOST PEOPLE HAVE NEVER HEARD OF”
(GRATRIX 2014)
A FORM OF CLASSICAL (PAVLOVIAN) CONDITIONING
WHEREBY REPEATED EXPOSURES, OVER TIME,
TO A STRESSOR WILL SENSITIZE THE BRAIN
SUCH THAT EVENTUALLY EVEN MILD
STRESSORS WILL PROVOKE REACTIVITY
IN ESSENCE
LIMBIC KINDLING HARDWIRES THE
BRAIN FOR HYPERSENSITIVITY TO
STRESS AND CHRONIC ILLNESS
25
27. 27
… the limbic system (the “feeling and reacting” brain)
is positioned between the cortex (the “thinking” brain)
and the reptilian brain (the “old” brain connecting
the nervous system to the rest of the body) …
… the limbic system deals
with emotions, arousal,
and memory …
28. LIMBIC STRUCTURES INCLUDE
THE AMYGDALAE (THERE ARE ACTUALLY TWO OF THEM)
WHICH SOUND THE ALERT WHEN TRIGGERED
(WHETHER FROM “ABOVE” OR “BELOW”)
THE HYPOTHALAMUS
WHICH THEN INITIATES THE STRESS RESPONSE
LEADING TO STRESS – INDUCED ACTIVATION OF NOT ONLY
THE SYMPATHETIC NERVOUS SYSTEM BUT ALSO
THE NEUROENDOCRINE SYSTEM
PROMPTING THE RELEASE OF CORTISOL
FROM AN UPREGULATED
HYPOTHALAMIC – PITUITARY – ADRENAL (HPA) “STRESS” AXIS
AND
THE NEUROIMMUNE SYSTEM
PROMPTING THE RELEASE OF PRO – INFLAMMATORY CYTOKINES
FROM UPREGULATED PERIPHERAL MACROPHAGES (IN THE BODY)
AND UPREGULATED CENTRAL MICROGLIA (IN THE BRAIN) 28
29. AND, AGAIN, WHEN THE BRAIN
(FOR WHATEVER COMPLEX MIX OF PROPRIETARY REASONS)
IS THE PRIMARY SYSTEM AFFECTED BY THE STRESS,
THE NET RESULT WILL BE
NEUROINFLAMMATION AND
A DYSREGULATED STATE OF MIND
BUT NOW WE ENCOUNTER AN INTRIGUING PARADOX
ON THE ONE HAND
STRESS ACTIVATES THE HPA AXIS,
RESULTING IN THE RELEASE OF CORTISOL,
WHICH IS AN ANTI – INFLAMMATORY HORMONE
ON THE OTHER HAND
STRESS ACTIVATES THE IMMUNE SYSTEM,
RESULTING IN THE RELEASE OF
PRO – INFLAMMATORY CYTOKINES
HOW DO WE RECONCILE THESE OPPOSING
STRESS – INDUCED “INFLAMMATORY” REACTIONS?
29
30. LATER I WILL SHARE WITH YOU THE EXPLANATION
THAT RESEARCHERS HAVE OFFERED
IN AN EFFORT TO RESOLVE THIS CONUNDRUM
BUT, FOR NOW, SUFFICE IT TO SAY THAT
RESEARCHERS HAVE INDEED FOUND
A DIRECT LINK BETWEEN CHRONIC STRESS,
INCREASED LEVELS OF ANTI – INFLAMMATORY CORTISOL,
INCREASED LEVELS OF PRO – INFLAMMATORY CYTOKINES,
AND CHRONIC INFLAMMATION
AND THAT
THOSE PATIENTS WHO HAVE DEVELOPED
HYPERSENSITIVITY TO STRESS
BY VIRTUE OF EARLY LIFE ADVERSITIES
AND OTHER SENSITIZING STRESSORS
AND FOR WHOM THEIR MindBrain
IS THE PRIMARY TARGET ORGAN
WILL BE AT PARTICULAR RISK FOR THE DEVELOPMENT OF
DEPRESSION 30
31. BIOMARKERS OF SYSTEMIC INFLAMMATION
HIGH – SENSITIVITY C – REACTIVE PROTEIN ~ HOMOCYSTEINE ~ FIBRINOGEN
PRO – INFLAMMATORY CYTOKINES (IMMUNOSORBENT ASSAY)
UNFORTUNATELY, HOWEVER, THESE BIOMARKERS ARE COMMON TO
ALL INFLAMMATORY CONDITIONS AND ARE THEREFORE NONSPECIFIC
FURTHERMORE, THEY NEITHER DIFFERENTIATE
BETWEEN ACUTE AND CHRONIC INFLAMMATION
NOR DEMONSTRATE LOW – GRADE INFLAMMATION
NONETHELESS, THEY CAN BE USED BOTH TO
PROVIDE A BALLPARK ESTIMATE OF THE LEVEL
OF GENERALIZED INFLAMMATION IN THE BODY
AND TO MONITOR TREATMENT PROGRESS
AS NOTED EARLIER
THESE SYSTEMIC INFLAMMATORY BIOMARKERS HAVE BEEN FOUND
TO BE ELEVATED IN ABOUT ONE THIRD OF DEPRESSED PATIENTS
WHICH MAKES POSSIBLE THE TAILORING OF TREATMENTS
FOR DEPRESSION THAT SPECIFICALLY TARGET INFLAMMATION
31
32. 32
… a subgroup of individuals with depression have
evidence of increased inflammatory biomarkers and
it is in these individuals that anti-inflammatory agents
show promise for reducing depressive symptoms …
(Raison 2016)
33. NATURAL NEUROPROTECTIVE ANTI – INFLAMMATORIES
AS EITHER MONOTHERAPY OR ADJUNCTIVE THERAPY FOR DEPRESSION
A KETOGENIC DIET (HIGH IN HEALTHY FATS / LOW IN CARBS)
ORGANIC RAW NUTS (MACADAMIAS AND PECANS)
OMEGA – 3 FATTY ACIDS
“BALANCED” COMBINATION OF EICOSAPENTAENOIC ACID (EPA) /
DOCOSAHEXAENOIC ACID (DHA) / GAMMA – LINOLENIC ACID (GLA) / VITAMIN E
CURCUMIN (TURMERIC) NEUTRALIZES INFLAMMATION – CAUSING
FREE RADICALS WITH A FLOOD OF ANTIOXIDANTS
VAGUS NERVE STIMULATION ~ MEDITATION ~ MERIDIAN TAPPING
YOGA ~ DEEP (ABDOMINAL) BREATHING
ALL OF WHICH INDUCE THE RELAXATION RESPONSE BY STIMULATING THE
VAGUS NERVE, THEREBY TRIGGERING THE RELEASE OF ACETYLCHOLINE
AND INITIATION OF THE CHOLINERGIC ANTI – INFLAMMATORY PATHWAY
(ROSAS – BALLINA AND TRACEY 2009)
SHEDDING TEARS RELEASES PRO – INFLAMMATORY CYTOKINES
GARLIC ~ GINGER ~ CINNAMON ~ GREEN TEA ~ RESVERATROL
SUNSHINE ~ VITAMIN D ~ VITAMIN A
AEROBIC EXERCISE AND STRENGTH TRAINING 33
34. 34
bipolar patients on high-dose lithium carbonate (e.g., 900 – 1,500 mg / day)
have recently been found to have a reduced incidence of Alzheimer’s disease
this and other findings have led researchers to hypothesize that lithium
(whether at its standard dose or in trace amounts)
is powerfully anti-inflammatory and therefore neuroprotective
so even low-dose lithium orotate (e.g., 5 – 20 mg / day)
may well have “cognitive benefits for dementia prevention”
(Mauer et al. 2014)
35. ~ ANTI – INFLAMMATORY HERBS AND COOKING SPICES ~
CURCUMIN (A COMPOUND IN TURMERIC); CELERY SEED; GINGER; CINNAMON;
GARLIC; CLOVES; CAYENNE (RED PEPPER); CAPSAICIN (A COMPOUND IN
CHILI PEPPERS); BLACK PEPPER; ROSEMARY; BARBERRY; OREGANO;
SAGE; THYME; HOLY BASIL; CHINESE SKULLCAP ROOT
FLAVORING YOUR MEALS WITH ANTI – INFLAMMATORY HERBS AND SPICES
ENABLES YOU TO UPGRADE YOUR FOOD WITHOUT ADDING A SINGLE CALORIE
~ ANTI – INFLAMMATORY SUPPLEMENTS ~
WHITE WILLOW BARK; PYCNOGENOL (PINE BARK); RESVERATROL (FROM GRAPES);
GRAPE SEED EXTRACT; BOSWELLIA SERRATA RESIN; CAT’S CLAW; ALPHA LIPOIC ACID
~ ANTI – INFLAMMATORY FOODS ~
OMEGA – 3 ESSENTIAL FATTY ACIDS (SALMON AND SARDINES); OLIVE OIL;
WHOLE GRAINS (NOT REFINED GRAINS LIKE WHITE BREAD, WHITE RICE, AND PASTA);
DARK LEAFY GREENS (SPINACH, KALE, BROCCOLI, AND COLLARD GREENS); BEETS;
NUTS (ALMONDS AND WALNUTS); BERRIES (BLUEBERRIES AND RASPBERRIES);
TART CHERRIES; GREEN TEA; FERMENTED FOODS; ONIONS; SHIITAKE MUSHROOMS
~ ANTI – INFLAMMATORY ACTIVITIES ~
EXERCISE; DEEP BREATHING; YOGA AND PILATES; TAPPING (EFT); MEDITATION (FOCUSED
AWARENESS ON THE PRESENT MOMENT); OTHER MINDFULNESS – BASED STRESS
REDUCTION PRACTICES (FOCUSED ATTENTION ON THE BREATH OR BODILY SENSATIONS
AND PROGRESSIVE RELAXATION); SOCIAL SUPPORT; LOVEMAKING (PRODUCTION OF
ANTI – INFLAMMATORIES LIKE OXYTOCIN AND BETA – ENDORPHINS); SUNSHINE
(WHICH STIMULATES THE PRODUCTION OF VITAMIN D, WHICH IN TURN INSTRUCTS
THE IMMUNE SYSTEM TO TURN OFF ITS INFLAMMATORY RESPONSE); SLEEP 35
36. UNLIKE MOST MEDICAL CONDITIONS
FOR WHICH THERE ARE PATHOGNOMONIC LAB TESTS
PSYCHIATRIC CONDITIONS HAVE
NO OBVIOUS ORGANIC BASIS AND ARE
DIAGNOSED SIMPLY ON THE BASIS OF
“CLINICAL PHENOMENOLOGY”
(THE PATIENT’S SELF – REPORT)
THE PATIENT COMES IN AND SAYS
“I’M FEELING REALLY DOWN AND
I’VE BEEN FEELING THAT WAY FOR SOME TIME NOW.
I DON’T HAVE MUCH INTEREST IN ANYTHING.
I HAVE TROUBLE SLEEPING, NOT MUCH APPETITE,
AND LOW ENERGY.”
AND THE PSYCHIATRIST DECLARES
“YOU’RE DEPRESSED!”
36
37. DEPRESSION IS AN
INCREDIBLY COMMON MENTAL DISORDER
THE WORLD HEALTH ORGANIZATION ESTIMATES
THAT ~350,000,000 PEOPLE SUFFER FROM IT
IT IS THE LEADING CAUSE
OF DISABILITY WORLDWIDE
AND A MAJOR CONTRIBUTOR TO THE
OVERALL GLOBAL BURDEN OF DISEASE
NEARLY 1 IN 4 WOMEN AND 1 IN 6 MEN
WILL HAVE EXPERIENCED DEPRESSION
AT SOME POINT DURING THEIR LIFETIME
AND MORE THAN HALF OF THESE PEOPLE
WILL HAVE RECURRENT EPISODES
37
38. DEPRESSION OR DEPRESSIONS?
SO MANY DIFFERENT KINDS OF DEPRESSION
MAJOR DEPRESSIVE DISORDER (MDD) ~ MAJOR DEPRESSIVE EPISODE (MDE)
ACUTE DEPRESSION ~ CHRONIC DEPRESSION
DYSTHYMIC DISORDER ~ CYCLOTHYMIC DISORDER
SEASONAL AFFECTIVE DISORDER (SAD)
PREMENSTRUAL DYSPHORIC DISORDER (PMDD)
POSTPARTUM DEPRESSION ~ PERIMENOPAUSAL MELANCHOLIA
ATYPICAL DEPRESSION ~ PSYCHOTIC DEPRESSION
BIPOLAR DISORDER (MANIC DEPRESSION) ~ UNIPOLAR DISORDER
AGITATED DEPRESSION ~ RETARDED DEPRESSION
ENDOGENOUS DEPRESSION ~ EXOGENOUS DEPRESSION
REACTIVE DEPRESSION ~ SITUATIONAL DEPRESSION
SUBSTANCE – INDUCED MOOD DISORDER
MOOD DISORDER RESULTING FROM A MEDICAL CONDITION
UNFORTUNATELY, “DEPRESSION” IS SO ILL – DEFINED AND
ENCOMPASSES SUCH A HETEROGENEOUS GROUP OF
DISORDERS THAT EMPIRICAL STUDIES OFTEN PRODUCE
RESULTS THAT ARE NOT REPRODUCIBLE AND / OR
GIVE RISE TO ENTIRELY DIFFERENT CONCLUSIONS
38
39. 39
… a pervasive limitation in existing research is the
heterogeneity inherent in depression studies, which
impacts the validity of biomarker data …
(Young et al. 2016)
40. AS A “PSYCHOANALYTIC” ASIDE
ANGRY, GUILT – RIDDEN DEPRESSIONS
ACCOMPANIED BY GUILT AND
A SENSE OF ONESELF AS “BAD”
WORKED THROUGH IN THERAPY
BY HELPING THE PATIENT RAGE
EMPTY, SHAME – FILLED DEPRESSIONS
ACCOMPANIED BY SHAME AND
A SENSE OF ONESELF AS “NOT GOOD ENOUGH,”
AS “LACKING SOMEHOW,”
OR AS “FALLING SHORT OF EXPECTATIONS”
WORKED THROUGH IN THERAPY
BY HELPING THE PATIENT GRIEVE
40
41. THE MOST COMPELLING DEFINITION OF
DEPRESSION
“A GENETIC – NEUROCHEMICAL DISORDER
REQUIRING A STRONG ENVIRONMENTAL TRIGGER
AND CHARACTERIZED BY
AN INABILITY TO APPRECIATE SUNSETS”
(SAPOLSKY 1998)
INTERESTINGLY, BECAUSE SUFFERERS TEND TO
SEE THE WORLD IN A DISTORTED (NEGATIVE) WAY,
COGNITIVE THERAPISTS CONSIDER DEPRESSION TO BE
NOT A DISORDER OF AFFECT
CHARACTERIZED BY EMOTIONAL DISTRESS AND IRRITABILITY
BUT A DISORDER OF THOUGHT
CHARACTERIZED BY EXAGGERATEDLY NEGATIVE SELF – PERCEPTIONS
41
43. 43
PAST EXPERIENCE BECOMES A FILTER THROUGH
WHICH WE NOW PERCEIVE THE WORLD
WHAT ARE THE WORDS
APPEARING IN THE RED
TRIANGLES?
IF YOU THINK THEY SAY
“ONCE UPON A TIME” AND
“SHOT IN THE DARK,”
THINK AGAIN
PRIOR LEARNING PROMPTS
US TO SEE THE WORLD
AS WE EXPECT IT TO BE,
NOT AS IT REALLY IS
ONCE A SCHEMA IS IN PLACE
AND THE CUES AROUND
US LOOK “RIGHT ENOUGH,”
WE ARE BLIND TO
DETAILS AND CONTEXT
WE AUTOMATICALLY PROCESS INFORMATION AS WE EXPECT
IT TO APPEAR, WITHOUT INVESTING ANY MENTAL EFFORT
44. ANOTHER DISCLAIMER
BECAUSE I DID MY PSYCHIATRIC TRAINING
AT THE HARVARD MEDICAL SCHOOL TEACHING HOSPITAL
THAT WAS HOME TO JOSEPH SCHILDKRAUT,
FATHER OF THE “CATECHOLAMINE THEORY OF DEPRESSION,”
FOR ANY PATIENT WHO PRESENTED WITH DEPRESSION,
I WAS TAUGHT TO THINK “ANTIDEPRESSANT”
TO CORRECT FOR “CHEMICAL IMBALANCES” IN THE BRAIN
NOT THAT THE UNDERLYING CAUSES OF THOSE CHEMICAL
IMBALANCES WERE EVER SPECIFICALLY ADDRESSED
INDEED, IT WAS OVER 50 YEARS AGO THAT SCHILDKRAUT FIRST
ADVANCED HIS THEORY THAT DEPRESSION WAS CORRELATED
WITH DECREASED LEVELS OF NEUROTRANSMITTERS IN THE BRAIN
SEROTONIN, NOREPINEPHRINE, AND DOPAMINE
AND THAT ANTIDEPRESSANTS WORKED BY EFFECTIVELY
INCREASING THEIR “FUNCTIONAL” LEVELS
WHETHER BY INCREASING THEIR SYNTHESIS,
PREVENTING THEIR BREAKDOWN, OR INHIBITING THEIR REUPTAKE
44
45. IN FACT
THE ORIGINAL 1965 PAPER BY SCHILDKRAUT
IS THE MOST FREQUENTLY CITED
OF ALL ARTICLES EVER PUBLISHED
IN THE AMERICAN JOURNAL OF PSYCHIATRY
AND ONE OF THE MOST FREQUENTLY CITED
PAPERS IN ALL OF PSYCHIATRY
WE WERE NOT SUPPOSED TO BE CONCERNED THAT
ONLY ONE THIRD OF OUR DEPRESSED PATIENTS WERE GETTING BETTER,
ONE THIRD STAYING THE SAME, AND ONE THIRD ACTUALLY GETTING WORSE
NOR WERE WE SUPPOSED TO WONDER WHY IT WOULD BE THAT ALTHOUGH
ANTIDEPRESSANTS IMMEDIATELY INCREASED NEUROTRANSMITTER LEVELS,
IT USUALLY TOOK A FEW WEEKS BEFORE PATIENTS WOULD FEEL BETTER
AND WITH RESPECT TO THE VARIOUS ANTIDEPRESSANT SIDE EFFECTS,
INSTEAD OF BEING TAUGHT THAT THOSE SIDE EFFECTS WERE THE
BODY’S WAY OF SIGNALING “PROTEST,” WE WERE TAUGHT TO
DISREGARD THE “WISDOM OF THE BODY” AND INSTEAD TO REASSURE OUR
PATIENTS THAT THEIR SIDE EFFECTS WOULD SIMPLY “PASS” IN TIME
45
46. NOR DID WE UNDERSTAND THEN WHAT WE HAVE SINCE COME TO KNOW, NAMELY,
THAT CERTAIN ANTIDEPRESSANTS MAY BE A RISK FACTOR FOR
THE DEVELOPMENT OF IRREVERSIBLE COGNITIVE IMPAIRMENT
TRICYCLICS IN PARTICULAR
(AMITRIPTYLINE, IMIPRAMINE, AND DOXEPIN)
NOT ONLY INCREASE LEVELS OF SEROTONIN
AND NOREPINEPHRINE IN THE BRAIN
(WHICH IS THE DESIRED EFFECT)
BUT ALSO BLOCK THE ACTION OF ACETYLCHOLINE
(WHICH IS AN UNDESIRABLE SIDE EFFECT)
A 2015 PROSPECTIVE COHORT STUDY CONCLUDED THAT
“HIGHER CUMULATIVE ANTICHOLINERGIC USE” IS
ASSOCIATED WITH AN “INCREASED RISK FOR DEMENTIA”
INCLUDING TRICYCLIC ANTIDEPRESSANTS, CERTAIN ANTIHISTAMINES,
AND MEDICATIONS TO CONTROL AN OVERACTIVE BLADDER
(GRAY et al. 2015)
PERHAPS NOT ENTIRELY SURPRISING BECAUSE, IN ADDITION TO
DROWSINESS, DRY MOUTH, URINARY RETENTION, AND CONSTIPATION,
AT THE TOP OF THE LIST OF ANTICHOLINERGIC SIDE EFFECTS
ARE CONFUSION AND PROBLEMS WITH REASONING / SHORT – TERM MEMORY
46
47. SO I WAS TAUGHT THE MAINSTREAM
APPROACH TO TREATING DEPRESSION,
WHICH DOES NOT ATTEMPT TO FERRET OUT
UNDERLYING DISEASE PROCESSES,
BUT, RATHER, TREATS THE SYMPTOMS AND SIGNS WITH
ALLOPATHIC DRUGS DESIGNED TO PRODUCE EFFECTS
OPPOSITE TO THOSE PRODUCED BY THE DISEASE
IN OTHER WORDS, TREATMENT INVOLVES OFFERING
ANTI – SYMPTOM MEDICATIONS TO PROVIDE SYMPTOMATIC RELIEF
A DOWNSTREAM, RATHER THAN AN UPSTREAM, APPROACH
IF THE PATIENT HAS A FEVER, GIVE HER AN ANTIPYRETIC
A COUGH, AN ANTITUSSIVE
HIGH BLOOD PRESSURE, AN ANTIHYPERTENSIVE
NAUSEA AND VOMITING, AN ANTIEMETIC
IF THE PATIENT’S MOTHER HAS JUST DIED
AND THE PATIENT IS DEPRESSED,
GIVE HER A PILL SO SHE WON’T FEEL SO BAD ABOUT IT
(STARK 2006) 47
48. BUT AS JONATHAN WRIGHT IS WONT TO SAY
SIMPLY ATTEMPTING TO ELIMINATE A SYMPTOM
INSTEAD OF DEALING WITH ITS UNDERLYING CAUSES
IS LIKE PUTTING THE LID ON A BOILING POT OF WATER
TO KEEP IT FROM SPILLING OVER
INSTEAD OF TURNING OFF THE STOVE
OR COVERING AN ILLUMINATED INDICATOR LIGHT
ON YOUR CAR’S INSTRUMENT PANEL
SO THAT IT IS NO LONGER VISIBLE
INSTEAD OF DEALING WITH YOUR CAR’S
UNDERLYING MECHANICAL ISSUES
48
49. BUT BECAUSE I HAVE BECOME
OVER THE COURSE OF THE PAST 25 YEARS
A HOLISTIC ~ INTEGRATIVE ~ FUNCTIONAL MEDICINE
COMPLEMENTARY AND ALTERNATIVE ~ ENVIRONMENTAL
PSYCHIATRIST / PSYCHOANALYST
I NOW RARELY CONSIDER ANTIDEPRESSANTS TO BE
THE FIRST LINE OF DEFENSE AGAINST DEPRESSION
RATHER
MY INTEREST LIES IN FERRETING OUT
THE UNDERLYING DYSREGULATION – INDUCING
ENVIRONMENTAL STRESSORS
PSYCHOLOGICAL ~ PHYSIOLOGICAL ~ ENERGETIC
INTRINSIC ~ EXTRINSIC
ENVIRONMENTAL TOXICITIES (“TOO MUCH BAD”)
ENVIRONMENTAL DEFICIENCIES (“NOT ENOUGH GOOD”)
THE CUMULATIVE IMPACT OF WHICH
HAS GIVEN RISE TO DEPRESSION 49
50. STARK REALITY
STRESS CAUSES ALL SORTS OF THINGS BAD
INCLUDING MAKING YOU SO SAD
‘CAUSE WHEN IT’S CHRONIC
YOUR MIND IT GETS SICK
PLEASE DON’T THINK I’M STARK RAVING MAD
(STARK 2016)
50
51. TODAY I WILL BE PROPOSING A
“UNIFIED INTERDISCIPLINARY THEORY OF DEPRESSION”
ONE THAT CONCEIVES OF DEPRESSION AS A
STRESS – INDUCED DYSREGULATED STATE
OF MindBrain USUALLY ACCOMPANIED
AT LEAST SECONDARILY
BY STRESS – INDUCED DYSREGULATION
OF ALL THE BODY’S REGULATORY SYSTEMS
MOST NOTABLY, THE NERVOUS, ENDOCRINE, AND IMMUNE SYSTEMS
INTERDEPENDENT REGULATORY SYSTEMS
THAT USE EXTENSIVE “CROSSTALK” TO MAINTAIN HOMEOSTASIS
FOR THE PATIENT TO BE IN A STATE OF
MENTAL AND PHYSICAL WELL – BEING,
THESE REGULATORY SYSTEMS MUST BE
FUNCTIONING WELL NOT ONLY INDIVIDUALLY
BUT ALSO IN RELATION TO ONE ANOTHER
51
52. BUT THE MOST IMPORTANT
OF THE BODY’S REGULATORY SYSTEMS IS THE
GROUND REGULATION SYSTEM
ALSO KNOWN AS THE
CONNECTIVE TISSUE MATRIX ~ EXTRACELLULAR MATRIX
MILIEU INTERIEUR ~ INTERNAL ENVIRONMENT ~ BIOLOGICAL TERRAIN
WEB OF LIFE ~ LIVING MATRIX ~ DIVINE MATRIX
THIS GROUND REGULATION SYSTEM
IS AN INTRICATE WEB OF
INTERDEPENDENT CONNECTIVE TISSUE
THAT EXTENDS FROM
THE SURFACE OF THE BODY
TO ITS INNERMOST RECESSES,
ULTIMATELY PENETRATING
EVERY SINGLE CELL IN THE BODY
ASTOUNDINGLY, THIS REGULATORY SYSTEM IS OFTEN IGNORED
AND HAS NO “MEDICAL SPECIALTY” DEVOTED TO ITS CARE
(THE CLOSEST “DISCIPLINES” BEING OSTEOPATHY AND PHYSIATRY)
52
53. WALTER B. CANNON (1932) AND HANS SELYE (1936)
ADVANCED THE IDEA THAT THE MAINTENANCE OF
HOMEOSTASIS INVOLVED REGULATORY ORGAN SYSTEMS
MOST NOTABLY, THE NERVOUS AND ENDOCRINE SYSTEMS
IT WAS NOT UNTIL FOUR DECADES LATER THAT
THE HISTOLOGIST ALFRED PISCHINGER (1975) WAS ABLE TO
DEMONSTRATE THAT NERVE ENDINGS AND CAPILLARY BEDS
NEVER ACTUALLY HAVE DIRECT CONTACT
WITH FUNCTIONING (PARENCHYMAL) CELLS
RATHER, THE NERVOUS AND ENDOCRINE SYSTEMS
COMMUNICATE WITH THESE CELLS ONLY BY WAY OF
THE INTERVENING GROUND REGULATION SYSTEM
A GLOBAL COMMUNICATION SYSTEM IN WHICH ALL THE BODY’S
ORGAN SYSTEMS, TISSUES, AND CELLS ARE EMBEDDED
AND THROUGH WHICH ALL “MESSENGER SIGNALS” FLOW
IT IS THEREFORE THIS SYSTEM THAT IS FUNDAMENTALLY
THE MOST IMPORTANT REGULATORY SYSTEM OF ALL
BECAUSE THIS SYSTEM MUST BE FUNCTIONING PROPERLY IF THE BODY’S
OTHER REGULATORY SYSTEMS ARE TO DO THEIR JOBS EFFECTIVELY 53
54. IN THE LANGUAGE OF SOLID – STATE PHYSICS
BECAUSE THIS GROUND REGULATION SYSTEM
IS A HIGHLY ORDERED ARRAY OF MOLECULES
IMMERSED IN SALT WATER
AN ARRAY OF MOLECULES THAT IS
CLOSELY PACKED AND TIGHTLY ORGANIZED
IN A CRYSTAL – LIKE LATTICE STRUCTURE
IT HAS THE SEMICONDUCTING
PROPERTIES OF A LIQUID CRYSTAL
WHICH MAKES OF IT AN IDEAL CANDIDATE
FOR THE NEAR – INSTANTANEOUS FLOW OF
REGULATORY INFORMATION AND VIBRATORY ENERGY
THROUGHOUT THE ENTIRE SYSTEM
54
55. THIS “DIVINE MATRIX” (BRADEN 2008) HAS BEEN DESCRIBED AS
“INTELLIGENT ENERGY WITH CONSCIOUSNESS ATTACHED TO IT”
OPTIMAL FUNCTIONALITY OF WHICH REQUIRES THAT IT BE KEPT
UNCONGESTED
ENERGETICALLY UNBLOCKED
NUTRIENT – RICH
WELL – OXYGENATED
ALKALINE
ELECTRON – RICH
WELL – HYDRATED
ADEQUATELY METHYLATED
ELECTROLYTE – BALANCED
STRUCTURALLY ALIGNED
WELL – RESTED
RELAXED
EMOTIONALLY UNENCUMBERED
THIS GROUND REGULATION SYSTEM CONSTITUTES A BODY CONSCIOUSNESS
WORKING IN TANDEM WITH THE CONSCIOUSNESS OF THE MindBrain
55
56. IT COULD BE SAID THAT
THE HALLMARK OF A HEALTHY SYSTEM IS
ITS CAPACITY TO COPE WITH STRESS,
WHICH WILL BE A REFLECTION OF ITS ABILITY
TO PROCESS, INTEGRATE, AND ADAPT TO
THE IMPACT OF THE MYRIAD
ENVIRONMENTAL STRESSORS TO WHICH
IT IS BEING CONTINUOUSLY EXPOSED,
WHICH WILL BE A REFLECTION OF
THE UNDERLYING ORDEREDNESS OF
THE GROUND REGULATION SYSTEM
AND THE RESULTANT EASE WITH WHICH
INFORMATION AND ENERGY CAN BE
TRANSMITTED THROUGHOUT ITS EXPANSE
INDEED
STRESS TOLERANCE IS THE KEY
TO LONGEVITY AND HEALTHY AG(E)ING
56
57. BUT WHEN THE GROUND REGULATION SYSTEM
BECOMES DYSREGULATED BECAUSE OF THE
CUMULATIVE IMPACT OF ENVIRONMENTAL STRESSORS
THAT CANNOT BE ADEQUATELY PROCESSED AND INTEGRATED,
NO LONGER CAN THE ORDEREDNESS OF ITS INFRASTRUCTURE
BE MAINTAINED AND, AS A RESULT, NO LONGER CAN THERE BE
EASE OF FLOW OF INFORMATION AND ENERGY
THROUGHOUT ITS EXPANSE
THE NET RESULT OF THIS
STRESS – INDUCED DYSREGULATION
WILL BE “LACK OF ORDEREDNESS”
AND “DISRUPTED EASE OF FLOW”
MANIFESTING ULTIMATELY AS
PSYCHIATRIC AND MEDICAL
“DIS – ORDER” / “DIS – EASE”
(STARK 2008, 2012, 2014)
57
58. TO REVERSE THE UNDERLYING DYSFUNCTION
THE ORDEREDNESS AND FLUIDITY OF THE
GROUND REGULATION SYSTEM MUST BE
RESTORED WITH TARGETED THERAPIES THAT
AS NOTED EARLIER
“LIGHTEN THE LOAD”
TO CORRECT FOR TOXICITIES
AND “REPLENISH THE RESERVES”
TO CORRECT FOR DEFICIENCIES
ALL WITH AN EYE TO “FACILITATING THE FLOW”
OF INFORMATION AND ENERGY
THROUGHOUT THE LIVING SYSTEM
BE THAT “INTELLIGENT ENERGY” IN THE FORM OF “CHEMICAL MESSENGERS”
(HORMONES ~ CYTOKINES ~ NEUROTRANSMITTERS)
OR “ENERGY QUANTA” (BIOPHOTONS)
THEREBY RESTORING HOMEOSTATIC BALANCE, RESILIENCE,
AND THE CAPACITY TO COPE WITH THE STRESS OF LIFE
(STARK 2008, 2012, 2015a, 2015b) 58
59. FOR THE MOMENT
LET US THINK OF THE LIVING SYSTEM AS A
COMPLEX ADAPTIVE,
SELF – ORGANIZING (CHAOTIC) SYSTEM
COMPLEX – INTRICATE INTERDEPENDENCE
OF THE SYSTEM’S COMPONENTS
ADAPTIVE – THE CAPACITY TO LEARN FROM EXPERIENCE
SELF – ORGANIZING – THE SPONTANEOUS EMERGENCE
OF SYSTEM – WIDE PATTERNS ARISING FROM
INTERPLAY OF THE SYSTEM’S COMPONENTS
CHAOTIC – DESPITE THE SYSTEM’S APPARENT RANDOMNESS,
AN UNDERLYING ORDEREDNESS THAT WILL
EMERGE OVER TIME AS THE SYSTEM EVOLVES
OR, WHEN OUR FOCUS IS ON STRESS – INDUCED DYSREGULATION,
AN UNDERLYING (AND FAIRLY “ROBUST”)
DIS – ORDEREDNESS THAT WILL
EMERGE OVER TIME AS THE SYSTEM DEVOLVES
59
60. ALL HEALTHCARE PRACTITIONERS
SHOULD KEEP IN MIND THAT
“SELF – ORGANIZING SYSTEMS
(INCLUDING US)
RESIST PERTURBATION”
(KREBS 2013)
WHETHER ORDERED OR DIS – ORDERED,
FUNCTIONAL OR DYSFUNCTIONAL,
WELL – REGULATED OR DYSREGULATED,
THE LIVING SYSTEM WILL RESIST CHANGE
THUS THE IMPORTANCE OF “OPTIMALLY STRESSFUL”
THERAPEUTIC INTERVENTIONS STRATEGICALLY DESIGNED
TO PROVOKE A “STUCK” SYSTEM’S CAPACITY TO
SELF – CORRECT IN THE FACE OF MANAGEABLE CHALLENGE
PRECIPITATING DISRUPTION
IN ORDER TO TRIGGER REPAIR 60
61. THE THERAPEUTIC USE OF OPTIMAL STRESS
TO PROVOKE RECOVERY
DEPRIVING ONESELF OF HALF A NIGHT’S SLEEP ONCE A WEEK
PREFERABLY THE SECOND HALF OF THE NIGHT (FOR EXAMPLE, FROM 3 TO 7 AM)
CAN PRODUCE A RAPID, EVEN IF SHORT – LIVED,
RESTABILIZATION OF MOOD AND RECOVERY FROM DEPRESSION
THE “STRESS” OF INTERRUPTING NORMAL SLEEP PATTERNS
MAY “RESYNCHRONIZE DISTURBED CIRCADIAN RHYTHMS”
(LEIBENLUFT AND WEHR 1992)
INTERMITTENT FASTING
A 36 – HOUR WATER FAST ONCE A WEEK
(FOR EXAMPLE, FROM AFTER DINNER ON MONDAY TO BEFORE BREAKFAST ON WEDNESDAY)
CAN SO SIGNIFICANTLY REDUCE THE TOTAL BODY BURDEN
THAT MENTAL CLARITY AND FOCUS
CAN BE IMPROVED DRAMATICALLY AND
A SENSE OF OVERALL WELL – BEING RESTORED
IT IS ALSO ASSOCIATED WITH INCREASED LEVELS OF
BRAIN – DERIVED NEUROTROPHIC FACTOR (BDNF)
DEPLETED LEVELS OF WHICH ARE THOUGHT TO BE ASSOCIATED WITH DEPRESSION
(MATTSON 2015) 61
62. ACUTE STRESS CAN “OPTIMIZE”
BY PROVOKING “HEIGHTENED FUNCTIONALITY,”
A RESULT OF THE BODY’S “ADAPTIVE UPREGULATION”
IN FACT
SUPERIMPOSING AN ACUTE INJURY ON TOP OF
A CHRONIC ONE IS SOMETIMES EXACTLY
WHAT THE BODY NEEDS IN ORDER TO HEAL
MORE SPECIFICALLY
OFFERING AN
OPTIMALLY STRESSFUL CHALLENGE
THAT INITIALLY “DESTABILIZES”
A “DIS – ORDERED” SYSTEM
IS SOMETIMES THE MAGIC INGREDIENT
NEEDED TO PROVOKE HEALING
AND “RESTABILIZATION” OF THE SYSTEM
AT A HIGHER LEVEL OF INTEGRATION,
BALANCE, AND “ORDEREDNESS”
62
63. IN MY WORK AS A PSYCHOANALYST
AGAINST THE BACKDROP OF AN EMPATHICALLY ATTUNED
AND AUTHENTICALLY ENGAGED THERAPY RELATIONSHIP
I OFFER OPTIMALLY STRESSFUL INTERVENTIONS PAINSTAKINGLY
FORMULATED TO PROVIDE JUST THE RIGHT COMBINATION OF
(DESTABILIZING) CHALLENGE AND (RESTABILIZING) SUPPORT
AS SUCH
THEY ARE INITIALLY ANXIETY – PROVOKING
BUT ULTIMATELY HEALTH – PROMOTING
BY TAPPING INTO THE BODY’S RESILIENCE AND
INNATE CAPACITY TO SELF – STABILIZE
IN THE FACE OF THERAPEUTIC STRESS, THESE
“CONFLICT STATEMENTS” ARE CUSTOM DESIGNED TO
PRECIPITATE DISRUPTION IN ORDER TO TRIGGER REPAIR
“YOU KNOW THAT EVENTUALLY YOU WILL NEED TO START EATING MORE
HEALTHILY IF YOU ARE EVER TO GET BETTER; BUT, FOR NOW, YOU
FIND YOURSELF FEELING OVERWHELMED AT THE THOUGHT OF HAVING
TO GIVE UP ONE OF THE FEW REMAINING PLEASURES IN YOUR LIFE.”
63
64. SO ACUTE STRESS CAN “OPTIMIZE”
BUT CHRONIC STRESS WILL “TRAUMATIZE”
THE CUMULATIVE IMPACT OF WHICH WILL CONTRIBUTE
TO EVER – INCREASING WEAR AND TEAR ON THE BODY
OVER TIME, DEPLETING THE BODY’S ADAPTATION RESERVES
(ITS NUTRIENT AND ENERGETIC RESOURCES)
HORMESIS IS THE TERM USED BY AVANT – GARDE
TOXICOLOGISTS (MATTSON AND CALABRESE 2009) TO
DESCRIBE THIS BIPHASIC RESPONSE TO STRESS
LOW – DOSE “OPTIMIZATION” / HIGHER – DOSE “TRAUMATIZATION”
ACUTE STRESS “GOOD” / CHRONIC STRESS “BAD”
ACUTE INFLAMMATION “GOOD” / CHRONIC INFLAMMATION “BAD”
“THE DIFFERENCE BETWEEN A POISON AND A MEDICATION
IS THE DOSAGE THEREOF” (PARACELSUS 2004)
ULTIMATELY, CHRONIC STRESS CAUSES DYSREGULATION
OF ALL THE BODY’S REGULATORY ORGAN SYSTEMS …
64
65. … BECAUSE, AS IS TRUE FOR ALL COMPLEX ADAPTIVE,
SELF – ORGANIZING (CHAOTIC) SYSTEMS
BASICALLY EVERYTHING IN THE BODY
AFFECTS EVERYTHING ELSE
(aka THE RIPPLE OR DOMINO EFFECT)
IN ANY EVENT
WHEN REGULATORY CAPACITY AND
HOMEOSTATIC BALANCE IN THE BODY
CANNOT BE MAINTAINED BY VIRTUE OF
THE OVERWHELMING IMPACT OF
ENVIRONMENTAL STRESSORS THAT ARE
SIMPLY “TOO MUCH” TO BE
ADEQUATELY PROCESSED AND INTEGRATED,
CHAOS AND GENERALIZED
DISTRESS WILL RESULT
65
66. SO WHAT HAPPENS WHEN THE PRIMARY DOMAIN OF
DYSREGULATION, DISTRESS, AND PAIN IS THE BRAIN?
BE IT PSYCHOLOGICAL OR PHYSIOLOGICAL
PAIN IS GENERALLY THE RESULT OF
DYSREGULATED OR OBSTRUCTED FLOW
AND
WHEN THAT DISRUPTED FLOW IS IN THE BRAIN
AS HAPPENS, FOR EXAMPLE, WHEN THE BRAIN HAS BECOME
INFLAMED BECAUSE OF STRESS – INDUCED IMMUNE ACTIVATION
THE INFLAMMATORY PAIN
THAT RESULTS MAY ULTIMATELY
MANIFEST AS DEPRESSION
66
67. MORE SPECIFICALLY, WHEN THE BRAIN IS INVOLVED …
DIS – ORDER, DIS – EASE,
AND BRAIN INFLAMMATION
WHEN REDNESS, HEAT, SWELLING, AND PAIN
AFFECT THE TERRAIN OF THE BRAIN
THE FLOW IT DISRUPTS
AND CHAOS ERUPTS
TILL ONCE AGAIN ORDER DOES REIGN
(STARK 2016)
67
68. ACUTE vs. CHRONIC INFLAMMATION
ACUTE INFLAMMATION IN RESPONSE TO STRESS
IS IN THE INTEREST OF RESTORING HOMEOSTASIS
SO ACTIVATION OF THE IMMUNE SYSTEM IS
INITIALLY ADAPTIVE AND PART OF THE SOLUTION
BUT IF THE INFLAMMATION CONTINUES INDEFINITELY,
IT WILL EVENTUALLY BECOME PART OF THE PROBLEM
“TOO MUCH OF A GOOD THING”
A PROBLEM THAT WILL LEAD ULTIMATELY TO CHRONIC DISEASE
AND, WHEN THE TARGET ORGAN IS THE BRAIN, TO DEPRESSION
IN OTHER WORDS
WHEREAS ACUTE INFLAMMATION
IS PART OF THE IMMUNE SYSTEM’S
HEALTHY RESPONSE TO STRESS,
IF THE INFLAMMATION BECOMES CHRONIC,
THE INFLAMMATION ITSELF
WILL BECOME A STRESSOR
68
69. WHICH LEADS ME TO PONDER THE FOLLOWING CONUNDRUM –
WHAT DOES IMMUNE
DYSREGULATION REALLY MEAN?
AN OVERACTIVE IMMUNE SYSTEM?
THAT IS “DOING ITS JOB TOO WELL”
AS HAPPENS, FOR EXAMPLE, WHEN YOU HAVE AN AUTOIMMUNE DISEASE
CLEARLY THE RESULT OF A DYSREGULATED IMMUNE SYSTEM
THAT IS INAPPROPRIATELY “ROBUST” AND PROTECTING ALL TOO WELL
OR AN UNDERACTIVE IMMUNE SYSTEM?
THAT IS “NOT DOING ITS JOB WELL ENOUGH”
AS HAPPENS, FOR EXAMPLE, WHEN YOU GET SICK WITH A BAD COLD
CLEARLY THE RESULT OF A DYSREGULATED IMMUNE SYSTEM
THAT IS “COMPROMISED” IN ITS FUNCTIONING, DEFICIENT, WEAK, AND INEFFECTUAL
SO IMMUNE DYSREGULATION MUST MEAN
AN IMMUNE SYSTEM THAT
IS PROVIDING INADEQUATE PROTECTION
SOMETIMES TOO MUCH AND SOMETIMES TOO LITTLE
69
70. BASED ON A COMPREHENSIVE REVIEW OF THE LITERATURE,
I HAVE DEVELOPED AN INTEGRATIVE THEORY OF DEPRESSION
THAT TAKES INTO CONSIDERATION A MULTITUDE OF FACTORS
PSYCHOSOCIAL STRESSORS
ADVERSE CHILDHOOD EXPERIENCES AND CURRENT REAL – LIFE STRESSORS
GENETIC PREDISPOSITION
IRREVERSIBLE MUTATIONS AND POLYMORPHISMS
LIFESTYLE AND ENVIRONMENTAL FACTORS
REVERSIBLE EPIGENETIC MODIFICATIONS
A DYSREGULATED GUT MICROBIOME
AN IMBALANCE OF GOOD AND BAD MICROBES IN THE GASTROINTESTINAL TRACT
A DYSREGULATED CENTRAL NERVOUS SYSTEM
DEPLETED LEVELS OF SEROTONIN, NOREPINEPHRINE, AND DOPAMINE
A DYSREGULATED NEUROENDOCRINE SYSTEM
DYSREGULATED HYPOTHALAMIC – PITUITARY – ADRENAL AXIS
(ELEVATED LEVELS OF ANTI – INFLAMMATORY CORTISOL)
A DYSREGULATED NEUROIMMUNE SYSTEM
ACTIVATED PERIPHERAL MACROPHAGES AND CENTRAL MICROGLIA
(ELEVATED LEVELS OF PRO – INFLAMMATORY CYTOKINES)
70
71. A PSYCHO –
SOCIO –
GENO –
ENVIRO –
GASTROENTERO –
NEURO –
IMMUNO –
ENDOCRINO –
LOGIC THEORY OF DEPRESSION
(STARK 2016)
71
72. THE “PSYCHO” COMPONENT OF DEPRESSION
A MNEMONIC FOR THE SYMPTOMS AND SIGNS OF DEPRESSION
SIGeCAPS = SIG (LET IT BE LABELED) + ENERGY + CAPSules
SLEEP DISORDER (DECREASED OR INCREASED)
INTEREST DEFICIT (ANHEDONIA)
INABILITY TO EXPERIENCE PLEASURE OR ENJOY SUNSETS
GUILT (EXCESSIVE SELF – REPROACH AND REGRET)
FEELINGS OF WORTHLESSNESS AND HELPLESSNESS
ENERGY DEFICIT
FATIGUE, LOW LIBIDO, AND SOCIAL AVOIDANCE
CONCENTRATION DEFICIT
DIFFICULTY STAYING FOCUSED AND MAKING DECISIONS
APPETITE DISORDER (DECREASED OR INCREASED)
PSYCHOMOTOR RETARDATION OR AGITATION
SUICIDALITY
DESPAIR AND HOPELESSNESS 72
73. THE “PSYCHOSOCIO” COMPONENT OF DEPRESSION
PSYCHOSOCIAL STRESSORS
EXPERIENCED BY THE CHILD
IN RELATION TO THE
PARENTAL / SOCIAL ENVIRONMENT
WHETHER TRAUMA AND ABUSE (TOXICITIES)
OR DEPRIVATION AND NEGLECT (DEFICIENCIES)
ARE RISK FACTORS THAT WILL PRIME
THE CHILD FOR SUBSEQUENT DEVELOPMENT
OF DEPRESSION WHEN LATER TRIGGERED
BY STRESSFUL SOCIAL INTERACTIONS
REMINISCENT OF THE ORIGINAL TRAUMA
73
74. 74
… psychosocial stress is capable of causing
immune dysregulation and increased
neuroinflammatory signaling, which may contribute
to the development of depression …
(Ramirez et al. 2016)
75. THERE ARE SEVERAL DIFFERENT
PSYCHOSOCIAL THEORIES OF DEPRESSION
THAT PRIVILEGE EARLY LIFE ADVERSITIES AS PRIMING EVENTS
ONE OF THE BEST KNOWN OF WHICH IS ADVANCED
BY AARON BECK (1979), A COGNITIVE THERAPIST WHO
ATTRIBUTES THE ONSET AND RECURRENCE OF DEPRESSION
TO “NEGATIVE COGNITIONS” AND CORRESPONDING
“MALADAPTIVE PATTERNS OF INFORMATION PROCESSING”
HIS MODEL ADVANCES THE IDEA THAT PEOPLE WHO EXPERIENCE
ADVERSITY IN CHILDHOOD DEVELOP NEGATIVE SELF – SCHEMAS
WHICH REMAIN DORMANT UNTIL A STRESSFUL LIFE EVENT
REMINISCENT OF THE ORIGINAL STRESSOR
IS LATER ENCOUNTERED,
AT WHICH POINT THE SCHEMAS BECOME ACTIVATED AND
THEN SERVE AS FILTERS THROUGH WHICH (NEGATIVE)
“MEANING IS MADE” OF THE “NEW” EXPERIENCE
aka SELF – FULFILLING PROPHECIES
LEADING ULTIMATELY TO “DEPRESSIVE AFFECT”
AND REINFORCEMENT OF
THE PRECONCEIVED NEGATIVE COGNITIONS
75
76. PSYCHOTHERAPY WILL THEN INVOLVE
INCREASING THE PATIENT’S AWARENESS OF
NOT JUST THE PRICE SHE PAYS FOR CLINGING SO TENACIOUSLY
TO HER NEGATIVE SELF – SABOTAGING SCHEMAS (THE PAIN)
BUT ALSO THE BENEFIT SHE DERIVES FROM DOING SO (THE GAIN)
AS LONG AS THE GAIN IS GREATER THAN THE PAIN,
THE PATIENT WILL MAINTAIN THE DYSFUNCTION AND REMAIN ENTRENCHED
BUT ONCE THE PAIN BECOMES GREATER THAN THE GAIN,
THE STRESS AND STRAIN THEREBY CREATED
WILL PROVIDE THE THERAPEUTIC LEVERAGE NEEDED
FOR THE PATIENT GRADUALLY TO RELINQUISH
HER ATTACHMENT TO THE NEGATIVE SELF – SCHEMAS
THE IMPETUS FOR WHICH WILL BE HER NEED
TO RESTORE HER PSYCHOLOGICAL EQUILIBRIUM
IN ESSENCE
THERAPY WILL INVOLVE “WORKING THROUGH” THE “OPTIMAL
STRESS” GENERATED BY THE PATIENT’S EVER – INCREASING
AWARENESS OF THE “COGNITIVE DISSONANCE” BETWEEN
“COST” (PAIN) AND “BENEFIT” (GAIN), PROMPTING HER
ULTIMATELY TO “LET GO” OF HER DISTORTED PERCEPTIONS
(STARK 1999, 2014, 2015a, 2015b, 2016) 76
77. THE “GENO” COMPONENT OF DEPRESSION
THE GENOME
AN INDIVIDUAL’S UNIQUE GENETIC (DNA) MAKEUP
ARE THERE GENETIC PREDISPOSITIONS
TO DEPRESSION?
WHETHER THE RESULT OF MUTATIONS
GENETIC VARIANTS THAT ARE UNIQUE TO AN INDIVIDUAL
OR SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs)
GENETIC VARIANTS THAT ARE MORE COMMON ACROSS A POPULATION
HETEROZYGOUS SNPs
WHEN THE VARIANT AFFECTS ONLY ONE OF THE ALLELES
(BECAUSE IT WAS INHERITED FROM ONLY ONE OF THE PARENTS)
HOMOZYGOUS SNPs
WHEN THE VARIANT AFFECTS BOTH OF THE ALLELES
(BECAUSE IT WAS INHERITED FROM BOTH OF THE PARENTS)
77
78. 78
… multiple genetic factors in conjunction with
environmental factors are likely necessary for the
development of depression …
… but despite all efforts, thus far no single genetic
variation has been identified that increases the risk
of depression substantially …
(Lohoff 2010)
79. THE “GENO” COMPONENT OF DEPRESSION
… EXCEPT THAT DEPRESSION DOES TEND TO RUN IN FAMILIES AND
WOULD THEREFORE APPEAR TO HAVE SOME DEGREE OF INHERITABILITY
EVEN IF WE CANNOT YET UNDERSTAND WHY
IF A TWIN HAS MAJOR DEPRESSION, THERE IS A 50% CHANCE
THAT AN IDENTICAL TWIN WILL ALSO HAVE DEPRESSION
AND A 25% CHANCE THAT A FRATERNAL TWIN WILL
BUT IF ONLY A CERTAIN PERCENTAGE
WILL ALSO HAVE DEPRESSION,
THEN “GENETIC” MUST NOT MEAN
INEVITABILITY BUT VULNERABILITY
WHICH IS WHERE “EPIGENETICS” COMES IN
THAT IS, LIFESTYLE CHOICES AND ENVIRONMENTAL EXPOSURES
THAT REGULATE THE EXPRESSION OF GENES
EQUIPOTENTIALITY IS THE TERM USED IN SYSTEMS THEORY TO
DESCRIBE WHAT HAPPENS WHEN THINGS WITH THE SAME ORIGINAL
CONDITIONS (THE SAME “POTENTIAL”) GO IN DIFFERENT DIRECTIONS
EPIGENETIC MODIFICATIONS SPEAK TO THE IMPACT
OF THE ENVIRONMENT ON THE GENOME 79
80. THE “ENVIRO” COMPONENT OF DEPRESSION
GENE – ENVIRONMENT INTERACTIONS
(aka NATURE vs. NURTURE)
INCLUDE NOT JUST THE PARENTAL / SOCIAL ENVIRONMENT
BUT ALSO, MORE GENERALLY, THE PHYSICAL ENVIRONMENT
WHEREAS MANY ILLNESSES WERE ONCE THOUGHT TO BE
80 – 90% GENETIC AND ONLY 10 – 20% ENVIRONMENTAL,
NOW MOST ARE THOUGHT TO BE
ONLY 10 – 20% GENETIC AND 80 – 90% ENVIRONMENTAL
“EPIGENETICS”
MEANS LITERALLY “ON TOP OF GENETICS” AND REFERS TO
REVERSIBLE EXTERNAL MODIFICATIONS OF GENE EXPRESSION
AND NOT TO ALTERATIONS IN THE GENETIC CODE ITSELF
IN OTHER WORDS, EPIGENETIC MODIFICATIONS CHANGE NOT
THE SEQUENCE OF NUCLEOTIDES IN THE DNA STRAND
BUT THE PHYSICAL STRUCTURE OF THE DNA
SUCH THAT HOW THE GENES ARE “READ” BECOMES MODIFIED
ONE EXAMPLE OF WHICH IS DNA METHYLATION
(THE ADDITION OF A METHYL GROUP TO PART OF THE DNA MOLECULE)
WHICH CAN PREVENT A GENE FROM BEING EXPRESSED 80
81. LIFESTYLE CHOICES THAT CAN INDUCE EPIGENETIC MODIFICATIONS
STRESSORS CONTRIBUTING TO THE ALLOSTATIC LOAD
SUGAR; HIGH GLYCEMIC LOAD (CAUSED BY FOODS THAT RAISE THE BLOOD SUGAR
LEVEL); REFINED AND PROCESSED FOODS; SATURATED AND TRANS FATTY ACIDS; FOOD
ADDITIVES (ARTIFICIAL COLORINGS, SWEETENERS, AND FLAVORINGS; MONOSODIUM
GLUTAMATE (MSG); SODIUM BENZOATE; HIGH FRUCTOSE CORN SYRUP); CAFFEINE, NICOTINE,
AND ALCOHOL; LOW – FIBER DIET; PRESCRIPTION AND RECREATIONAL DRUGS; NATURAL
GAS STOVES; WATER BEDS AND ELECTRIC BLANKETS; POOR QUALITY SLEEP; LIVING
CLOSE TO MAJOR HIGHWAYS AND INTERSECTIONS; SEDENTARY LIFESTYLE; OBESITY;
TELEVISION; TOO LITTLE TIME OUTDOORS AND IN FRESH AIR; IMBALANCE BETWEEN
WORK AND PLAY; NEGATIVE THOUGHTS; CHRONIC ANGER; FINANCIAL DIFFICULTIES;
CHRONIC RELATIONSHIP CONFLICT; SOCIAL REJECTION AND ISOLATION; LONELINESS
ENVIRONMENTAL EXPOSURES THAT CAN INDUCE EPIGENETIC MODIFICATIONS
STRESSORS CONTRIBUTING TO THE ALLOSTATIC LOAD
PESTICIDES; HERBICIDES (GLYPHOSATE); PETROLEUM – BASED SOLVENTS (TOLUENE
AND BENZENE); VOLATILE ORGANIC COMPOUNDS (FORMALDEHYDE); HEAVY METALS
(MERCURY AND ALUMINUM); MOLDS AND THE DANGEROUS MYCOTOXINS THEY RELEASE;
TOBACCO SMOKE; PHTHALATES AND OTHER ENDOCRINE – DISRUPTING COMPOUNDS
(BISPHENOL A IN PLASTICS); FLAME RETARDANTS (PBDEs); AUTOMOBILE EXHAUST FUMES;
ELECTROMAGNETIC FIELDS (EMFs); HIGH VOLTAGE POWER LINES; CELL TOWERS;
CELL PHONES; SYNTHETIC FRAGRANCES (PERFUMES, AIR FRESHENERS, AND OTHER
“PLEASANT – SCENTED” PRODUCTS); NEWSPAPER PRINT; PERSONAL CARE PRODUCTS;
LAUNDRY DETERGENTS AND FABRIC SOFTENERS; HOUSEHOLD CLEANERS; ANTIBACTERIAL
SOAPS AND HAND SANITIZERS; FLUORIDE – CONTAINING WATER AND TOOTHPASTE;
MORE GENERALLY – THE MYRIAD POLLUTANTS AND ENVIRONMENTAL TOXICANTS
IN THE AIR WE BREATHE, THE WATER WE DRINK, AND THE FOOD WE EAT 81
83. THE “GASTROENTERO” COMPONENT OF DEPRESSION
THE GUT MICROBIOTA (aka THE GUT FLORA)
(THE MICROBIAL CELLS LIVING INSIDE THE GI TRACT)
AND THE MICROBIOME
(THEIR GENETIC MATERIAL)
BIDIRECTIONAL COMMUNICATION
(BOTTOM – UP FROM GUT TO BRAIN AND TOP – DOWN FROM BRAIN TO GUT)
BETWEEN THE COMPLEX GUT MICROBIAL ECOSYSTEM
AND THE BRAIN
(aka THE MICROBIOTA – GUT – BRAIN AXIS)
AN INFORMATION SUPERHIGHWAY
CONTINUOUS SIGNALING BETWEEN GUT AND BRAIN VIA MESSENGER MOLECULES
HORMONES (NEUROENDOCRINE SYSTEM)
PRO – INFLAMMATORY CYTOKINES (NEUROIMMUNE SYSTEM)
NEUROTRANSMITTERS (AUTONOMIC AND ENTERIC NERVOUS SYSTEMS)
NEUROTRANSMITTERS ARE ALSO PRODUCED BY THE GUT MICROBIOTA
WHICH PRODUCE 90% OF THE BODY’S SEROTONIN AND 50% OF THE BODY’S DOPAMINE
THE ENTERIC NERVOUS SYSTEM, WHICH RESIDES WITHIN THE WALL OF
THE DIGESTIVE TRACT, IS SOMETIMES CALLED THE “SECOND BRAIN”
BECAUSE IT IS “SMART” ENOUGH TO FUNCTION AUTONOMOUSLY
83
84. THE “GASTROENTERO” COMPONENT OF DEPRESSION
WHEN THE BALANCE OF GUT MICROBES
(GOOD AND BAD)
BECOMES DISRUPTED AND DYSBIOSIS RESULTS,
THE GUT WALL BECOMES INFLAMED AND
INTESTINAL PERMEABILITY INCREASES
(aka LEAKY GUT)
ALTHOUGH THE ACTUAL MECHANISMS OF ACTION
ARE NOT YET FULLY UNDERSTOOD,
DYSBIOSIS AND THE INFLAMMATION
THAT ACCOMPANIES IT ARE THOUGHT
TO GIVE RISE TO A BROAD RANGE
OF STRESS – RELATED PHYSICAL, MENTAL,
AND EMOTIONAL DISORDERS
(INCLUDING DEPRESSION)
84
85. 85
… deficits in intestinal permeability may underlie
the chronic low-grade inflammation observed
in disorders such as depression …
(Kelly et al. 2015)
87. THE “GASTROENTERO” COMPONENT OF DEPRESSION
THE EMERGING LINK BETWEEN THE GUT MICROBIOTA
AND THE CENTRAL NERVOUS SYSTEM OFFERS
PROMISE FOR THE DESIGN OF NOVEL TREATMENTS FOR
STRESS – INDUCED PSYCHIATRIC DISORDERS, SUCH AS DEPRESSION
THE NEW FIELD OF PSYCHOBIOTICS
PROBIOTICS THAT, WHEN INGESTED IN ADEQUATE AMOUNTS,
PRODUCE HEALTH BENEFITS IN PATIENTS
SUFFERING FROM PSYCHIATRIC ILLNESSES
PRECLINICAL EVALUATION IN RODENTS
SUGGESTS THAT CERTAIN PSYCHOBIOTICS
(MOST NOTABLY BIFIDOBACTERIUM AND LACTOBACILLUS)
MITIGATE THE STRESS RESPONSE
AND POSSESS ANTIDEPRESSANT ACTIVITY
SUCH BENEFITS MAY BE RELATED TO BOTH THEIR CAPACITY TO
REDUCE HPA AXIS ACTIVITY AND THEIR ANTI – INFLAMMATORY ACTIONS
(DINAN et al. 2013)
THE SCIENTIFIC LITERATURE HAS DEMONSTRATED THAT PSYCHOBIOTICS DO
INDEED HAVE A BROAD SPECTRUM OF THERAPEUTIC ACTIVITY; BUT
THE RESULTS ARE, SADLY, OFTEN CONTRADICTORY AND INCONCLUSIVE
87
88. THE “NEURO” COMPONENT OF DEPRESSION
BOTH THE CENTRAL AND THE AUTONOMIC NERVOUS SYSTEMS
ALREADY DISCUSSED
CENTRAL NERVOUS SYSTEM
DEPLETED LEVELS OF NEUROTRANSMITTERS IN THE BRAIN
ESPECIALLY IN THE LIMBIC SYSTEM
SEROTONIN, NOREPINEPHRINE, AND DOPAMINE
THE CATECHOLAMINE / MONOAMINE THEORY OF DEPRESSION
SEROTONIN REGULATES CALMNESS
(ALSO PROMINENT IN THE GASTROINTESTINAL TRACT)
REDUCED LEVELS OF WHICH CAUSE AN OBSESSIVE SENSE OF GUILT
NOREPINEPHRINE REGULATES ALERTNESS, CONCENTRATION, AND MOTIVATION
REDUCED LEVELS OF WHICH CAUSE PSYCHOMOTOR RETARDATION
DOPAMINE IS INVOLVED IN FEELINGS OF PLEASURE AND IS
THEREFORE CALLED THE “REWARD CHEMICAL” OF THE BRAIN
REDUCED LEVELS OF WHICH CAUSE ANHEDONIA
CHOOSE THE ANTIDEPRESSANT (SSRI / SNRI / NDRI / SNDRI)
WITH THE MECHANISM OF ACTION THAT
WILL TARGET THE MOST PROBLEMATIC SYMPTOMS
88
89. THE “NEURO” COMPONENT OF DEPRESSION
THE STRESS RESPONSE
BOTH ACUTE AND CHRONIC
IS REGULATED BY THE LIMBIC SYSTEM
AND INVOLVES BOTH THE SYMPATHETIC NERVOUS SYSTEM
AND THE HYPOTHALAMIC – PITUITARY – ADRENAL “STRESS” AXIS
MORE SPECIFICALLY
IN THE FACE OF REAL OR IMAGINED “STRESSORS,”
THE AMYGDALA IS ACTIVATED
WHICH PROCESSES EMOTIONS LIKE FEAR AND ANXIETY
THE AMYGDALA THEN SENDS A “DISTRESS SIGNAL”
TO THE HYPOTHALAMUS
WHICH IS THE “COMMAND CENTER” OF THE BRAIN AND REGULATES
BOTH THE SYMPATHETIC NERVOUS SYSTEM AND THE HPA AXIS
THE HYPOTHALAMUS THEN INITIATES
THE “STRESS RESPONSE,” WHICH ACTIVATES
THE BODY’S ENSEMBLE OF REGULATORY SYSTEMS
SO THAT HOMEOSTATIC BALANCE CAN BE RESTORED
89
90. HANS SELYE (1936) – THE FATHER OF STRESS
GENERAL ADAPTATION SYNDROME
SPEAKS TO THE BODY’S HOMEOSTATIC EFFORTS
TO PROTECT ITSELF AGAINST
ALL MANNER OF NONSPECIFIC STRESSORS
A MANIFESTATION OF WALTER B CANNON’S
“WISDOM OF THE BODY” (1932)
ALARM STAGE
HEIGHTENED AROUSAL / CALL TO ACTION
FIGHT – OR – FLIGHT
RESISTANCE / ADAPTATION STAGE
MOBILIZATION OF THE BODY’S DEFENSES
IN AN EFFORT FIRST TO RESIST AND
ULTIMATELY TO ADAPT TO THE ONGOING STRESS
EXHAUSTION STAGE
DEPLETION OF THE BODY’S RESOURCES
MALADAPTATION / DYSHOMEOSTASIS 90
91. THE “NEUROIMMUNE” COMPONENT OF DEPRESSION
STRESS ACTIVATES
NOT ONLY THE SYMPATHETIC NERVOUS SYSTEM
AND THE HYPOTHALAMIC – PITUITARY – ADRENAL AXIS
BUT ALSO THE IMMUNE SYSTEM
MACROPHAGES IN THE BODY
AND MICROGLIA IN THE BRAIN
THE “RESIDENT MACROPHAGES” IN THE CENTRAL NERVOUS SYSTEM
IMMUNE CELLS THAT ARE THEN
TRIGGERED TO RELEASE
PRO – INFLAMMATORY CYTOKINES
INTERLEUKIN (IL) – 1 ~ INTERLEUKIN (IL) – 6 ~ TUMOR NECROSIS FACTOR ALPHA
INTERFERON GAMMA
THE RELEASE OF WHICH UPREGULATES
INFLAMMATORY PROCESSES
91
92. THE “NEUROIMMUNE” COMPONENT OF DEPRESSION
THE PERIPHERAL IMMUNE (BODY) AND
NEUROIMMUNE (BRAIN) SYSTEMS
ARE STRUCTURALLY DISTINCT
ALTHOUGH ONCE THOUGHT TO BE “IMMUNE PRIVILEGED,”
THE BRAIN IS NOW KNOWN TO HAVE
A ROBUST NEUROIMMUNE SYSTEM
COMPOSED PREDOMINANTLY OF GLIAL CELLS
MICROGLIA ~ ASTROCYTES ~ OLIGODENDROCYTES
WHICH MAKE UP ALMOST
90% OF THE CELLS IN THE BRAIN
THESE GLIAL CELLS ARE THE BRAIN’S
“CONNECTIVE TISSUE”
(AS SUCH, THEY ARE PART OF THE GROUND REGULATION SYSTEM)
92
93. THE “NEUROIMMUNE” COMPONENT OF DEPRESSION
THE NEUROINFLAMMATORY
THEORY OF DEPRESSION
(SETIAWAN et al. 2015)
POSITRON EMISSION TOMOGRAPHY (PET) SCANS WERE DONE
ON 20 PATIENTS WITH DEPRESSION AND 20 HEALTHY CONTROLS
INCREASED DENSITY OF TRANSLOCATOR PROTEIN
A GLIAL PROTEIN USED AS A BIOMARKER OF BRAIN INFLAMMATION
WAS FOUND IN THE PREFRONTAL CORTEX,
NUCLEUS ACCUMBENS, AND INSULA
OF THE BRAINS OF THE DEPRESSED PATIENTS
THE RESEARCHERS CONCLUDED
“THIS FINDING PROVIDES THE MOST COMPELLING
EVIDENCE TO DATE OF BRAIN INFLAMMATION AND,
MORE SPECIFICALLY, MICROGLIAL ACTIVATION
IN MAJOR DEPRESSIVE EPISODES”
93
94. 94
… this finding is important for improving
treatment because it implies that therapeutics
known to reduce microglial activation
should be promising for depression …
(Setiawan et al. 2015)
95. THE SIGNIFICANCE OF GLIAL CELLS
AN INTERESTING ASIDE
WHEN EINSTEIN DIED IN 1955,
HIS BRAIN WAS PRESERVED IN A JAR OF FORMALDEHYDE
MOST PEOPLE EXPECTED THAT HIS BRAIN WOULD BE
LARGER THAN AVERAGE – BUT IT WAS NOT
THIRTY YEARS LATER, HOWEVER, SOMETHING DIFFERENT
ABOUT HIS BRAIN WAS DISCOVERED
EINSTEIN’S BRAIN HAD EXTRA GLIAL CELLS
ESPECIALLY IN THE ASSOCIATION CORTEX
THE BRAIN AREA INVOLVED WITH IMAGINATION AND COMPLEX THINKING
IT HAD LONG BEEN KNOWN THAT NEURONS
“SPOKE” ACROSS SYNAPSES
BUT NOW IT BECAME CLEAR THAT GLIA ALSO “TALKED”
NOT ONLY WITH ONE ANOTHER BUT ALSO WITH NEURONS
95
96. THE SIGNIFICANCE OF GLIAL CELLS
GLIA HAVE RECEPTORS FOR MANY OF THE SAME
CHEMICAL MESSENGERS USED BY NEURONS
WHICH ENABLES THEM TO “EAVESDROP” ON NEURONS AND
TO RESPOND IN WAYS THAT WILL FACILITATE NEUROTRANSMISSION
AND A CERTAIN VARIETY OF GLIA WRAPS ITSELF AROUND
NERVE AXONS TO FORM “INSULATING” MYELIN SHEATHS
THEREBY ACCELERATING TRANSMISSION SPEEDS 50 – FOLD
IN FACT, WHEN ANIMALS ARE RAISED IN LEARNING – RICH
ENVIRONMENTS, MYELINATION INCREASES
SUGGESTING THAT GLIA MAY ACTIVELY CONTRIBUTE TO LEARNING
GLIA ALSO CONTRIBUTE TO THE NORMAL APOPTOTIC
DESTRUCTION OF SYNAPSES DURING BRAIN DEVELOPMENT
UNNECESSARY CONNECTIONS ARE CONTINUOUSLY BEING CUT BACK
IN ORDER TO STREAMLINE THE NEURAL CIRCUITRY
BECAUSE OF THE CRITICAL ROLES PLAYED BY GLIA IN
NEUROTRANSMISSION AND NEURAL / SYNAPTIC PLASTICITY,
IT IS NO SURPRISE THAT EINSTEIN HAD SO MANY OF THEM
96
97. THE “NEUROIMMUNE” COMPONENT OF DEPRESSION
BUT STRESS – INDUCED ABNORMAL GLIAL ACTIVITY
IS NOW BEING ASSOCIATED WITH NOT ONLY
DEPRESSION BUT ALSO SUCH DISORDERS AS
DYSLEXIA ~ AUTISM ~ STUTTERING
TONE DEAFNESS ~ CHRONIC PAIN
SLEEP DISORDERS ~ EVEN PATHOLOGICAL LYING
AND OVERZEALOUS “PRUNING”
OF HEALTHY SYNAPSES
BY ROBUSTLY ACTIVATED GLIA
MAY BE A FACTOR IN SUCH
NEURODEGENERATIVE DISORDERS
AS ALZHEIMER’S DISEASE
PARENTHETICALLY, BOTH ALZHEIMER’S AND CHRONIC DEPRESSION
ARE ASSOCIATED WITH DECREASED HIPPOCAMPAL VOLUME
PARTICULARLY ALARMING INASMUCH AS
THE HIPPOCAMPUS PLAYS SUCH AN IMPORTANT ROLE IN MEMORY
ESPECIALLY THE CONSOLIDATION OF INFORMATION
FROM SHORT – TERM TO LONG – TERM MEMORY 97
98. MOVING NOW TO
THE “NEUROENDOCRINE” COMPONENT OF DEPRESSION
IMPORTANTLY
EXPOSURE TO CHRONIC STRESS RESULTS IN
PROLONGED HYPERACTIVATION OF THE HPA AXIS,
WHICH LEADS TO INCREASED LEVELS OF CORTISOL
BUT THIS, IN TURN, EVENTUALLY CAUSES DOWNREGULATION
OR DESENSITIZATION
OF THE CORTISOL RECEPTORS IN
THE HYPOTHALAMUS AND THE PITUITARY
CONSEQUENTLY
INSTEAD OF A NEGATIVE FEEDBACK LOOP
DESIGNED TO RESTORE HOMEOSTASIS
BY RETURNING THE CORTISOL LEVELS TO NORMAL
ONCE THE DANGER HAS PASSED
A POSITIVE (AMPLIFYING) FEEDBACK LOOP WILL BE ESTABLISHED,
RESULTING IN EVER – INCREASING LEVELS OF CORTISOL
98
100. THE “ENDO – IMMUNE” COMPONENT OF DEPRESSION
FURTHERMORE AND EQUALLY SIGNIFICANTLY
THE EVER – INCREASING LEVELS OF CORTISOL
WILL ALSO CAUSE DOWNREGULATION
OF THE CORTISOL RECEPTORS ON BOTH
MACROPHAGES (PERIPHERALLY)
AND MICROGLIA (CENTRALLY)
THE NET RESULT OF WHICH
WILL BE DESENSITIZATION
OF THE IMMUNE SYSTEM
TO THE ANTI – INFLAMMATORY
AND IMMUNOSUPPRESSIVE
EFFECTS OF CORTISOL
100
101. THE “ENDO – IMMUNE” COMPONENT OF DEPRESSION
IN SUM
CHRONIC STRESS LEADS TO
A HYPERACTIVATED HPA AXIS,
CHRONICALLY ELEVATED
CORTISOL LEVELS,
CHRONICALLY DECREASED SENSITIVITY
OF THE IMMUNE CELLS TO CORTISOL,
AND CHRONIC FAILURE TO
INHIBIT INFLAMMATORY PROCESSES,
THEREBY EFFECTIVELY STIMULATING
INFLAMMATORY PROCESSES
RESULTING IN CHRONIC INFLAMMATION
101
102. 102
… these data provide support for a model suggesting that
prolonged exposure to stress results in cortisol resistance,
which in turn interferes with appropriate regulation of
inflammation … (Cohen et al. 2012)
103. 103
… reduced glucocorticoid signaling, as a result of
glucocorticoid resistance, creates a permissive
environment for an overactive innate immune system …
(Horowitz and Zunszain 2015)
104. EXTENSIVE CROSSTALK
NOT ONLY
DO ELEVATED LEVELS OF CORTISOL ULTIMATELY
INCREASE INFLAMMATION
THROUGH THEIR FAILURE TO DOWNREGULATE
THE INFLAMMATORY RESPONSE
AN INSTANCE OF THE ENDOCRINE SYSTEM’S
IMPACT ON THE IMMUNE SYSTEM
BUT ALSO
PRO – INFLAMMATORY CYTOKINES GIVE RISE TO
EVER – INCREASING LEVELS OF CORTISOL
THROUGH THEIR “POTENT ACTIVATION” OF THE HPA AXIS
AN INSTANCE OF THE IMMUNE SYSTEM’S
IMPACT ON THE ENDOCRINE SYSTEM
THE NET RESULT OF WHICH WILL BE TOTAL
DYSREGULATION OF THE IMMUNE SYSTEM
AND A RUNAWAY INFLAMMATORY CASCADE 104
105. 105
… some of the pro-inflammatory cytokines are
potent activators of the HPA axis …
(Leonard 2001)
106. IN SUM
IN AT LEAST A COHORT
OF VULNERABLE INDIVIDUALS
INFLAMMATION MAY INDEED
PLAY A MAJOR ROLE
IN THE ETIOLOGY OF DEPRESSION
ACTING NOT ONLY
AS A PRECIPITATING FACTOR
THAT PROPELS THE INDIVIDUAL INTO DEPRESSION
BUT ALSO AS A PERPETUATING FACTOR
THAT MAY POSE AN OBSTACLE TO RECOVERY
IN ESSENCE
WE ARE SPEAKING TO A PIVOTAL ROLE FOR
THE IMMUNE SYSTEM IN MODULATING AFFECT
106
107. SO THIS IS
MY PSYCHO –
SOCIO –
GENO –
ENVIRO –
GASTROENTERO –
NEURO –
IMMUNO –
ENDOCRINO –
LOGIC THEORY OF DEPRESSION
WHICH POSTULATES THAT STRESS – INDUCED
INFLAMMATION AND A DYSREGULATED MindBrain
RESULT FROM THE COMPLEX INTERDEPENDENCE OF
ANTECEDENT SENSITIZING FACTORS AND DYSFUNCTIONAL
REGULATORY SYSTEMS THROUGHOUT THE LIVING SYSTEM
(STARK 2016)
107
108. MY PSYCHO – SOCIO – GENO – ENVIRO – GASTROENTERO –
NEURO – IMMUNO – ENDOCRINO – LOGIC THEORY OF DEPRESSION
NEUROENDOCRINE DYSFUNCTION
NEUROIMMUNE ALTERATION
CAUSE INFLAMMATION
AND THEN DEPRESSION
BUT I HAVE A GOOD SOLUTION
ELIMINATE TOXICITY
AND REPLENISH DEFICIENCY
NOW YOU’LL BE LESS STRESSED
NO LONGER DEPRESSED
I HOPE YOU LIKE MY THEORY
(STARK 2016)
108
109. IMPLICATIONS FOR TREATMENT
TARGETED THERAPEUTIC REGIMENS
DESIGNED TO REDUCE INFLAMMATION
GIVEN THE DIRECT LINK BETWEEN INFLAMMATION
AND DEPRESSION IN AT LEAST A SUBSET OF PATIENTS,
IN ADDITION TO FERRETING OUT UNDERLYING CAUSES
FOR BOTH THE INFLAMMATION AND THE DEPRESSION
SEVERAL SIMPLE BLOOD TESTS
SHOULD BE ROUTINELY PERFORMED
ON ALL DEPRESSED PATIENTS
IN ORDER TO GET A “READ” ON THE
INFLAMMATORY STATUS OF THEIR BODY
AND THEN ANTI – INFLAMMATORY (NEUROPROTECTIVE)
SUPPLEMENTS AND ACTIVITIES CAN BE PRESCRIBED
AS EITHER REPLACEMENTS FOR OR ADJUNCTS TO WHATEVER
OTHER ANTIDEPRESSANT REGIMENS ARE ALREADY IN PLACE
109
110. BIOMARKERS OF SYSTEMIC INFLAMMATION
HIGH SENSITIVITY C – REACTIVE PROTEIN (hs – CRP)
CRP IS ONE OF A GROUP OF PROTEINS (“ACUTE – PHASE REACTANTS”)
PRODUCED BY THE LIVER AS PART OF THE IMMUNE SYSTEM’S
EARLY INFLAMMATORY RESPONSE TO HARMFUL STIMULI
hs – CRP IS THE BEST BIOMARKER OF
ACUTE INFLAMMATION IN BLOOD VESSELS
AT THE MICROVASCULAR LEVEL
PARTICULARLY RELEVANT FOR HEART AND BRAIN
IN FACT
hs – CRP IS A MORE ACCURATE AND SENSITIVE INDICATOR
OF THE ACUTE PHASE RESPONSE
THAN THE ERYTHROCYTE SEDIMENTATION RATE (ESR)
OPTIMAL hs – CRP BLOOD LEVELS
ARE < 1.0 MILLIGRAM PER LITER
HIGHER LEVELS SUGGEST SYSTEMIC INFLAMMATION
110
111. BIOMARKERS OF SYSTEMIC INFLAMMATION
HOMOCYSTEINE
AN INTERMEDIARY IN THE METHIONINE – HOMOCYSTEINE (METHYLATION) CYCLE
A TOXIC SULFUR – CONTAINING AMINO ACID THAT NEEDS TO BE
METHYLATED IN ORDER TO BE CONVERTED BACK TO METHIONINE
(AN ESSENTIAL AMINO ACID THAT PLAYS SEVERAL VITAL PHYSIOLOGICAL ROLES IN THE BODY)
ELEVATED LEVELS OF HOMOCYSTEINE ARE ASSOCIATED
WITH OXIDATIVE STRESS, FREE RADICAL DAMAGE,
DYSREGULATED NEUROTRANSMISSION, CHRONIC INFLAMMATION,
COGNITIVE DECLINE, AND DEPRESSION
SEVERAL RESEARCHERS HAVE EVEN ADVANCED
THE HOMOCYSTEINE THEORY OF DEPRESSION
(FOLSTEIN et al. 2007; MECH AND FARAH 2016)
COMMON SYMPTOMS OF WHICH INCLUDE
PERFECTIONISM, INTENSE COMPETITIVENESS, DRIVENNESS,
HIGH ACHIEVEMENT, OBSESSIVE – COMPULSIVE TRAITS,
ANXIETY, RITUALISTIC BEHAVIORS, AND ADDICTIVE TENDENCIES
OPTIMAL HOMOCYSTEINE BLOOD LEVELS
ARE < 6.0 MICROMOLES PER LITER 111
112. 112
… high homocysteine levels cause cerebrovascular
disease, neurotransmitter deficiency, and depression …
(Folstein et al. 2007)
113. BIOMARKERS OF SYSTEMIC INFLAMMATION
MORE SPECIFICALLY, ELEVATED LEVELS OF HOMOCYSTEINE
ARE OFTEN FOUND IN UNDERMETHYLATORS
UNDERMETHYLATION CAN BE THE RESULT OF EITHER GENETICS OR EPIGENETICS
METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR)
IS A COMMON GENETIC POLYMORPHISM
ASSOCIATED WITH UNDERMETHYLATION
BETWEEN 30% AND 60% OF THE POPULATION ARE UNDERMETHYLATORS
THE MTHFR ENZYME, ENCODED BY THE MTHFR GENE,
IS RESPONSIBLE FOR METHYLATING FOLATE
WITH THE ASSISTANCE OF VITAMIN B12 AS A COFACTOR
THIS “ACTIVATED” FORM OF FOLATE (METHYLFOLATE) CATALYZES
THE CONVERSION OF HOMOCYSTEINE BACK TO METHIONINE
(A POWERFUL ANTIOXIDANT)
BY DONATING ITS METHYL GROUP
THEREBY PREVENTING TOXIC BUILDUP OF HOMOCYSTEINE
IT IS EASY ENOUGH TO SUPPLEMENT A DEPRESSED PATIENT’S DIET
WITH THE ACTIVATED (METHYLATED) FORMS OF
VITAMIN B12 (METHYLCOBALAMIN) AND FOLATE (L – METHYLFOLATE)
113
115. BIOMARKERS OF SYSTEMIC INFLAMMATION
VITAMIN D BLOOD LEVEL
PROVIDES AN INDIRECT MEASUREMENT
OF THE BODY’S INFLAMMATORY STATUS
THE LOWER THE VITAMIN D LEVEL,
THE HIGHER THE DEGREE OF INFLAMMATION
INSULIN BLOOD LEVEL
CAN BE USED NOT ONLY TO SCREEN FOR DIABETES
BUT ALSO AS A ROUGH MARKER FOR INFLAMMATION
THE HIGHER THE FASTING INSULIN LEVEL,
THE HIGHER THE DEGREE OF INFLAMMATION
IMMUNOASSAYS TO DETECT CYTOKINE LEVELS
ALTHOUGH STILL QUITE PRICEY
ARE BECOMING AN INCREASINGLY POPULAR WAY
TO QUANTIFY CYTOKINES IN THE BLOOD
115
116. ANTI – INFLAMMATORY
TREATMENT OPTIONS
THE MOST EFFECTIVE WAY
TO COMBAT
CHRONIC INFLAMMATION
IS THROUGH
EXERCISE AND DIET
116
117. REGULAR PHYSICAL EXERCISE TO
ALLEVIATE SYMPTOMS OF DEPRESSION
BOTH AEROBIC TRAINING
(ENDURANCE TRAINING)
AND STRENGTH TRAINING
(MUSCLE CONTRACTION AGAINST RESISTANCE)
WHEREAS BOUTS OF EXERCISE INCREASE ACUTE INFLAMMATION,
WHEN DONE REGULARLY OVER THE LONG TERM,
EXERCISE DECREASES CHRONIC INFLAMMATION
EXERCISE STIMULATES THE PRODUCTION
OF ANTI – INFLAMMATORY CYTOKINES
EXERCISE ALSO ENHANCES THE PRODUCTION
OF ENDORPHINS
“ENDOGENOUS MORPHINE” ~ ENDOGENOUS OPIOID NEUROPEPTIDES
WHICH INHIBIT THE TRANSMISSION OF PAIN SIGNALS
AND PRODUCE A FEELING OF EUPHORIA
SIMILAR TO THAT PRODUCED BY OTHER OPIOIDS
117
118. 118
… recent findings confirm that physical activity
induces an increase in the systemic levels of
a number of anti-inflammatory cytokines …
(Pinto et al. 2012)
119. PARENTHETICALLY
EXERCISE ALSO INCREASES THE PRODUCTION OF
BRAIN – DERIVED NEUROTROPHIC FACTOR (BDNF)
“TROPHIC” MEANS “GROWTH – PROMOTING”
“MIRACLE – GRO FOR THE BRAIN” (RATEY 2013)
BDNF IS A GROWTH FACTOR
ASSOCIATED WITH COGNITIVE IMPROVEMENT
IT PROMOTES NEUROGENESIS AND SYNAPTIC PLASTICITY
IN SPECIFIC AREAS OF THE BRAIN
MOST NOTABLY THE HIPPOCAMPUS
STRESS IS KNOWN TO DECREASE BDNF LEVELS
THE NEUROTROPHIC THEORY OF DEPRESSION
IMPLICATES REDUCED LEVELS OF BDNF,
ATROPHY OF STRESS – VULNERABLE HIPPOCAMPAL NEURONS,
AND DECREASED HIPPOCAMPAL VOLUME
IN THE PATHOGENESIS OF DEPRESSION
CORROBORATED BY THE FINDING THAT ANTIDEPRESSANTS APPEAR TO
INCREASE BDNF LEVELS, REVERSE ATROPHY OF HIPPOCAMPAL NEURONS,
AND INCREASE HIPPOCAMPAL VOLUME
(DUMAN et al. 1997) 119
120. 120
… stress can decrease the expression of BDNF and lead to
atrophy of stress-vulnerable hippocampal neurons …
… the possibility that the decreased size and impaired
function of these neurons may be involved in depression
is supported by recent clinical imaging studies …
(Duman et al. 1997)
121. ELIMINATE PRO – INFLAMMATORY FOODS
PRO – INFLAMMATORY CYTOKINES
ARE PRODUCED BY AN UNHEALTHY DIET
SUGAR AND HIGH FRUCTOSE CORN SYRUP,
REFINED GRAINS, PROCESSED FOODS, AND TRANS FATS
AVOID THE NIGHTSHADES
POTATOES, TOMATOES, PEPPERS, AND EGGPLANT
EAT AN ANTI – INFLAMMATORY DIET
WHOLE, UNPROCESSED, ORGANIC “REAL” FOOD
FERMENTED FOODS (KEFIR, MISO, PICKLES, OLIVES, SAUERKRAUT)
PROBIOTICS (INCLUDING RAW YOGURT)
TO “RESEED” THE GUT WITH BENEFICIAL BACTERIA
HIGH – QUALITY, ANTI – INFLAMMATORY HERBS AND SPICES
HIGH – QUALITY, UNPROCESSED FATS
121
122. TURMERIC
THE SPICE THAT GIVES CURRY ITS YELLOW COLOR
ONE OF THE MOST THOROUGHLY RESEARCHED PLANTS ON THE PLANET
ITS PROFOUND HEALING ABILITIES CAN BE TRACED
TO ITS POWERFUL ANTI – INFLAMMATORY ACTION
IT IS ALSO A VERY STRONG ANTIOXIDANT
TAKE A FULL – SPECTRUM TURMERIC EXTRACT
(AS OPPOSED TO AN ISOLATED CURCUMIN EXTRACT)
AND ONE THAT IS “LIPOSOMALIZED”
LIPOSOMES ARE USED AS VEHICLES FOR ADMINISTRATION
OF NUTRIENTS AND PHARMACEUTICAL DRUGS
THAT MIGHT OTHERWISE BE HARD FOR THE BODY TO ABSORB
LIPOSOMALIZATION INVOLVES ENCAPSULATING
THE TURMERIC EXTRACT IN A PHOSPHOLIPID BILAYER
IN ORDER TO INCREASE ITS BIOAVAILABILITY
122
123. OMEGA – 3 FATTY ACIDS
POLYUNSATURATED FATTY ACIDS (PUFAs)
EICOSAPENTAENOIC ACID (EPA) AND DOCOSAHEXAENOIC ACID (DHA)
A 2012 GROUNDBREAKING STUDY CONDUCTED AT THE
UNIVERSITY OF CALIFORNIA (SAN DIEGO) UNCOVERED A CLASS
OF “SPECIALIZED” INFLAMMATION – REGULATING MOLECULES
THAT ARE PRODUCED INSIDE THE BODY’S TISSUES
FROM THE OMEGA – 3 FATTY ACIDS FOUND IN FISH OIL
THESE “PRO – RESOLUTION MOLECULES”
(LIPOXINS, RESOLVINS, AND PROTECTINS)
STIMULATE ACTIVE RESOLUTION OF INFLAMMATION
(NORRIS AND DENNIS 2012)
SUPPLEMENTING WITH 2 – 3 GRAMS PER DAY OF
OMEGA – 3 FATTY ACIDS FROM A HIGH – QUALITY
FISH OIL WILL BOOST PRODUCTION OF THESE
ENDOGENOUS CHEMICAL MEDIATORS, THEREBY
SERVING TO “RESOLVE AND PROTECT AGAINST”
INFLAMMATORY CONDITIONS
123
124. BUT A WORD OF CAUTION
ALWAYS TAKE THE FAT – SOLUBLE ANTIOXIDANT VITAMIN E
ALONG WITH THE ANTI – INFLAMMATORY EPA AND DHA
POLYUNSATURATED FATTY ACIDS (PUFAs)
(LIKE EPA AND DHA – TWO OF THE MOST IMPORTANT OMEGA – 3s)
ARE LIPIDS WITH TWO OR MORE CARBON – CARBON DOUBLE BONDS
THE GREATER THE DEGREE OF UNSATURATION
(THAT IS, THE GREATER THE NUMBER OF DOUBLE BONDS IN ITS HYDROCARBON CHAIN),
THE MORE “FRAGILE” IT IS AND THE MORE EASILY IT CAN BE “OXIDIZED”
(THAT IS, HAVE ITS ELECTRONS STOLEN)
BY “FREE RADICALS” IN SEARCH OF ELECTRONS
TO RESTORE THEIR ELECTRON BALANCE
REMOVAL OF ELECTRONS FROM THE FATTY ACID
(THAT IS, “OXIDATIVE DEGRADATION OF THE FATTY ACID” OR “LIPID PEROXIDATION”)
WILL CONVERT IT INTO A TOXIC “REACTIVE OXYGEN SPECIES” (ROS)
(THAT IS, IT WILL ITSELF BECOME A “FREE RADICAL” OR “OXIDANT”)
NOW “OXIDIZED” AND A “FREE RADICAL,” THE FATTY ACID
WILL WREAK HAVOC THROUGHOUT THE BODY BY CAUSING
“OXIDATIVE DAMAGE” (“OXIDATIVE STRESS”) TO MEMBRANES, PROTEINS,
AND CELLULAR DNA AS IT SCAVENGES FOR ELECTRONS TO COMPLETE ITSELF
THUS THE IMPORTANCE OF TAKING EPA AND DHA WITH VITAMIN E
(AN “ANTIOXIDANT” THAT WILL SLOW OR EVEN PREVENT THE “OXIDATIVE PROCESS”)
124
125. NOVEL TREATMENT APPROACHES FOR HARD – TO – TREAT DEPRESSIONS
BOTULINUM TOXIN
A DRAMATIC ILLUSTRATION OF THE
HORMETIC (BIPHASIC) DOSE – RESPONSE
IN HIGH DOSES,
BOTULINUM IS NEUROTOXIC
IT IS THE MOST POISONOUS BIOLOGICAL AGENT KNOWN
BUT IN LOWER DOSES,
BOTULINUM IS ANTI – INFLAMMATORY
AND USED FOR TEMPORARY ERASING
OF FROWN LINES AND CROW’S FEET
“IF YOU CAN’T FROWN, YOU WON’T BE SO SAD”
A SINGLE INJECTION INTO THE FACIAL “FROWN MUSCLES”
CAN PROVIDE LASTING RELIEF FROM DEPRESSION
(FINZI AND ROSENTHAL 2014)
125
126. 126
… a single treatment with onabotulinumtoxinA (OBA)
<injected into frown muscles> appears to induce a
significant and sustained antidepressant effect
in patients with major depression …
(Finzi and Rosenthal 2014)
127. NOVEL TREATMENT APPROACHES FOR HARD – TO – TREAT DEPRESSIONS
SMILING
“IF YOU SMILE MORE, YOU WON’T BE SO SAD”
FAKE IT UNTIL YOU MAKE IT
SMILING IS A POWERFUL IMMUNE BOOSTER
AND MOOD STABILIZER
STUDIES HAVE SHOWN THAT SMILING
RELEASES ENDORPHINS AND SEROTONIN
“SMILING IS A WAY OF TRICKING YOUR BRAIN
INTO THINKING THAT EVERYTHING’S OK,
EVEN IF IT’S NOT”
(PLANT AND STEPHENSON 2011)
127
128. WHO KNEW ?!?
ANTIDEPRESSANTS THEMSELVES
ARE ANTI – INFLAMMATORY
THE PRIMARY MECHANISM OF ACTION
OF ANTIDEPRESSANTS
HAD LONG BEEN THOUGHT
TO INVOLVE CORRECTING
CHEMICAL IMBALANCES IN THE BRAIN
ONLY MORE RECENTLY, HOWEVER,
HAS IT BECOME APPARENT THAT
ANTIDEPRESSANTS ALSO EXERT
ANTI – INFLAMMATORY EFFECTS
WHICH MIGHT BE RESPONSIBLE, AT LEAST IN PART,
FOR THE SEVERAL – WEEK DELAY IN ACTION (“LATENCY PERIOD”)
THAT CHARACTERIZES MOST ANTIDEPRESSANTS
128
129. 129
… studies have demonstrated that antidepressants can
inhibit the production and/or release of pro-inflammatory
cytokines and stimulate the production of anti-
inflammatory cytokines, suggesting that reduction in
inflammation might contribute to treatment response …
(DeBerardis et al. 2010)
130. 130
… these findings suggest that antidepressants may
owe at least some of their therapeutic effectiveness
to their anti-inflammatory properties …
(Tynan et al. 2012)
131. I CONCLUDE WITH MY FINAL LIMERICK …
NEUROINFLAMMATION
AND DEPRESSION
TO HEAL DISORDER AND DISEASE
TRY ANTI – INFLAMMATORIES
BUT FIRST YOU ADDRESS
UNDERLYING STRESS
AND THEN PRESCRIBE OMEGA – 3s
(STARK 2016)
131
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Editor's Notes
… a link between chronic inflammation and dementia, at least in some patients with recurrent and chronic depression … (Leonard 2017)
(R Dantzer et al. 2008)
bipolar patients on high-dose lithium carbonate
(e.g., 900 – 1,200 mg / day) have been found to have
a reduced incidence of Alzheimer’s disease, which
has led researchers to hypothesize that lithium (at either
its standard dose or in trace amounts) is powerfully
anti-inflammatory and neuroprotective
… cognitive benefits for dementia prevention …
so even low – dose lithium orotate (e.g., 5 mg / day)
may have “cognitive benefits for dementia prevention”
(Mauer et al. 2014)
PAST EXPERIENCE BECOMES THE FILTER THROUGH WHICH WE EXPERIENCE THE WORLD
what are the words appearing in the red triangles –
if you think they say “Once upon a time,” and “A shot in the dark,” think again!
the brain is a “prediction machine” – prior learning prompts us to see the world as we expect it to be, not as it really is
once a schema is in place and the cues around us look right enough, we are blind to details and context – we automatically process information as we expect it to appear, without investing any mental effort
… admittedly one who pretty much flies under the radar …
ketotic – using fat for energy
It depends on the unique genetic make-up and environment of each individual
… deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression …
…reciprocal interactions between inflammation, microbiota, and depression …
(Meyrel et al. 2017)
It depends on the unique genetic make-up and environment of each individual