Pain is not all in your head.



Categories Filed Under

  • painfully obvious yet—it seems—painfully obvious to only a small minority (of earthling humans).
  • true dat, EVAN IF you’re an Enlightened One, a Holiest of the Holy, an Ultimate-Reality-Know-er , or a Malignant Psychopath.



what we think we know about stress: part three

Part 3: 

Leptin’s Multifaceted Role in the Human Stress Response  :-)

But first, to recap:

  • Part Two highlights current research and biomedical perspectives on acute stress; chronic stress; traumatic stress; stress and sleep; stress and endogenous dopamine; stress and neurological disorders; and, finally—physiological stress responses embedded in social relationships and within socioepolitical contexts.

  • Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland: leptin inhibits cortisol release directly (1997) Bornstein et al.  The impact of  glucocorticoids (and the functions of leptin) on the hypothalamic-pituitary-adrenal (HPA) axis indicates a crucial “interaction of leptin with the glucocorticoid system.” Hence this study tested leptin’s effects on adrenalcortical steroidogenisis. in addition to “the effects of leptin on basal and ACTH-stimulated cortisol secretion” The research results showed “leptin inhibits cortisol production in adrenocortical cells and therefore appears to be a metabolic signal that directly acts on the adrenal gland.” (emphasis mine)
  • Leptin down-regulates the steroid producing system in the adrenal (1998) Kruse, et al.  “Leptin inhibits the secretion of cortisol in primary cultures of bovine adrenocortical cells…To analyze if leptin regulates other major enzymes involved in adrenal steroidogenesis we tested its effect on mRNA expression for two further key enzymes…” Study results showed that “leptin reduces cortisol synthesis in the adrenal by down-regulating the steroid producing enzyme cascade in the cortical cell.” (emphasis mine)
  • Leptin and the adrenal gland (2000) Glasow & Bornstein. “Via its receptor in the hypothalamus, leptin modulates the functioning of the hypothalamic-pituitary-adrenal axis and the systemic sympathetic/ adrenomedullary system,…In regard of potential interactions of leptin and adrenal hormones this study intended to characterize the role of leptin in the human adrenal gland….Our data demonstrate that leptin can regulate the human adrenal function directly, via its receptors on adrenocortical cells. Leptin decreased the corticotropin-stimulated release of steroid hormones in vitro without any effect on cell proliferation…This adipo-adrenal interaction mediated by leptin further underscores the close link of metabolism and stress regulation in humans.” (emphasis mine)
  • Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery (2001). Modan-Moses, et al. “Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters… CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol…” (emphasis mine)
  • Leptin: Metabolic control and regulation (2002) Sandoval & Davis.  Leptin’s response to stress (other than stress from decreased energy consumption) has often seemed unclear or inconclusive. For example, “with hypoglycemia stress, the literature may conflict because experimentally hypoglycemia is induced with infusion of insulin, an endocrine factor that can increase leptin levels. With exercise, leptin’s response may depend on duration and intensity of exercise. While it has been clearly shown that the sympathetic nervous system (SNS) inhibits leptin secretion in a variety of experimental modes, the hypothalamic – pituitary –adrenal (HPA) axis may stimulate leptin secretion. This creates a paradox of leptin regulation during stress since both systems are activated with stress. If the SNS inhibition overrides the HPA axis’ activation of leptin secretion, leptin’s role during stress may be to allow a shifting of fuel consumption towards carbohydrate utilization. In type 1 diabetes mellitus, autonomic dysfunction may prevent the fall in leptin during stress. Although obesity is associated with type 2 diabetes mellitus, patients may have decreased leptin levels, especially when glucose is poorly controlled….The purpose of this review to is critically analyze the literature regarding the impact of different types of stress on leptin secretion, the function of leptin during stress, and the role of leptin in the pathophysiology of diabetes.” (emphasis mine)
  • Leptin as an acute stress-related hormone in the fetoplacental circulation. (2002) Y Takahashi, et al. “…Evidence shows that leptin’s fetoplacental circulation is independent of its maternal circulation…In adult humans, leptin is discussed as a stress‐related hormone.… Hypercapnia of the umbilical cord, monitored as fetal distress...correlated with leptin level, suggesting that leptin may be associated with acute stress. In adult humans, a significant correlation was reported between baseline levels of leptin and body mass index 3 days before cholecystectomy, but on the third postoperative day, there were significant increases in the serum levels of cortisol, free fatty acids, leptin, and C‐reactive protein, suggesting that there may be two biological implications of leptin secretion in body mass index and surgical stress. In the fetoplacental circulation, respiratory acidosis, which is one stress‐related factor, may induce leptin secretion. Umbilical cord erythropoietin as an adaptation factor for hypoxia is also associated with cord blood leptin in mothers with insulin‐dependent diabetes mellitus. Intrauterine growth restriction infants show an increased leptin level in the umbilical cord…demonstrating conflicting roles for leptin secretion...In conclusion, although the pathophysiology of leptin secretion in the fetoplacental circulation is complicated and leptin secretion seemingly has contradictory functions, it seems likely that leptin may have two important roles: one as an acute stress‐related hormone, and the other for fetal fat mass control…” (emphasis mine)
  • Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin (2004). Spiegel, et al.  “The present study tests the hypothesis that circulating levels of leptin…are influenced by sleep duration. We also analyzed associations between leptin and sympathovagal balance, cortisol, TSH, glucose, and insulin under different bedtime conditions…The effects of sleep duration on leptin were quantitatively associated with alterations of the cortisol and TSH profiles…Measures of perceived stress were not increased during sleep restriction. During the study with 8-h bedtimes, hormonal and metabolic parameters were intermediate between those observed with 4-h and 12-h bedtimes. In conclusion, sleep modulates a major component of the neuroendocrine control of [leptin].” (emphasis mine)
  • Circulating leptin and stress-induced cardiovascular activity in humans. (2008) Brydon. et al. “We investigated the relationship between circulating leptin and cardiovascular and inflammatory responses to acute psychological stress in humans...In women only, baseline plasma leptin was significantly associated with stress-induced changes in heart rate…in heart rate variability…and in cardiac preejection period…independent of age, adiposity, and smoking. Women’s plasma leptin levels also correlated with stress-induced elevations in the proinflammatory cytokine interleukin-6…Circulating leptin is an independent predictor of sympathetic cardiovascular activity, parasympathetic withdrawal, and inflammatory responses to stress in women. Because cardiovascular and inflammatory stress responses are predictive of future cardiovascular disease, leptin may be a mechanism mediating the adverse effects of stress and obesity on women’s cardiovascular health.” (emphasis mine)
  • Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release. (2010) Malcher-Lopes, et al. “…Here we demonstrate a crosstalk between GC- and leptin-activated signaling pathways that rapidly controls endocannabinoid biosynthesis and release…involved in the regulation of…and the adaptation to stress. [L]eptin…provides the cellular mechanism for a central leptin-mediated regulation of major neuroendocrine axis and therefore represents an endocannabinoid-mediated…mechanism to coordinate the hormonal control of energy homeostasis, fluid balance, cardiovascular regulation, and the stress response. Sustained elevated circulating levels of GCs (e.g., by chronic stress, depression, or in Cushing’s syndrome) or leptin (e.g., in obesity) or GC deficiency (e.g., in Addison’s disease) could result in deregulation of this mechanism, leading to the eating, metabolic, and cardiovascular disorders associated with these pathological conditions.” (emphasis mine)
  • The link between stress and feeding behaviour. (2012) Maniam & Morris. “Exposure to stress is inevitable…throughout the lifespan. The impact of stress experienced in later life has been well documented …The effects of stress early in life are less well known…One of the major impacts of stress besides changes in psychosocial behaviour is altered feeding responses. The system that regulates stress responses, the hypothalamo-pituitary-adrenal axis, also regulates feeding responses…In other words the systems that control food intake and stress responses share the same anatomy and thus each system can influence each other in eliciting a response. Stress is known to alter feeding responses in a bidirectional pattern, with both increases and decreases in intake observed. Stress-induced bidirectional feeding responses underline the complex mechanisms and multiple contributing factors, including…peripheral signals   (leptin, insulin and ghrelin). This review discusses the neuropeptides that regulate feeding behaviour and how their function can be altered through cross-talk with hormones and neuropeptides that also regulate the hypothalamo-pituitary-adrenal axis. In addition, long-term stress induced alterations…and changes in gene expression of neuropeptides regulating stress…will be discussed.” (emphasis mine)
  • Leptin regulates dopamine responses to sustained stress in humans (2012) “Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment…Leptin is known to influence endocrine response to stress …This suggests that leptin…is important for motivational drives [and] may be additionally influenced by stress….This study directly links the leptin system with central dopaminergic function in the context of a universal stressor, moderate levels of sustained pain, in humans. Our results show that…leptin serves as a regulator of mesolimbic dopamine system during stressful, salient aversive states…Multiple brain regions are involved in assessing saliency and the emotional value of environmental stimuli that predict reward or threat… Taken together, this suggests that stress interacts with the leptin system’s ability to modulate the dopaminergic response to salient cues…Further, effective leptin signaling to central dopaminergic systems may facilitate an individual’s ability to attend to other salient cues (e.g. threat, stress, mating opportunities) en lieu of salient food-related cues…Effective leptin signaling to the central dopaminergic systems may influence an individual’s ability to attend to other salient cues which appears to be influenced by biological changes secondary to disease and stress…Future examination of these processes…appears warranted, given the role of the dopaminergic system in a number of pathological states that involve a dysregulation of motivated behavior, such as substance use, eating and mood disorders.” (emphasis mine)
  • Adipokines during early abstinence of crack cocaine in dependent women reporting childhood maltreatment. (2013) Levandowski, et al. “Childhood maltreatment has been associated with addiction and immune dysregulation…The aim of the study was to compare plasma levels of adipokines [e.g. leptin] during early abstinence in crack cocaine dependent women with (CM+) and without history of childhood maltreatment (CM-). One hundred four crack cocaine female users were followed for 20 days in a detoxification inpatient treatment unit…All crack users increased leptin plasma levels during early abstinence…Crack users reporting childhood maltreatment exhibited a significant reduction in plasma levels of adiponectin and resistin when compared to CM- group…This is the first study evaluating adipokines during crack cocaine abstinence. Our results suggest a modulator effect of childhood maltreatment on inflammatory status in treatment-seeking crack cocaine dependents during early abstinence.” (emphasis mine)
  • Metabolic syndrome–from the neurotrophic hypothesis to a theory (2013). Hristova MG.  “Metabolic syndrome (MetS) is a complex and heterogeneous disease characterized by central obesity, impaired glucose metabolism, dyslipidemia, arterial hypertension, insulin resistance and high-sensitivity C-reactive protein. In 2006, a…hypothesis considered the neurotrophins a key factor in MetS development. Chronic inflammatory and/or psychoemotional distress provoke a series of neuroimmunoendocrine interactions…An early and a late clinical stage in the course of MetS are defined….The important role of two neurotrophic factors…and, especially, of leptin for the development of MetS, obesity and type 2 diabetes mellitus is illustrated… A special attention is paid to the activity of the hypothalamo-pituitary-adrenal axis after stress. The application of the neurotrophic theory of MetS could contribute to the etiological diagnosis and individualized management of MetS by eliminating the chronic distress…and consequent pathology.” (emphasis mine)
  • Leptin influence in craving and relapse of alcoholics and smokers (2013) Aguiar-Nemer; Toffolo; da Silva; Laranjeira & Silva-Fonseca.  “Leptin inhibits signaling of dopamine in the nucleus accumbens, suggesting its role in regulating stress…The aim of this study was to review of the literature on the influence of leptin in the craving for alcohol and tobacco and whether there is already evidence that leptin may be a biomarker to indicate risk for craving and relapse…Only 12 articles were met the inclusion criteria, relating leptin with craving in alcoholics (n = 10) and smokers (n = 2)….Leptin levels increase during abstinence and this may be related to a reduction of dopaminergic action in mesolimbic system, resulting in a greater intensity of craving and maintenance of addictive behavior. Although there are few studies, the most recent results indicate the usefulness of leptin as a marker of risk for relapse among smokers and alcoholics in abstinence.” (emphasis mine)
  • Neuroendocrine Circuits Governing Energy Balance and Stress Regulation: Functional Overlap and Therapeutic Implications (2014)  Karen K Ryan & Yvonne M Ulrich-Lai.   SUMMARY: “Significant comorbidities between obesity-related metabolic disease and stress-related psychological disorders suggest important functional interactions between energy balance and brain stress integration. Largely overlapping neural circuits control these systems, and this anatomical arrangement optimizes opportunities for mutual influence. Here we first review the current literature identifying effects of metabolic neuroendocrine signals on stress regulation, and vice versa. Next, the contributions of reward-driven food intake to these metabolic and stress interactions are discussed. Lastly, we consider the interrelationships between metabolism, stress, and reward in light of their important implications in the development of therapies for metabolism- or stress-related disease.”

And THAT’s just a teeny-weeny-tiny sample of leptin’s accomplishments. You can explore a few hundred more of leptin’s charms—scattered around my blog—if you look here, here, here, and/or here.

Leptin, apparently, does not discriminate. (Unlike…ahem…never mind.)

In other words, leptin interacts with (i.e. alters and/or is altered by) stress responses of  practically any kind, and perhaps almost any intensity—given the wide ranging brain-territory covered by various leptin receptors (as more than one researcher has noted.)

I particularly appreciate the study suggesting a woman’s adiposity (typically HYPERleptinemic compared to a man’s) may perhaps demonstrate a protective cardiovascular capacity compared to that of a man (whose circulating leptin quantity by about (his) middle age is typically a mere one-third of the leptin volume sported by his female counterpart, kilo for kilo .)

However, my ABSOLUTE FAVORITE journal article about Leptin and Stress Adaptation is the finely crafted piece (in the above list) shown in last place: Neuroendocrine Circuits Governing Energy Balance and Stress Regulation: Functional Overlap and Therapeutic Implications (2014) written by Karen K Ryan & Yvonne M Ulrich-Lai.  The final phrase in their abstract makes my heart sing. (Seriously.) They GET it…apparently…for they refer to “stress-related disease,” as if describing ACTUAL AND PROFOUNDLY WORRISOME CONDITIONS for which helpful “therapies” have not yet been discovered or articulated.

Oh. Wait. By golly, now here’s an ingenious therapy just waiting to hit pharmacy shelves around the globe. Any. Decade. Now.


Stress, adaptation, and health disparities associated with status quo socioeconomic conditions and oppressive norms (e.g. poverty, stigma, racism.) Hey, this stuff is truly fascinating. Trust me. :-)

I’m going somewhere with all this….research…I think…

So, patience please?…..Or, you could simply wait a couple days—by then I’m bound to churn out another *poem.* Theoretically, it could even be a poem about something HAPPY!  :-)


what’s next

i don’t know what’s next (does anyone?)

perhaps it’s better this way

WTFD has me by the balls

no real relief in sight for the moment

i guess i had to get convinced

beyond any doubt

WTFD isn’t all in my noggin

isn’t mine to manage or control

hence all my research and reading about stress and trauma

long term consequences

irreversible damage

yadda yadda


i didn’t want to believe

i’m deteriorating physiologically

so fucking fast

multiple systems are not failing 100%

they simply cannot keep up with this insane pace

this zero mph pace that finds me huddled in the same spot

hour after hour day after day week after week

and so on and so forth

(with very rare and brief interludes of pseudo sleep)


i’ve never quite known what this expression meant

to burst into tears over nothing

until the past year

now it pains me to confess

most days that’s my biggest accomplishment


for hours i howl and howl in agony as if i’ve suddenly been informed

the love of my life was just found tortured to death

it’s feels  that intense and painful


so i guess i’m psychotic now

probably not by-the-book-psychotic




i have a bottle of anti-psych meds

so i suppose i can guess what’s next


tried them a few months ago in an emergency


discovered that

(even when taken in supposedly-sub-therapeutic doses)

they left me with a sliver of cognitive function

completely numb


without emotion without desire

without love


also  i gained 20 pounds in 10 days without even trying

(onset of diabetes = typical reaction for many users)

oh i don’t give a shit about my appearance


so that part is not upsetting


the upsetting part is facing the fact

this is the best available solution

even though it’s no solution at all except


the data suggests

i’m slightly less likely to do something

rash and irreversible


that is Big Modern Medicine’s best option for me

in 2014

in my country



it is the best LEGAL option that my money can buy

and yet


(lest i forget)

i am the crazy one


what we think we know about stress: part two


In Part One (posted on July 13, 2014) I quoted several relevant stress definitions (e.g. acute, chronic, toxic, traumatic) and provided research summaries about the consequences of Early Life Stress.

Part Two (posted right below) provides summaries of research/theory about acute stress; chronic stress; traumatic stress; stress and sleep; stress and endogenous dopamine; stress and neurological disorders; and stress responses embedded within social relationships and sociopolitical contexts.

Stress and disorders of the stress system (2009) ”Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is re-established by various physiological and behavioral adaptive responses…The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic hormones…and autonomic norepinephrine centers in the brainstem. Targets of these effectors include the executive and/or cognitive, reward and fear systems, the wake-sleep centers of the brain, the growth, reproductive and thyroid hormone axes, and the gastrointestinal, cardiorespiratory, metabolic, and immune systems. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions…” (emphasis mine)

  • Leptin regulates dopamine responses to sustained stress in humans (2012) “Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment…Leptin is known to influence endocrine response to stress and alter stress-induced food consumption. This suggests that leptin…is important for motivational drives [and] may be additionally influenced by stress….This study directly links the leptin system with central dopaminergic function in the context of a universal stressor, moderate levels of sustained pain, in humans. Our results show that…leptin serves as a regulator of mesolimbic dopamine system during stressful, salient aversive states…Multiple brain regions are involved in assessing saliency and the emotional value of environmental stimuli that predict reward or threat… Taken together, this suggests that stress interacts with the leptin system’s ability to modulate the dopaminergic response to salient cues…Further, effective leptin signaling to central dopaminergic systems may facilitate an individual’s ability to attend to other salient cues (e.g. threat, stress, mating opportunities) en lieu of salient food-related cues…Effective leptin signaling to the central dopaminergic systems may influence an individual’s ability to attend to other salient cues which appears to be influenced by biological changes secondary to disease and stress…Future examination of these processes…appears warranted, given the role of the dopaminergic system in a number of pathological states that involve a dysregulation of motivated behavior, such as substance use, eating and mood disorders.” (emphasis mine)

Vulnerability to stroke: implications of perinatal programming of the hypothalamic-pituitary-adrenal axis (2009) “Chronic stress is capable of exacerbating each major, modifiable, endogenous risk factor for cerebrovascular and cardiovascular disease. Indeed, exposure to stress can increase both the incidence and severity of stroke, presumably through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Now that characterization of the mechanisms underlying epigenetic programming of the HPA axis is well underway, there has been renewed interest in examining the role of early environment on the evolution of health conditions across the entire lifespan. Indeed, neonatal manipulations in rodents that reduce stress responsivity, and subsequent life-time exposure to glucocorticoids, are associated with a reduction in the development of neuroendocrine, neuroanatomical, and cognitive dysfunctions that typically progress with age. Although improved day to day regulation of the HPA axis also may be accompanied by a decrease in stroke risk, evidence from rodent studies suggest that an associated cost could be increased susceptibility to inflammation and neuronal death in the event that a stroke does occur and the individual is exposed to persistently elevated corticosteroids. Given its importance in regulation of health and disease states, any long-term modulation of the HPA axis is likely to be associated with both benefits and potential risks…” (emphasis mine)

Shame: an acute stress response to interpersonal traumatization (2013) “This paper conceptualizes shame as an acute stress response to an unacceptable view of oneself mediated through another’s perspective…the author first illustrates how shame may induce a depressive paralysis and self-hurtful intent when the goal of reconciliation is thwarted. She then addresses how shame ignited by narcissistic injury can mobilize aggressive behavior toward others, motivated by a need to restore the self. The goals of this paper are to demonstrate that the configurations of shame are manifestations of interpersonal traumatization, to define them as predictable stress responses…and to propose the use of these conceptualizations in the empirical study of interpersonal traumatization.” (emphasis mine)

Acute stress response and posttraumatic stress disorder in traffic accident victims: a one-year prospective, follow-up study (1999) “This study was designed to assess the natural course of posttraumatic symptoms formation, as well as the degree to which acute stress reactions predict later posttraumatic stress disorder (PTSD) in injured traffic accident victims….In this study, a significant portion of injured traffic accident victims manifested PTSD 1 year after the event. The development of PTSD at 1 year can be predicted as early as 1 week after the accident on the basis of the existence and severity of early PTSD-related symptoms. However, the first 3 months following the accident appear to be the critical period for the development of PTSD.” (emphasis mine)

Chronic Stress Induces Impairment of Spatial Working Memory Because of Prefrontal Dopaminergic Dysfunction (2000)Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment…Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress…induces a organic disorder such as hippocampal neuronal degeneration…These [current] results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC….” (emphasis mine) 

Chronic stress causes frontostriatal reorganization and affects decision-making (2009) “The ability to shift between different behavioral strategies is necessary for appropriate decision-making. Here, we show that chronic stress biases decision-making strategies, affecting the ability…to perform actions on the basis of their consequences…in making choices, rats subjected to chronic stress became insensitive to changes in outcome value and resistant to changes in action-outcome contingency. Furthermore, chronic stress caused opposing structural changes in…corticostriatal circuits underlying these different behavioral strategies, with atrophy of medial prefrontal cortex…and hypertrophy of the sensorimotor striatum. These data suggest that…chronic stress leads to a bias in behavioral strategies toward habit.” (emphasis mine)

Can stress trigger Parkinson’s disease? (2014) “Can emotional stress trigger Parkinson’s disease (PD)? This idea is compelling but not new. More than 100 years ago, Gowers wrote that prolonged anxiety and emotional shock are ‘the most common antecedents of Parkinson’s disease’ and advised his patients to refrain from ‘all causes of mental strain and of physical exhaustion’. Extreme psychological stress, such as the holocaust, has been associated with PD and in some studies ex-prisoners of war had a significantly higher incidence of developing PD several decades after their release…Chronic stress…causes a prolonged activation of the hypothalamic–pituitary–adrenal (HPA) axis…This can cause…type 2 diabetes mellitus…or hypertension. A convincing link between chronic stress and neurodegeneration has been now established in patients with Alzheimer’s disease…Chronic stress can lead to reduced dopaminergic tone [levels]…and higher salivary cortisol levels…Stress reduces regulatory T-lymphocytes by 50% in patients who suffer from post-traumatic stress disorder and a similar profound reduction has been found in PD. Chronic stress has been also found to induce the proinflammatory networks…which in turn activate the HPA axis. Upregulation of cytokines has been linked with sudden death after major emotional trauma… Further, dysregulation of the HPA axis can cause dendritic remodelling, dysfunction of neurogenesis, apoptosis in hippocampal neurons and result in increased oxidative stress…” (emphasis mine)

The prefrontal cortex as a key target of the maladaptive response to stress (2007) “Because prefrontal cortex (PFC) dysfunction characterizes many stress-related disorders, we here analyzed the impact of chronic stress in rats on the integrity of the hippocampal-PFC pathway, monitored by behavioral and electrophysiological function and morphological assessment. We show that chronic stress impairs synaptic plasticity…in addition, it induces selective atrophy within the PFC and severely disrupts working memory and behavioral flexibility, two functions that depend on PFC integrity…” (emphasis mine)

Stress signalling pathways that impair prefrontal cortex structure and function (2009) “The prefrontal cortex (PFC) – the most evolved brain region – subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness…” (emphasis mine)

Chronic stress impairs prefrontal cortex-dependent response inhibition and spatial working memory (2012) “Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition… These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been directly compared within the same animals after chronic stress...” (emphasis mine)

Stress and Sleep Disorder (2012) “…This paper investigates the literature regarding the activity of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems during sleep in order to identify relations between stress and sleep disorder and the treatment of stress-induced insomnia. Sleep and wakefulness are regulated by the aminergic, cholinergic brainstem and hypothalamic systems. Activation of the HPA and/or the sympathetic nervous systems results in wakefulness and these hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol or corticosterone, noradrenaline, and adrenaline, are associated with attention and arousal. Stress-related insomnia leads to a vicious circle by activating the HPA system. An awareness of the close interaction between sleep and stress systems is emerging and the hypothalamus is now recognized as a key center for sleep regulation…” (emphasis mine)

  • The beneficial effects of leptin on REM sleep deprivation-induced cognitive deficits in mice (2013) “Leptin, a 167 amino acid peptide, is synthesized predominantly in the adipose tissues…Recent studies indicate that leptin receptor is expressed with high levels in many brain regions that may regulate synaptic plasticity. Here we show that deprivation of rapid eye movement (REMD) sleep resulted in impairment of both cue and contextual fear memory…Leptin receptors…are expressed with high levels in many extra-hypothalamic brain regions, including the hippocampus, brain stem, cortex, amygdala, and cerebellum implying that leptin may modulate other brain functions as well as regulate energy homeostasis. Indeed…the performance of memory tasks was improved following administration of leptin into the hippocampus. Exposure of hippocampal neurons to leptin resulted in a rapid increase in the density and motility of dendritic filopodia as well as the number of excitatory synapses…In the present study, we have demonstrated that leptin rescues REMD-induced impairment of fear memory consolidation. We further investigated the mechanisms underlying the action of leptin…” (emphasis mine)
  • Quantity and Quality of Sleep and Incidence of Type 2 Diabetes: A systematic review and meta-analysis (2009) Quantity and quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes… Lack of sleep exerts deleterious effects on a variety of systems with detectable changes in metabolic, endocrine, and immune pathways…studies indicate that disturbed or reduced sleep is associated with glucose intolerance, insulin resistance, reduced acute insulin response to glucose, and a reduction in the disposition index, thus predisposing individuals to type 2 diabetes. Causative mechanisms relating sleep problems to adverse health outcomes include reciprocal changes in circulating levels of leptin and ghrelin…Increased cortisol secretion and altered growth hormone metabolism have also been implicated). Low-grade inflammation is activated during short sleep, with possible implications not only for cardiovascular disease but also for other chronic conditions including cancer…” (emphasis mine)

Neuroendocrine Regulation and Metabolism of Glucose and Lipids in Primary Chronic Insomnia: A Prospective Case-Control Study (2013) “The present study investigated whether primary chronic insomnia in otherwise healthy, normal weight women is associated with metabolic and neuroendocrine changes that promote the onset of diabetes. Midnight salivary cortisol concentrations were significantly increased in patients with primary chronic insomnia when compared to controls, indicating dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis…[Study results suggest] dysregulation of HPA is a common feature of both acute and chronic sleep curtailment…Noteworthy, insomnia can also provoke a stress reaction, including the activation of the HPA-axis...Abnormal cortisol levels may precipitate more severe stages of insomnia…” (emphasis mine)

Stress of dying is not suppressed by high-dose morphine or by dementia (2004) “Hypothalamo-pituitary-adrenal (HPA)-axis activation is a response of the organism to psychological and physical stress, resulting in elevated levels of glucocorticoids, mainly cortisol in humans. In our previous studies we found post-mortem blood and cerebrospinal fluid (CSF) cortisol levels to be up to 20-fold higher than in vivo levels. Since clinical observations point to similar strong elevations of cortisol in fatally ill patients, we suggested that the high post-mortem cortisol levels might be due to the stress during the process of dying. We hypothesized that if the cortisol rise during dying is due to the psychological stress of the impending death, then the rise in cortisol should be inversely proportional to the degree of dementia, and that high-dose morphine giving analgesia, sedation, and sleep would suppress this response…High-dose morphine did not cause a suppression of cortisol rise, neither in controls nor in Alzheimer patients. Our results indicate that the extreme elevations of cortisol levels during dying are rather due to the organic stress of the organism than to psychological stress of the patient, and is not suppressed by high-dose morphine.” (emphasis mine)

The role of the hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of alcohol misuse and suicidal behavior in adolescents (2007) “Alterations in the mechanisms that regulate hypothalamic-pituitary-adrenal (HPA) axis activity predate the development of alcohol use disorders. Human and animal studies indicate that chronic alcohol consumption induces a persistent impairment in the ability of the HPA axis to respond to stress. Therefore, HPA axis abnormalities may contribute to the development of alcohol use disorders and may be a result of alcohol misuse. HPA axis interacts with serotonergic mechanisms….An abnormal interaction between the HPA mechanisms and serotonergic systems may substantially contribute to suicidal behavior in adolescents, because abnormalities in HPA and serotonin functions may be inherited and may manifest at young age….HPA dysregulation may contribute to both alcohol abuse and suicidal behavior …” (emphasis mine)

Circadian cortisol, depressive symptoms and neurological impairment in early multiple sclerosis (2011) “There is evidence for the existence of a hyperactive hypothalamus-pituitary-adrenal (HPA) axis and its potential role in disease progression in multiple sclerosis (MS). Depressive symptoms are also common in MS. At the same time, depressive symptoms are often associated with an elevated circadian cortisol secretion. So far, little is known about the interplay between depressive symptoms and circadian HPA axis abnormalities in MS. Here we investigated depressive symptoms, circadian HPA axis function, cortisol awakening response (CAR) and neurological impairment in 32 early stage relapsing-remitting MS (RRMS) patients…RRMS patients expressed a significantly higher CAR when compared to healthy controls….In summary, there is evidence that a hyperactive HPA axis is primarily present in MS patients expressing moderately elevated depressive symptoms. MS patients with only few depressive symptoms do not significantly differ in CAR when compared to healthy controls. To the best of our knowledge, this is the first study showing that in early stage MS, a hyperactive HPA axis is primarily present in patients who express moderate depressive symptoms…” (emphasis mine)

Cortisol awakening response is linked to disease course and progression in multiple sclerosis (2013). “Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has frequently been reported in multiple sclerosis (MS). So far, HPA axis function in MS has predominantly been studied under pharmacological stimulation… Circadian cortisol release, in particular CAR, shows a course specific pattern with most pronounced release in RRMS. There is also some evidence for greater CAR in RRMS patients with EDSS progression. As a consequence, CAR might be of predictive value in terms of neurological disability in RRMS patients. The possible role of neuroendocrine-immune interactions in MS pathogenesis is further discussed….” (emphasis mine)

Metabolic, autonomic and immune markers for cardiovascular disease in posttraumatic stress disorder (2014) “Posttraumatic stress disorder (PTSD) has been associated with significantly greater incidence of heart disease. Numerous studies have indicated that health problems for individuals with PTSD occur earlier in life than in the general population. Multiple mechanistic pathways have been suggested to explain cardiovascular disese (CVD) risk in PTSD, including neurochemical, behavioral, and immunological changes. The present paper is a review of recent research that examines cardiovascular and immune risk profiles of individuals with PTSD. First, we address the relatively new evidence that the constellation of risk factors commonly experienced in PTSD fits the profile of metabolic syndrome. Next we examine the findings concerning hypertension/blood pressure in particular. The literature on sympathetic and parasympathetic responsivity in PTSD is reviewed. Last, we discuss recent findings concerning immune functioning in PTSD that may have a bearing on the high rates of CVD and other illnesses. Our primary goal is to synthesize the existing literature by examining factors that overlap mechanistically to increase the risk of developing CVD in PTSD.” (emphasis mine)

Structural stigma and hypothalamic-pituitary-adrenocortical axis reactivity in lesbian, gay, and bisexual young adults (2014) “Youth exposed to extreme adverse life conditions have blunted cortisol responses to stress.This study aims to examine whether growing up in highly stigmatizing environments similarly shapes stigmatized individuals’ physiological responses to identity-related stress….Lesbian, gay, and bisexual young adults who were raised in highly stigmatizing environments as adolescents evidenced a blunted cortisol response following the TSST compared to those from low-stigma environments. CONCLUSIONS: The stress of growing up in environments that target gays and lesbians for social exclusion may exert biological effects that are similar to traumatic life experiences...” (emphasis mine)

Explicit versus implicit fat-stigma (2012). “Human biologists are increasingly engaging with current global trends toward obesity. However, little is considered about how variation in cultural views of “fat” might shape the biology of obesity, such as through pathways related to socially induced stress. Recent research indicates elevated levels of explicit fat-stigma in middle income nations, suggesting potentially high levels of psychosocial stress around “being fat.” We use the case of Paraguay to test if high levels of explicit prejudice around “being fat” also suggest internalization of those ideas in ways that might predict stress effects…Women in Paraguay reveal high levels of explicit anti-fat bias in an interview on a standard (Attitudes to Obese People) scale, suggesting a shared cultural norm of fat-is-bad. However, Paraguayan women display, on average, no anti-fat stigma in cognitive testing. CONCLUSION: In contrast to what has been observed in industrialized nations, the high levels of explicit fat-stigma does not necessarily correlate with high levels of implicit fat-stigma. This means that pathways between obesity, psychosocial stress, and health outcomes may be very different across socioecological contexts…” (emphasis mine)

Physiological stress response to loss of social influence and threats to masculinity (2014) “Social influence is an important component of contemporary conceptualizations of masculinity in the U.S. Men who fail to achieve masculinity by maintaining social influence in the presence of other men may be at risk of stigmatization. As such, men should be especially likely to exhibit a stress response to loss of social influence in the presence of other men. This study assesses whether men who lose social influence exhibit more of a stress response than men who gain social influence…Cortisol is used as a measure of stress response because it is known to increase in response to loss of social esteem. Results show that young men who lose social influence while working with other young men exhibit cortisol response. In contrast women do not exhibit cortisol response to loss of social influence, nor do men working with women. Results are consistent with the hypothesis that loss of social influence in men may be associated with a physiological stress response…This physiological response to loss of social influence underscores the importance to men of achieving masculinity through gaining and maintaining social influence, and avoiding the stigma associated with the failure to do so…” (emphasis mine)

Decoupling neural networks from reality: dissociative experiences in torture victims are reflected in abnormal brain waves in left frontal cortex (2006) “From a neuroscience perspective, little is known about the long-term effect of torture. Dissociative experiences and posttraumatic stress disorder are often the results of this experience. We examined psychological dissociation within a group of 23 torture victims and report its manifestations within neural networks in the human brain. In particular, we observed that dissociative experiences are associated with slow abnormal brain waves generated in left ventrolateral frontal cortex. Given that focal slow waves often result from depriving neural networks of major input, the present results may indicate decoupling of frontal affective processors from left cortical language areas. This interpretation is consistent with the fact that disturbed access to structured verbal memory concerning traumatic events is a core feature of the dissociative experience.” (emphasis mine)

The role of abusive states of being in interrogation (2013). Interrogation, the questioning of persons detained by police, military, or intelligence organizations, is designed to extract information that a subject may resist disclosing. Interrogation techniques are frequently predicated on inducing mental states of despair, dread, dependency, and debility that weaken an individual’s resistance. Descriptions of techniques from 2 Central Intelligence Agency training manuals are illustrated by examples from interviews of and writings by Murat Kurnaz, who was held at Guantánamo Bay Detention Camp for 5 years. Interrogation techniques are designed to create a destabilizing sense of shock; undermine an individual’s grasp on reality; and provoke internal psychological division, self-conflict, and confusion. The long-term effects of interrogation often include posttraumatic stress disorder as well as states of anxiety, depression, and depersonalization.” (emphasis mine)

Stimulus deprivation and overstimulation as dissociogenic agents in postmodern oppressive societies (2013) “Societal conditions associated with overstimulation or understimulation may precipitate and maintain oppression among individuals and communities by inducing dissociation. Distortion of reality and the flooding of everyday awareness with irrelevant information by mass media is a type of community-wide overstimulation. Alternatively, stimulus deprivation enables single-minded thinking to be narrowly preoccupied with rigid religious ideas, traditional rituals, and postmodern thought and behavior patterns. Provoked sex is utilized as a soothing tool for those who live in overstimulation and as an opportunity for transient enjoyment and rejuvenation for those who live in stimulus deprivation. Chronic exposure to disproportionate stimuli resurrects the trauma-based developmental detachment between the sociological and psychological selves of the individual at the cost of the latter. The enlarged sociological self of the individual is misused to induce a conforming identity transformation of individuals and entire communities that is a prerequisite to setting and maintaining an oppressive system. Constituting overstimulation itself, the enduring fear of chaos in a world akin to crisis enables deliberate acceptance of oppression to restore a sense of control. In fact, the expectancy of crisis triggers the trauma-related dissociative fears of individual internal chaos, which are misused, in turn, to aggravate fears of external chaos again. By facilitating the denial of internal fears rather than integrating them, psychological theories and practices of the past century have failed in addressing the problem of individual and societal oppression…” (emphasis mine)

This appears to be an appropriate place for me to pause, and contemplate. Or perhaps to invite a new partner to this fiesta, say, some form of entertaining, critical-social-analysis to accompany me on the open road—to see where a balls to the wall rigorous test drive will take us… Coming up (sooner or later):

  • Porges’ Polyvagal Stress Response Theory
  • Scientism as force of domination, tool of oppression and hidden weapon of traumatic stress…

Later! :-)

i like a good mystery

i like a good mystery: Originally Posted on February 23, 2011 by hopefulandfree (i.e. very first personal blog post ever written by “hopefulandfree” in “hopefulandfree’s own blog.) :-)

Every good blogger is supposed to have a focus. A main idea. That’s how you build an audience. The reader feels a need to sense where all this is leading.

See? You’re curious, right? A little bit curious…?

And yet. Already this outcome-oriented notion does not set well with me. Feels like crazy making. I want to explore–rather than know things in advance.

So. This blog isn’t about making things happen. It’s not about predicting or controlling the outcome of anything.

It’s about something else. What? I’m not sure.

I guess we’ll find out together.

Or maybe not.

sister heart

sister heart: Originally posted on May 1, 2011 by hopefulandfree

My sister finished her marathon,

sat in green glass, dog hair, razor wire, TV remote,

pushed through in glory to the end,

skull of rat, rusting cola can, black plastic spoon,

smoldering ash, Hello Kitty rain coat,

toilet tank, toothless comb, bicycle spoke,

blood bath. She curled her arms beneath her head,

a pillow of bone. Baby lifeless, limp at breast, her milk let down.

We’ve never met.

Her tears are not my tears. I snip tulips and blue hyacinth.

Her flesh is chocolate brown.

In my kitchen, I eat raisins.

Her eyes are blank.  Mine fill with fear.

No time to second guess. Where is my sister now?

She waits all night for quiet rest.

When it will come.

Please hurry death.

Be done.

Mother fucker.

Be done.


Val on May 4, 2011 at 2:10 pm said:




 Reply ↓


on May 4, 2011 at 3:54 pm said:

Thank you. It was painful to bring out from inside. Worth it, though, after.

lucky me

lucky me: Originally Posted on April 30, 2011 by hopefulandfree

This has been a challenging year.

Husband was seriously injured; he had only recently found employment before that happened, so our savings were about gone. My own surgery had to be postponed so I could help him during his recovery. He lost his job (because of injuries from the wreck he did not cause), which then resulted in our loss of medical insurance. No money, no medical care here in the good old USA. A reality of life that will bite baby boomers hard in the next few years. Will probably bite their adult children too…whether they will be able to help out Mom and Dad, or not.

We came close to losing our home, too–our claim settlement with the auto insurance company looks to be another couple of years away. Or longer. This is simply another reality about which we can do little to influence the outcome. We may lose our home yet because of medical bills. Shrug. Don’t like the thought. Not at all.

My first surgery for disabled hand (number 1)  took place in February. I cannot work until both hands are fixed and my rehab is complete–so another 4 to 5 months. At least. There is no such thing as disability payments for someone like me, who CAN work eventually, but must wait for the necessary medical care, which first must be paid for…yeah. Catch 22 is alive and well.

It is hard to watch my orchard and gardens go without the care they need. No money to hire anyone. Neither my husband nor I are recovered or well enough to do the hard physical labor required. I’m hoping to have a good crop of fruit anyway. I won’t think beyond this year. Does no good.

Always had near perfect credit rating until this year too. A recent attempt to secure a loan had me seeing red. The interest rates they wanted were high double digits, and I still have my creepy student loans to try not to think about…I have become adept at juggling bills (payments) from week to week. Never thought I could learn this skill so well. I’ve gotten even better at ignoring the unpleasant realities about which I can do nothing to change. Good old Serenity Prayer-style thinking…even an athiest can master it, apparently. :)

I am highly over-educated and have no recent experience that employers concern themselves with when they decide who to hire. Jobs in this area are scarce, too. I will have to apply as a new-grad RN when in fact I graduated over a year ago, but circumstances have prevented me from seeking employment, obviously. It’s going to get interesting.

It’s funny, almost. I have a wobbly grasp of theories of quantum physics, some neurobiology and anthropology, a good deal of communication, sociology, philosophy and nursing. My background in literature and rhetoric have allowed me to teach college in the past.

This kind of knowledge is worthless in the marketplace.

Actually, it is funny when I think about it long enough. My dream job: companion to a wealthy older person who needs lots of intellectual stimulation and a bit of nursing care. LOL. I have a loving heart. That counts for something, right?

Most people don’t realize that college instructors (non tenured or adjunct faculty) earn less than minimum wage when you consider the prep time and grading/analysis of essays (the kind of teaching I did). Teaching college was just about my favorite job ever, after being a mom, of course, but I almost went broke doing it. No economic-related benefits there at all. Great opportunity to learn to love people of all kinds.

At times like this I think about the billions (yes, billions, not millions) of people who earn less than $5 a day, have no secure home, and no idea where they will find food for the next day. Many of these people are children. Many or most have lived under oppressive conditions for their entire lives. They live with hunger every day. (Or most of the time.) Even when they can manage to get sufficient calories they are deficient in protein, and therefore their brain functions–among other physiological systems–deteriorate. The chronic stress of poverty and oppression are double-edged killers.

People living with chronic poverty and hunger often blame themselves for being weak, for struggling in vain to find work that pays enough to survive. They think that God is punishing them, or they believe they could have somehow done more, lived better lives to lessen their struggle.

Or they just put one foot in front of the other for as long as they can. Then they lay down and die. From disease, from malnutrition, from starvation, from sheer exhaustion and from physical disorders caused by long-term trauma. Trauma, that’s what poverty and oppression really are. Each day is another trauma connected to the day before and to the day yet arrived. If human beings such as these are lucky, there is some form of community around them, but even then–in the end– it is every person for himself or herself.

I’ve seen children just barely surviving on the streets, without guardians except for other children, and it is impossible to imagine the mindset or the kind of thinking required. I used to give them money. Some have no limbs, lost to an unimaginable event or unending disease process. They use make-shift crutches and skateboard-like devices to push themselves around. Cobblestones and dirt hills are a son of bitch to maneuver.

This week I had a weird attack of  fibromyalgia, the first bad one in a long time. Every muscle in my back and arms felt tight and painful. Extremely painful. It was a gentle little reminder of the chronic pain that I once lived with almost daily. Bah. I took a few pills, rested, ate carefully, and went on with my life the next day.

Strange experience, that.

It told me, very loudly and clearly: I am so fucking fortunate.

Today. And today is all any of us have.

Anyway. That’s me. Now. A bit whiny. Very grateful.