Exposed to events that never happen: generalized unsafety, the default stress response, and prolonged autonomic activity
Open accessAbstract
Based on neurobiological and evolutionary arguments, the generalized unsafety theory of stress (GUTS) hypothesizes that the stress response is a default response, and that chronic stress responses are caused by generalized unsafety (GU), independent of stressors or their cognitive representation. Three highly prevalent conditions are particularly vulnerable to becoming 'compromised' in terms of GU, and carry considerable health risks: Thus, GUTS critically revises and expands stress theory, by focusing on safety instead of threat, and by including risk factors that have hitherto not been attributed to stress.
AI snapshot
Written from the paper’s full text.
TL;DR
This theoretical paper proposes the Generalized Unsafety Theory of Stress (GUTS), arguing that the stress response is a default state that is normally tonically inhibited and only disinhibited when safety is not perceived. Chronic stress responses are therefore attributed to generalized unsafety (GU) rather than to stressors or their cognitive representation.
Key findings
As a conceptual paper, GUTS advances hypotheses rather than reporting new empirical results:
- The stress response is framed as a default response, "not triggered, but disinhibited," normally under tonic inhibition by the prefrontal cortex (vmPFC) and reflected in high resting heart rate variability (HRV); withdrawal of that inhibition is reflected in low HRV.
- Three "safety-compromised" domains are proposed as sources of GU: compromised bodies (obesity, low aerobic fitness, older age), compromised social network (loneliness), and compromised contexts (neutral contexts that acquire threat value through context conditioning, e.g. work stress).
- Cited supporting evidence includes a rodent finding that high-frequency HRV correlates 0.88 with vagus nerve activity (Kuo et al., 2005), a suggested clinical cut-point of daytime RMSSD below 30 ± 5 ms marking greater risk (Jarczok et al., 2015), and work stress in the highest quartile increasing cardiovascular disease risk up to 3.6 times (Bosma et al., 1998).
- Low HRV is reported to predict stress responses to safe/neutral stimuli, including heightened startle to neutral stimuli in men (Ruiz-Padial et al., 2003), diminished safety learning and slow extinction (Pappens et al., 2014; Wendt et al., 2015), and amplified contextual fear conditioning (Melzig et al., 2009).
Methods
This is a theoretical/review article, not an empirical study; no new data or sample are reported. The argument is built from neurobiological evidence (prefrontal inhibition of subcortical sympathoexcitatory circuits, amygdala–mPFC connectivity, HRV as a vagal index) and evolutionary reasoning (erring on the side of caution; the "smoke detector principle"). It synthesizes prior literature on predictability/unpredictability, safety learning during development, and the three compromised domains to derive testable predictions.
Limitations
The paper states that the expectation of high GU levels in compromised-body conditions "largely remains to be tested," and identifies the key testable implication of GUTS as shifting focus from threat signals to identifying key signals of safety. Evident from the text: the theory is presented without new empirical data, and much of the supporting evidence is cited from other studies rather than directly tested here; the schematic figures (Fig. 1, Fig. 2) are explicitly described as hypothetical illustrations in which "the physiological response magnitude will vary across time as a function of the extent of perceived unsafety."
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Integrity signals
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Cites
Statistics
Claims the paper makes
0 of 58 cited sources checked · 0 supported · 0 flagged
- Interpretationreasoning
Not being able to switch off or inhibit the default stress response is not dependent on actual stressors or PC; perceived GU is sufficient.
“A key principle of GUTS is that not being able to switch off, or inhibit the default stress response is not dependent on actual stressors or PC: perceived GU is sufficient, GU is the crucial element here.”
Quote in the paperNot a substantial claim - Interpretationreasoning
In conditions with reduced bodily capacity, namely obesity, low aerobic fitness and older age, GU is preserved due to its evolutionary survival value.
“in conditions with reduced bodily capacity, namely obesity, low aerobic fitness and older age, GU is preserved due to its evolutionary survival value”
Quote in the paperNot a substantial claim - Interpretationreasoning
In case of specific stressors, daily contexts that are neutral by themselves may become unsafe by previously being paired with stressors, via context conditioning.
“in case of specific stressors (e.g.work stressors), daily contexts that are neutral by themselves (e.g. office building, email at home) may become unsafe by previously being paired with stressors, via context conditioning.”
Quote in the paperNot a substantial claim - Interpretationreasoning
GU causes the default stress response to remain activated whenever the organism fails to perceive safety in situations that are not intrinsically dangerous.
“GU causes the default stress response to remain activated, whenever our phylogenetically ancient mind-body organism fails to perceive safety in a wide range of situations in modern society that are not intrinsically dangerous.”
Quote in the paperNot a substantial claim - Premisecitation
PC may be largely unconscious but still leads to prolonged physiological stress responses.
“PC may even be largely unconscious (Brosschot, 2010;Brosschot et al., 2010) but still leads to prolonged physiological stress responses (ibidem).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Brosschot, 2010
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- cites Brosschot et al., 2010
Not checked in the free run.
- Interpretationreasoning
GUTS predicts prolonged and even chronic stress responses occur when no actual stressors or cognitive representations of stressors are present, because of continuous failure to perceive safety.
“it predicts how prolonged and even chronic stress responses occur when no actual stressors (threats) are present at all, or even cognitive representations of stressors, because of the continuous failure to perceive safety.”
Quote in the paperNot a substantial claim - Premisereasoning
Despite growing evidence that PC causes prolonged physiological responses, it is still far from explaining most protracted stress responses associated with chronic stressors.
“Despite growing evidence that PC causes prolonged physiological responses, especially for cardiovascular and endocrine (i.e.cortisol) activity (Brosschot et al., 2006;Ottaviani et al., 2015;Verkuil et al., 2010;Zoccola and Dickerson, 2012), it is still far from explaining most of, let alone all of, the often extremely protracted stress responses associated with chronic stressors such as work stres”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Brosschot et al., 2006 source
Not checked in the free run.
- cites Ottaviani et al., 2015
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- cites Verkuil et al., 2010 source
Not checked in the free run.
- Rests on an assumption: The underlying psychophysiological mechanisms of the stress-disease link remain poorly specified.
- Premisecitation
Psychosocial stress, including chronic anxiety, is a major risk factor for somatic disease, including cardiovascular disease.
“Psychosocial stress, including chronic anxiety, is a major risk factor for somatic disease, including cardiovascular disease”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
The stress response is a default response of the organism, automatically fallen back upon when no other information is available.
“the stress response is a default response”
- Also stated in: § 2. The generalized unsafety theory of stress (GUTS) · plain
“the stress response is a default response of the organism, and that it is the response the organism automatically falls back upon when no other information is available.”
- Also stated in: § 3. Feeling unsafe in a safe world: the neurobiological and evolution-theoretical basis of GUTS · plain
“the stress response is default, it is 'always there', on the verge of being activated, only being inhibited when safety is clearly perceived.”
Quote in the paperSubstantial claim0 of 3 sources checked - Also stated in: § 2. The generalized unsafety theory of stress (GUTS) · plain
- Interpretationreasoning
Chronic stress responses are caused by generalized unsafety (GU), independent of stressors or their cognitive representation.
“chronic stress responses are caused by generalized unsafety (GU), independent of stressors or their cognitive representation.”
- Also stated in: § 2. The generalized unsafety theory of stress (GUTS) · hedged
“We hypothesize that the mechanism that explains most chronic stress responses in daily life is the generalized perception of unsafety (GU)”
- Also stated in: § 6. Three 'safety-compromised' domains with chronic stress responses · plain
“the major hypothesis of GUTS is that prolonged physiological stress responses are caused by generalized perceptions of unsafety (GU).”
Quote in the paperSubstantial claim - Also stated in: § 2. The generalized unsafety theory of stress (GUTS) · hedged
- Interpretationreasoning
Due to GU, chronic stress responses occur in an objectively safe world, with no threatening information.
“Due to GU, chronic stress responses occur in an objectively safe world, with no threatening information.”
Quote in the paperNot a substantial claim - Interpretationnone given
The automatic generalized perception of unsafety is the crucial explanatory mechanism for chronic physiological responses.
“we take a radically different viewpoint by posing that not PC but the automatic (i.e.largely unconscious) 'generalized perception of unsafety' is the crucial explanatory mechanism.”
Quote in the paperNot a substantial claim - Premisecitation
Chronic anxiety can be conceptualized as a chronic psychobiological stress response in the absence of realistic stressors.
“the latter can be easily conceptualized as a chronic psychobiological stress response in the absence of realistic stressors”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Some of the biggest and growing health risks in modern society (obesity, aerobic unfitness etc. and loneliness) may be at least partly due to chronic stress responses.
“This basically implies that some of the biggest -and growing -health risks in modern society (obesity, aerobic unfitness etc. and loneliness) may be at least partly due to chronic stress responses!”
Quote in the paperNot a substantial claim - Interpretationreasoning
During activation of the brain's default mode network, the default stress response is typically inhibited.
“Thus, during activation of the brain's 'default mode network', the default stress response is typically inhibited.”
Quote in the paperSubstantial claim - Premisecitation
Even if safety cues are available, they are often not recognized.
“Importantly, more recent studies have shown that even if safety cues are available, they are often not recognized (e.g.Maren et al., 2013;Melzig et al., 2009;Pappens et al., 2014;Ruiz-Padial et al., 2003;Wendt et al., 2015).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
People in these conditions are not recognizing sufficient safety to inhibit the default stress response.
“In terms of GUTS: these people are not recognizing sufficient safety to inhibit the default stress response.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Low resting HRV (vagal withdrawal) is an index of the chronically disinhibited default stress response.
“Therefore, in GUTS terminology, low resting HRV ('vagal withdrawal') is an index of the chronically disinhibited default stress response.”
Quote in the paperSubstantial claim - Interpretationcitation
GU is linked to low HRV, even when stressors are absent.
“Thus: GU is linked to low HRV, even when stressors are absent.”
Quote in the paperSubstantial claim - Interpretationreasoning
The crucial prolonged stress responses did not occur during the unpredictable stressors, but during the periods in between stressors.
“the crucial -because prolonged -stress responses did not occur during the unpredictable stressors, but during the periods in between stressors!”
Quote in the paperNot a substantial claim - Interpretationreasoning
There are three distinct major domains particularly vulnerable to development or maintenance of GU later in life: body, social network, and context.
“In our view there are three distinct major domains that are particularly vulnerable to the development or maintenance of GU later in life: our body, that should be sufficiently capable to deal adequately with the threats of our ancestral habitat; our social network, which should provide the primary safety signal for social animals such as humans; our context, which in modern society is, despite oc”
Quote in the paperSubstantial claim - Interpretationreasoning
The generalization of safety or unsafety is partly a function of our fitness, that is, our physical capability to cope with stressors.
“The generalization of safety (or unsafety) is, partly, a function of our fitness, that is, our physical capability to cope with stressors.”
Quote in the paperSubstantial claim - Interpretationnone given
The direction of learning is not from no fear toward anxiety but from general anxiety toward specific fear.
“Importantly, the direction of learning is not from no fear toward anxiety but from general anxiety toward specific fear.”
Quote in the paperSubstantial claim - Premisecitation
Removal of prefrontal inhibition permits rather than causes an increase in physiological activity (disinhibition).
“The notion that removal of prefrontal inhibition”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Hughlings Jackson, 1884
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- cites Thayer et al., 2012 source
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- Interpretationreasoning
The stress response is not triggered, but disinhibited.
“Thus, the stress response is not triggered, but disinhibited.”
Quote in the paperSubstantial claim - Premisecitation
Not recognizing safety is not restricted to people suffering from stressors or anxiety.
“Moreover, not recognizing safety is not restricted to people suffering from stressors or anxiety (Pappens et al., 2014;Ruiz-Padial et al., 2003;Wendt et al., 2015).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
During a stressor that turns out to be safe (controllable), amygdala activity is again inhibited by the PFC.
“Conversely, during a stressor that turns out to be safe (controllable) amygdala activity is again inhibited by the PFC (Motzkin et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Motzkin et al., 2015 source
Not checked in the free run.
- Interpretationreasoning
If an organism never experiences a stressor it will never learn the capacity to control stressors, and thus safety.
“If an organism never experiences a stressor it will never learn the capacity to control stressors, and thus safety.”
Quote in the paperNot a substantial claim - Premisecitation
A large range of conditions not directly related to stress, such as obesity, low aerobic fitness and old age, are associated with chronic low HRV.
“A large range of conditions that are, at first glance, not directly related to stress, such as obesity, low aerobic fitness and old age (Thayer et al., 2010;Zulfiqar et al., 2010) and many other 'low capacity' bodily states (Thayer et al., 2010), are still associated with chronic low HRV.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Various forms of bodily unfitness cause an overestimation of physical challenges: for example they make a distance to a target seem greater and a hill seem steeper.
“A possibly less evident example is that it has been consistently found that various forms of bodily unfitness cause a overestimation of physical challenges: for example they make a distance to a target seem greater and a hill seem steeper (Proffitt, 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Proffitt, 2006 source
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- Premisecitation
For social animals such as humans, social safety signals are the most important.
“For social animals such as humans, the social safety signals are the most important (cf.Coan's Social Baseline Theory;Coan, 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Coan, 2010 source
Not checked in the free run.
- Interpretationcitation
In all conditions that compromise bodily fitness, the stress response is more on edge, as reflected in a low HRV.
“Therefore, in all these conditions the stress response is more 'on edge', as reflected in a low HRV (Thayer et al., 2010;Zulfiqar et al., 2010).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
A second domain in which perceptions of unsafety may become generalized is the personal social network or the lack thereof.
“A second domain in which perceptions of unsafety may become generalized, is that of the personal social network -or the lack thereof.”
Quote in the paperSubstantial claim - Interpretationcitation
The third personal domain in which GU and low HRV may occur is in situations or environments that are neutral (safe) by themselves, but that have acquired a threat value by their association with a stressor, through context conditioning.
“So, the third personal domain in which GU and low HRV may occur is in situations, or environments that are neutral (safe) by themselves, but that have acquired a threat value by their association with a stressor, through context conditioning (Grillon et al., 2006;Melzig et al., 2009).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
This protracted disinhibition occurs even when we do not have any (un)conscious stress-related thoughts (PC), either triggered or not by these contexts.
“Crucially, this is also the case when we do not have any (un)conscious stress-related thoughts (PC), either triggered or not by these contexts.”
Quote in the paperNot a substantial claim - Interpretationcitation
A compromised body does not provide sufficient bodily information to allow the brain to predict complete safety.
“In neurobiological terms, a compromised body does not provide sufficient bodily information to allow the brain to predict complete safety (Smith et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Smith et al., 2015 source
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- Premisecitation
There is a dose response relationship between lower social integration and physiological dysregulation.
“A recent study even found a dose response relationship between lower social integration and physiological dysregulation (Yang et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yang et al., 2016
Not checked in the free run.
- Interpretationreasoning
Neither stressors nor their cognitive representation (PC), whether conscious or unconscious, are necessary for a chronic default stress response to remain activated (i.e. not inhibited).
“Again, the point here is that neither stressors nor their cognitive representation (PC), whether conscious or unconscious, are necessary for a chronic default stress response to remain activated (i.e.not inhibited).”
Quote in the paperNot a substantial claim - Interpretationcitation
The generalization of safety (or unsafety) is not only a function of the capacity of the body and the availability of primary safety (social network), but also of learning experiences.
“The generalization of safety (or unsafety) is not only a function of the capacity of the body and the availability of primary safety (social network), but also of learning experiences.”
Quote in the paperSubstantial claim - Interpretationreasoning
The default stress response can continue until the stressor-free but stressor-related context is abandoned, whether that context is real or merely cognitively represented.
“The latter can in fact continue until the stressor-free but stressor-related context is abandoned, whether that context is real or merely cognitive represented.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Despite increased objective environmental safety, modern human bodies still respond in a similar manner.
“Importantly, despite the increased objective environmental safety, modern human bodies still respond in a similar manner.”
Quote in the paperSubstantial claim - Premisecitation
Belonging to a cohesive and supporting social network or perceiving sufficient friendly people around is linked to an increased HRV.
“and is linked to an increased HRV (Porges, 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Porges, 2007 source
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- Premisecitation
In social anxiety, chronic low HRV has been reported.
“Interestingly, in another common condition in which the social network is compromised, that is social anxiety, chronic low HRV has been reported (e.g.Licht et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Licht et al., 2009 source
Not checked in the free run.
- Interpretationreasoning
The stress response initially linked to the real situation of being bullied might get linked to contexts related to work and even to non-stressor-related but work-related thoughts.
“the stress response, that is initially linked to the real situation of being bullied, might get linked to contexts related to work (office, building, area, email at home, etc.) and even to non-stressor-related but work-related thoughts.”
Quote in the paperSubstantial claim - Interpretationreasoning
Stress-related cognition is no requirement for a continued default stress response.
“In other words: stress-related cognition is no requirement for a continued default stress response.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The most important ill health causing aspect of loneliness seems to be the continuous lack of something important, namely social contact.
“The most important ill health causing aspect seems to be the continuous lack of something important, namely social contact.”
Quote in the paperNot a substantial claim - Interpretationreasoning
There are virtually endless realistic combinations of stressors leading to GU to their contexts and subsequent seriously protracted stress responses.
“There are virtually endless realistic combinations of stressors leading to GU to their contexts and subsequent seriously protracted stress responses.”
Quote in the paperNot a substantial claim - Interpretationreasoning
GUTS proposes that this explains a considerable part of the autonomic imbalance and high disease risk that accompanies conditions with compromised bodies.
“GUTS proposes that this explains a considerable part of the autonomic imbalance and high disease risk that accompanies these conditions.”
Quote in the paperSubstantial claim - Premisecitation
People suffering from the stressor of financial debt carry an increased risk for disease.
“For example, people suffering from the stressor of financial debt carry an increased risk for disease (Rosengren et al., 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rosengren et al., 2004 source
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- Premisecitation
Loneliness predicts increased morbidity and mortality even after adjusting for health behaviours.
“Loneliness predicts increased morbidity and mortality even after adjusting for health behaviours (ibidem).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cacioppo et al., 2015 source
Not checked in the free run.
- Interpretationreasoning
In compromised contexts (chronic stress), daily contexts that are neutral by themselves may become unsafe via context conditioning.
“(3) 'Compromised contexts', e.g.chronic stress, in which daily contexts that are neutral by themselves may become unsafe via context conditioning.”
Quote in the paperNot a substantial claim - Premisecitation
Caregiving for a spouse with Alzheimer is associated with enhanced cardiovascular risk.
“Or the situation of caregiving for a spouse with Alzheimer, which is associated with enhanced cardiovascular risk (Lee et al., 2003)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lee et al., 2003 source
Not checked in the free run.
- Interpretationreasoning
Chronic stress responses are due to generalized unsafety (GU).
“Chronic stress responses are due to generalized unsafety (GU).”
Quote in the paperSubstantial claim - Interpretationreasoning
If safety is not detected, regardless of presence of any stressor or its cognitive representation, PFC inhibition is withdrawn, and the default stress response is unleashed, reflected in a low HRV.
“If not, regardless of presence of any stressor or its cognitive representation, PFC inhibition is withdrawn, and the default stress response is unleashed, reflected in a low HRV.”
Quote in the paperNot a substantial claim - Interpretationreasoning
GU in originally safe contexts greatly expands the likelihood for prolonged stress responses and related health risk.
“Obviously, this greatly expands the likelihood for prolonged stress responses and related health risk.”
Quote in the paperNot a substantial claim - Interpretationnone given
The stress response is a default response that is normally under tonic inhibition.
“The two core ideas are that: (1) the stress response is a default response that is normally under tonic inhibition;”
Quote in the paperNot a substantial claim - Interpretationreasoning
People with financial debt may frequently fail to shut down their default stress response not so much because of actual exposures to their stressor or thoughts thereof, but far more by being faced almost continuously with a myriad of contexts associated with the stressor that have become 'unsafe'.
“They may very frequently fail to shut down their default stress response not so much because of the number of actual exposures to their stressor or thoughts thereof, but far more by being faced almost continuously with a myriad of contexts that are associated with the stressor, that have become 'unsafe': e.g.shops, financial newspaper pages, signs of Euro's (or other currencies), wallets, banks.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Chronic stress is not due to the presence of something (i.e. stressors, threat) but the lack of something else: safety.
“Chronic stress is not due to the presence of something (i.e.stressors, threat) but the lack of something else: safety.”
Quote in the paperSubstantial claim - Interpretationreasoning
In compromised bodies (obesity, low aerobic fitness, older age), GU is preserved due to its evolutionary survival value, i.e. to lower the threshold for the stress response because of a reduced bodily capacity to deal successfully with stressors.
“We identified three domains of life in which GU can develop and which we call 'compromised': (1) 'Compromised bodies': e.g.obesity, low aerobic fitness and older age, in which GU is preserved due to its evolutionary survival value, i.e. to lower the threshold for the stress response because of a reduced bodily capacity to deal successfully with stressors (fight or flight);”
Quote in the paperNot a substantial claim - Interpretationreasoning
Only when safety is detected, there is PFC inhibition of subcortical areas, especially the amygdala, which is reflected by a high resting HRV.
“Only when safety is detected, there is PFC inhibition of subcortical areas, especially the amygdala, which is refelected by a high resting HRV.”
Quote in the paperNot a substantial claim - Interpretationreasoning
When no safety is perceived, the default response remains uninhibited.
“(2) when no safety is perceived, the default response remains uninhibited.”
Quote in the paperSubstantial claim
- May combine two claims. 27
- Classified as probably not a substantial claim. 13
May combine two claims.
PremisecitationWhen safety is in doubt, subcortical inhibition by the vmPFC is decreased and amygdala activity is enhanced.
“When safety is in doubt, subcortical inhibition by the vmPFC is decreased and amygdala activity is enhanced (Grupe and Nitschke, 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Grupe and Nitschke, 2013 source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable), S4 (based).
InterpretationreasoningGUTS has far greater explanatory ability than other current stress theories.
“The GUTS has a far greater explanatory ability than other current stress theories.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationPC is a core element in chronic stress and chronic anxiety.
“PC is not only a core element chronic stress, but also in chronic anxiety”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenIt seems unlikely that people think incessantly about their stressors, either consciously or unconsciously.
“It seems unlikely that people think incessantly about their stressors, either consciously or unconsciously”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationThe stress response is mediated by subcortical areas including the amygdala, and is normally under continuous tonic inhibition by the prefrontal cortex (PFC), more specifically the ventromedial PFC (vmPFC).
“The stress response is mediated by subcortical areas in the brain, i.e. the so called limbic structures, including the amygdala, and it is normally under continuous ('tonic') inhibition by the prefrontal cortex (PFC; Ahern et al., 2001), more specifically by the ventromedial PFC (vmPFC; Motzkin et al., 2015).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningWhen stressors cannot clearly be predicted, the safety of the surroundings is not guaranteed, and the stress response remains disinhibited, even in the temporal absence of stressors.
“When stressors cannot clearly be predicted, the safety of the surroundings is not guaranteed, and the stress response remains disinhibited, even in the (temporal) absence of stressors.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningInherited psychological vulnerability, chronic prenatal maternal stress and chronic early life stress determine relatively stable, change-resistant GU.
“Some of these 'failures' seem to determine relatively stable, change-resistant GU, such as inherited psychological vulnerability (e.g.traits such as neuroticism), chronic prenatal maternal stress and chronic early life stress.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThe world was generally less safe for people in conditions that compromise bodily fitness, and it had survival value not to inhibit the default stress response.
“The world was generally less safe for people in these conditions, and it had survival value not to inhibit the default stress response.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningAccording to GUTS it is more likely that chronic early life stress prevents the brain from learning the complexities of safety contingencies, and thus from growing the neural structures subserving this knowledge.
“However, according to GUTS it is more likely that chronic early life stress prevents the brain from learning the complexities of safety contingencies, and thus from growing the neural structures subserving this knowledge.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningWhen compromised, these domains carry highly prevalent major risk factors for somatic disease in modern society: in body, obesity, old age or aerobic unfitness; in social network, loneliness; daily contexts may become unsafe through contextual fear conditioning.
“We chose these three domains not only because their 'safety failures' are potentially changeable, but also because when 'compromised' they carry highly prevalent major risk factors for somatic disease in modern society: in our body, e.g.obesity, old age or aerobic unfitness; in our social network, e.g.loneliness, and our daily contexts may become unsafe through contextual fearconditioning.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningDisinhibition of the default stress response takes little time, but is costly, and when prolonged it may lead to biological dysregulation and disease.
“On the contrary, its disinhibition takes little time, but is costly, and when prolonged it may lead to biological dysregulation and disease.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe presence of safety inhibits stress-induced neural activity, in contrast to the prevalent view that such activity is induced by a lack of control.
“The presence of safety inhibits stress-induced neural activity, in contrast to the prevalent view that such activity is induced by a lack of control (Amat et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Amat et al., 2005 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationBodily information, mediated by afferent visceral neural pathways, sometimes referred to as gut feelings, although largely unconscious, is an inseparable part of the organism's emotional state.
“Bodily information, mediated by afferent visceral neural pathways, sometimes referred to as”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Damasio, 1991
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- cites Mayer, 2011 source
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May combine two claims.
InterpretationcitationAt the start of life, we all start with the default stress response, but soon we learn to predict safety signals, reflected in increasing HRV.
“At the start of our life, when we leave the safe uterine world, we all start with the default stress response, but soon we learn to predict the safety signals around us: the conditions under which hunger and thirst are satisfied, when affiliation needs are being met, reflected in an increasing HRV (Porges, 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Porges, 2007 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe inhibition of the default stress response when safety is perceived may take time to be established, but it is not costly to prolong it.
“Thus, the inhibition of the default stress response when safety is perceived, may take time to be established, but it is not costly to prolong it.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenOrganisms are intolerant for uncertainty by default.
“organisms are intolerant for uncertainty by default.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone givenIn earlier stages of evolution, an obese body meant a serious reduction in fight/flight ability in the face of ubiquitous threats of ancestral life.
“In earlier stages of our evolution, an obese body meant a serious reduction in fight/flight ability in the face of the ubiquitous threats of ancestral life.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningMerely having a low resting heart rate variability seems sufficient for not recognizing safety, and thus GU.
“In fact, merely having a low resting heart rate variability (HRV) seems sufficient for not recognizing safety, and thus GU.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationScoring in the highest quartile of work stress increases cardiovascular disease risk up to 3.6 times in a dose response fashion, with follow-up times of between 4 and 12 years.
“For example, scoring in the highest quartile of work stress increases cardiovascular disease risk up to 3.6 times (Bosma et al., 1998) in a dose response fashion (Chandola et al., 2008), with follow-up times of between 4 and 12 years.”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationJulius (1995) argued that autonomic imbalance as indexed by chronic low HRV in overweight and related conditions such as diabetes was due to chronic 'hypervigilance' or 'defense' responses.
“Julius (1995) argued before that autonomic imbalance as indexed by chronic low HRV in overweight and related conditions such as diabetes was due to chronic 'hypervigilance' or 'defense' responses.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Julius (1995) source
Not checked in the free run.
May combine two claims.
InterpretationreasoningMany stressor-free but stressor-related contexts may become largely unconsciously perceived as unsafe and lead to a protracted disinhibition of the default stress response.
“In this way many stressor-free but stressorrelated contexts, in which we spend a large part of our daily life, may become -largely unconsciously -perceived as unsafe and lead to a protracted disinhibition of the default stress response.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningGU is the cause of the chronic stress responses in loneliness, and not stressors.
“We argue that it is GU that is the cause of the chronic stress responses in loneliness, and not stressors, as illustrated in Fig. 1f and in Fig. 2b ('all contexts').”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationResponses to the working environment can become context-conditioned because of the potential presence of bullying colleagues, or responses to the home environment in the case of marital discord.
“For example, responses to the working environment can become context-conditioned (Maren et al., 2013) because of the potential presence of bullying colleagues, or responses to the home environment in the case of marital discord.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Maren et al., 2013 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningGUTS is the first theory that explains the chronic low HRV shared by older age, obesity, and similar conditions by an overarching principle of generalized unsafety (GU) and the default stress response, and is more scientifically parsimonious.
“Although in each of these very different conditions (i.e.older age, obesity, etc.) there are biological pathways that may partially explain low HRV, GUTS is the first theory that explains the chronic low HRV that they share by an overarching principle -GU and the default stress response -which is much more scientifically parsimonious.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningWith such a lack of information the system falls back upon the default and therefore the default stress response is chronically active, not inhibited, as reflected in low HRV.
“With such a lack of information the system falls back upon the default and therefore the default stress response is chronically active (i.e.not inhibited, as reflected in low HRV)”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationEvidence is growing for chronic autonomic (including low HRV) and endocrine stress responses in lonely animals and humans, which likely mediates their health risk.
“Evidence is growing for chronic autonomic (including low HRV) and endocrine stress responses in lonely animals and humans which likely mediates their health risk (ibidem; Hawkley et al., 2003).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationWorkplace bullying forms a serious health risk.
“For example, in the case of the work stress type of bullying, which forms a serious health risk (Nielsen et al., 2012;Verkuil et al., 2015)”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationBelonging to a cohesive and supporting social network or simply perceiving sufficient friendly people around appears vital.
“Specifically, belonging to a cohesive and supporting social network or simply perceiving sufficient friendly people around appears vital (Cacioppo et al., 2015)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cacioppo et al., 2015 source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningIn terms of GUTS, loneliness is a condition in which the social network is compromised, that is, the primary source of safety is generally unavailable.
“In terms of GUTS, loneliness is a condition in which the social network is compromised, that is, the primary source of safety is generally unavailable.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningStress-related contexts do not only cause prolonged disinhibition of the default response by triggering (un)conscious stress-related thinking, but also, and much more often, by failing to offer a perception of safety.
“Thus, the stress-related contexts do not only cause prolonged disinhibition of the default response by triggering (un)conscious stress-related thinking, but also, and much more often, by failing to offer a perception of safety.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S1 (asserted), S4 (based). May combine two claims.
InterpretationreasoningPeople suffering from any type of work stress show prolonged low HRV in work related contexts without actual stressors or PC, and these low HRV responses are due to GU.
“GUTS's hypothesis is that people suffering from any type of work stress show prolonged low HRV in work related contexts without actual stressors or PC, and that these low HRV responses are due to GU.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationJulius did not generalize his explanation to other 'compromised body' conditions and did not interpret those responses in terms of default stress responses caused by GU.
“However, he did not generalize this to other 'compromised body' conditions, and did not interpret those responses in terms of default stress responses caused by GU.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Julius (1995) source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenIn compromised social network (loneliness), the primary source of safety, i.e. being part of a cohesive social network, is lacking.
“(2) 'Compromised social network', e.g.loneliness, in which the primary source of safety, i.e. being part of a cohesive social network, is lacking;”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
InterpretationreasoningA teenager fearing social exclusion has a disinhibited default stress response during the many hours of handling a smart phone or computer without these devices necessarily triggering any conscious or unconscious PC.
“Another example is the teenager fearing social exclusion who has a disinhibited default stress response during the many hours of handling a smart phone or computer -again without these devices necessary triggering any conscious or unconscious PC.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S4 (based).
Interpretationnone givenMany examples exist of how GU can develop in originally safe contexts.
“Clearly, there are many examples of how GU can develop in originally safe contexts.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningIn healthy, well-adapted organisms, PFC inhibition is the norm, which is consistent with the finding that neural inhibition is non-costly and highly generalized.
“In healthy, well-adapted organisms, PFC inhibition is the norm, which is consistent with the finding that neural inhibition is non-costly and highly generalized.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningPFC disinhibition of the default stress response is costly, and can cause chronic bodily dysregulation and somatic disease.
“In contrast, PFC disinhibition of the default stress response, is costly, and can cause chronic bodily dysregulation and somatic disease.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningSafety signals are not by definition the counterparts of the signals of threat: for living organisms the absence of threat does not equal the presence of safety.
“Crucially, these safety signals are not by definition the counterparts of the signals of threat: for living organisms the absence of threat does not equal the presence of safety.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The underlying psychophysiological mechanisms of the stress-disease link remain poorly specified.
“Still, the underlying psychophysiological mechanisms remain poorly specified.”
The paper relies on this without support.
It is widely agreed that chronic physiological stress responses are the crucial causal factor leading to disease.
“It is widely agreed that chronic physiological stress responses are the crucial causal factor leading to disease”
The paper relies on this without support.
The precise causes of chronic stress responses have not yet been sufficiently revealed.
“the precise causes of these chronic responses have not yet been sufficiently revealed.”
The authors state this as an assumption.
Predictability and controllability have comparable net results in terms of perceived safety and physiological responses.
“despite conceptual, behavioral and neurobiological (Christianson et al., 2008) differences between predictability and controllability, their net results in terms of perceived safety and physiological responses can be assumed to be comparable.”
The paper relies on this without support.
In loneliness, the primary source of safety is lacking, i.e. being part of a cohesive social network.
“in loneliness the primary source of safety is lacking, i.e. being part of a cohesive social network”
The paper relies on this without support.
Increasingly more people in the modern world have weak or virtually non-existent social networks.
“However, increasingly more people in the modern world have weak or virtually non-existent social networks.”
The paper relies on this without support.
Loneliness is rapidly growing in modern society presumably due to a vicious combination of 'graying' and individualization.
“Loneliness (perceived social isolation; Cacioppo et al., 2015) is rapidly growing in modern society presumably due to a vicious combination of 'graying' and individualization.”
The paper relies on this without support.
Each normal life contains multiple stressors that are unavoidable, and all of us, even those with superior coping skills and generalized perceptions of control, have to face the fact that there are always stressors on the horizon.
“As mentioned earlier, each normal life contains multiple stressors that are unavoidable, and all of us, even those with superior coping skills and generalized perceptions of control (e.g.having high optimism or having an internal locus of control), have to face the fact that there are always stressors on the horizon.”
The paper relies on this without support.
The great health risks of compromised bodies and compromised social network have not hitherto been explained in terms of chronic stress.
“The great health risks of two of these (1 and 2) extremely common conditions have not hitherto been explained in terms of chronic stress.”
The paper relies on this without support.
Many people do not succeed in restricting stress responses to episodes in which stressors actually happen, and cognitively perseverate a lot in between stressors, consciously or unconsciously, causing a lot more stress responses than are strictly necessary.
“Obviously, many of us do not succeed in this, and cognitively perseverate a lot in between stressors, consciously or unconsciously, causing a lot more stress responses than are strictly necessary, as illustrated in Fig. 1b.”
Claims other papers make about this one
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Stress anticipation is relevant in the development of stress-related disorders.
“As such, previous research has highlighted the relevance of stress anticipation in the development of stress-related disorders (Brosschot et al., 2006;Brosschot et al., 2017).”
From Cortisol Response to Stress: The Role of Expectancy and Anticipatory Stress Regulation (2020) · cites this paper as Brosschot et al., 2017
Cites
Porges, S. W. (2007) · Biological Psychology · doi:10.1016/j.biopsycho.2006.06.009 · Cited by 3,415 · see citing works
Thayer, J. F., Åhs, F., Fredrikson, M., Sollers, J. J., & Wager, T. D. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.11.009 · Cited by 3,224 · see citing works
Self-citationSocial isolation, loneliness, and all-cause mortality in older men and women
Steptoe, A., Shankar, A., Demakakos, P., & Wardle, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219686110 · Cited by 2,503 · see citing works
Rosengren, A., Hawken, S., Ôunpuu, S., Sliwa, K., Zubaid, M., Almahmeed, W. A., Blackett, K. N., Sitthi-amorn, C., Sato, H., & Yusuf, S. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17019-0 · Cited by 2,414 · see citing works
Thayer, J. F., Yamamoto, S. S., & Brosschot, J. F. (2010) · International Journal of Cardiology · doi:10.1016/j.ijcard.2009.09.543 · Cited by 2,276 · see citing works
Self-citationUncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective
Grupe, D. W., & Nitschke, J. B. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3524 · Cited by 2,007 · see citing works
McEWEN, B. S., & SEEMAN, T. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb08103.x · Cited by 1,824 · see citing works
Gut feelings: the emerging biology of gut-brain communication
Mayer, E. A. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3071 · Cited by 1,726 · see citing works
Brosschot, J. F., Gerin, W., & Thayer, J. F. (2006) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2005.06.074 · Cited by 1,643 · see citing works
Self-citationThe contextual brain: implications for fear conditioning, extinction and psychopathology
Maren, S., Phan, K. L., & Liberzon, I. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3492 · Cited by 1,547 · see citing works
Functional and chemical anatomy of the afferent vagal system
Berthoud, H.-R., & Neuhuber, W. L. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00215-0 · Cited by 1,280 · see citing works
Urry, H. L., van Reekum, C. M., Johnstone, T., Kalin, N. H., Thurow, M. E., Schaefer, H. S., Jackson, C. A., Frye, C. J., Greischar, L. L., Alexander, A. L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3215-05.2006 · Cited by 1,056 · see citing works
The neuroendocrinology of social isolation
Cacioppo, J. T., Cacioppo, S., Capitanio, J. P., & Cole, S. W. (2015) · Annual Review of Psychology · doi:10.1146/annurev-psych-010814-015240 · Cited by 977 · see citing works
Amat, J., Baratta, M. V., Paul, E., Bland, S. T., Watkins, L. R., & Maier, S. F. (2005) · Nature Neuroscience · doi:10.1038/nn1399 · Cited by 931 · see citing works
Social influences on neuroplasticity: stress and interventions to promote well-being
Davidson, R. J., & McEwen, B. S. (2012) · Nature Neuroscience · doi:10.1038/nn.3093 · Cited by 892 · see citing works
Anxiety and Risk of Incident Coronary Heart Disease
Roest, A. M., Martens, E. J., de Jonge, P., & Denollet, J. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.03.034 · Cited by 865 · see citing works
Autonomic characteristics of generalized anxiety disorder and worry
Thayer, J. F., Friedman, B. H., & Borkovec, T. D. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00136-0 · Cited by 857 · see citing works
Self-citationKim, M. J., Loucks, R. A., Palmer, A. L., Brown, A. C., Solomon, K. M., Marchante, A. N., & Whalen, P. J. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.04.025 · Cited by 838 · see citing works
Two alternative job stress models and the risk of coronary heart disease.
Bosma, H., Peter, R., Siegrist, J., & Marmot, M. (1998) · American Journal of Public Health · doi:10.2105/ajph.88.1.68 · Cited by 831 · see citing works
Social relationships and physiological determinants of longevity across the human life span
Yang, Y. C., Boen, C., Gerken, K., Li, T., Schorpp, K., & Harris, K. M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511085112 · Cited by 751 · see citing works
The physiology of marriage: pathways to health.
Robles, T. F., & Kiecolt-Glaser, J. K. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00160-4 · Cited by 748 · see citing works
Embodied Perception and the Economy of Action
Proffitt, D. R. (2006) · Perspectives on Psychological Science · doi:10.1111/j.1745-6916.2006.00008.x · Cited by 696 · cited 1× · see citing works
“A possibly less evident example is that it has been consistently found that various forms of bodily unfitness cause a overestimation of physical challenges: for example they make a distance to a target seem greater and a hill seem steeper (Proffitt, 2006).”
BackgroundPsychoneuroimmunology: psychological influences on immune function and health
Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.70.3.537 · Cited by 686 · see citing works
Work stress and coronary heart disease: what are the mechanisms?
Chandola, T., Britton, A., Brunner, E., Hemingway, H., Malik, M., Kumari, M., Badrick, E., Kivimaki, M., & Marmot, M. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehm584 · Cited by 673 · see citing works
Loneliness in everyday life: Cardiovascular activity, psychosocial context, and health behaviors.
Hawkley, L. C., Burleson, M. H., Berntson, G. G., & Cacioppo, J. T. (2003) · Journal of Personality and Social Psychology · doi:10.1037/0022-3514.85.1.105 · Cited by 608 · see citing works
Caregiving and risk of coronary heart disease in U.S. women
Lee, S., Colditz, G. A., Berkman, L. F., & Kawachi, I. (2003) · American Journal of Preventive Medicine · doi:10.1016/s0749-3797(02)00582-2 · Cited by 596 · see citing works
Krantz, D. S., & McCeney, M. K. (2002) · Annual Review of Psychology · doi:10.1146/annurev.psych.53.100901.135208 · Cited by 509 · see citing works
A Path Model of Chronic Stress, the Metabolic Syndrome, and Coronary Heart Disease
Vitaliano, P. P., Scanlan, J. M., Zhang, J., Savage, M. V., Hirsch, I. B., & Siegler, I. C. (2002) · Psychosomatic Medicine · doi:10.1097/00006842-200205000-00006 · Cited by 481 · see citing works
Physiological concomitants of perseverative cognition: A systematic review and meta-analysis.
Ottaviani, C., Thayer, J. F., Verkuil, B., Lonigro, A., Medea, B., Couyoumdjian, A., & Brosschot, J. F. (2016) · Psychological Bulletin · doi:10.1037/bul0000036 · Cited by 476 · see citing works
Self-citationVentromedial Prefrontal Cortex Is Critical for the Regulation of Amygdala Activity in Humans
Motzkin, J. C., Philippi, C. L., Wolf, R. C., Baskaya, M. K., & Koenigs, M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.014 · Cited by 454 · see citing works
Going to the heart of the matter
Kubzansky, L. D., & Kawachi, I. (2000) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(99)00091-4 · Cited by 442 · see citing works
The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety
Kim, M. J., & Whalen, P. J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2335-09.2009 · Cited by 433 · see citing works
Kim, M. J., Gee, D. G., Loucks, R. A., Davis, F. C., & Whalen, P. J. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq237 · Cited by 388 · see citing works
Natural selection and the regulation of defenses
Nesse, R. M. (2005) · Evolution and Human Behavior · doi:10.1016/j.evolhumbehav.2004.08.002 · Cited by 365 · see citing works
Reduced Medial Prefrontal Cortex Volume in Adults Reporting Childhood Emotional Maltreatment
van Harmelen, A.-L., van Tol, M.-J., van der Wee, N. J. A., Veltman, D. J., Aleman, A., Spinhoven, P., van Buchem, M. A., Zitman, F. G., Penninx, B. W. J. H., & Elzinga, B. M. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.011 · Cited by 362 · see citing works
Inverse amygdala and medial prefrontal cortex responses to surprised faces
Kim, H., Somerville, L. H., Johnstone, T., Alexander, A. L., & Whalen, P. J. (2003) · NeuroReport · doi:10.1097/00001756-200312190-00006 · Cited by 359 · see citing works
Somatic Effects of Predictable and Unpredictable Shock
Weiss, J. M. (1970) · Psychosomatic Medicine · doi:10.1097/00006842-197007000-00008 · Cited by 357 · see citing works
Environmental influence in the brain, human welfare and mental health
Tost, H., Champagne, F. A., & Meyer‐Lindenberg, A. (2015) · Nature Neuroscience · doi:10.1038/nn.4108 · Cited by 349 · see citing works
Workplace bullying and mental health: a meta-analysis on cross-sectional and longitudinal data
Verkuil, B., Atasayi, S., & Molendijk, M. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135225 · Cited by 348 · see citing works
Self-citationInhibition of the Amygdala: Key to Pathological States?
Quirk, G. J., & Gehlert, D. R. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07087.x · Cited by 308 · see citing works
Unpredictable and uncontrollable events: A new perspective on experimental neurosis.
Mineka, S., & Kihlstrom, J. F. (1978) · Journal of Abnormal Psychology · doi:10.1037//0021-843x.87.2.256 · Cited by 301 · see citing works
Grillon, C., Pine, D. S., Lissek, S., Rabin, S., Bonne, O., & Vythilingam, M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.12.028 · Cited by 272 · see citing works
The relative metabolic demand of inhibition and excitation
Waldvogel, D., van Gelderen, P., Muellbacher, W., Ziemann, U., Immisch, I., & Hallett, M. (2000) · Nature · doi:10.1038/35023171 · Cited by 271 · see citing works
Sakaki, M., Yoo, H. J., Nga, L., Lee, T., Thayer, J. F., & Mather, M. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.05.076 · Cited by 271 · see citing works
Self-citationUnpredictable and uncontrollable events: A new perspective on experimental neurosis.
Mineka, S., & Kihlstrom, J. F. (1978) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.87.2.256 · Cited by 271 · see citing works
van Marle, H. J. F., Hermans, E. J., Qin, S., & Fernández, G. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.05.070 · Cited by 251 · see citing works
Relation of High Heart Rate Variability to Healthy Longevity
Zulfiqar, U., Jurivich, D. A., Gao, W., & Singer, D. H. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.12.022 · Cited by 239 · see citing works
Behavioral control, the medial prefrontal cortex, and resilience
Maier, S. F., Amat, J., Baratta, M. V., Paul, E. D., & Watkins, L. R. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.4/smaier · Cited by 231 · see citing works
Tully, P. J., Cosh, S. M., & Baune, B. T. (2013) · Psychology, Health & Medicine · doi:10.1080/13548506.2012.749355 · Cited by 230 · see citing works
Matthews, K. A., & Gump, B. B. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.3.309 · Cited by 228 · see citing works
Brosschot, J., Verkuil, B., & Thayer, J. (2016) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2016.04.012 · Cited by 226 · see citing works
Self-citationHoehn-Saric, R., McLeod, D. R., Funderburk, F., & Kowalski, P. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.9.913 · Cited by 217 · see citing works
Licht, C. M. M., de Geus, E. J. C., van Dyck, R., & Penninx, B. W. J. H. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181a292a6 · Cited by 215 · see citing works
Longitudinal relationships between workplace bullying and psychological distress
Nielsen, M. B., Hetland, J., Matthiesen, S. B., & Einarsen, S. (2012) · Scandinavian Journal of Work, Environment & Health · doi:10.5271/sjweh.3178 · Cited by 214 · see citing works
Grillon, C., Baas, J. M. P., Cornwell, B., & Johnson, L. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.072 · Cited by 209 · see citing works
The Croonian lectures on evolution and dissolution of the nervous system
Jackson, J. H. (1884) · BMJ · doi:10.1136/bmj.1.1215.703 · Cited by 205 · see citing works
Brosschot, J. F. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.01.004 · Cited by 197 · see citing works
Self-citationHeart rate and heart rate variability changes in the intracarotid sodium amobarbital test
Ahern, G. L., Sollers, J. J., Lane, R. D., Labiner, D. M., Herring, A. M., Weinand, M. E., Hutzler, R., & Thayer, J. F. (2001) · Epilepsia · doi:10.1046/j.1528-1157.2001.042007912.x · Cited by 195 · see citing works
Bar, M., Aminoff, E., Mason, M. F., & Fenske, M. (2007) · Hippocampus · doi:10.1002/hipo.20287 · Cited by 186 · see citing works
Ruiz‐Padial, E., Sollers, J. J., Vila, J., & Thayer, J. F. (2003) · Psychophysiology · doi:10.1111/1469-8986.00032 · Cited by 179 · see citing works
Self-citationAssessing the relationship between rumination and cortisol: a review
Zoccola, P. M., & Dickerson, S. S. (2012) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2012.03.007 · Cited by 178 · see citing works
Brosschot, J. F., Verkuil, B., & Thayer, J. F. (2010) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2010.02.002 · Cited by 176 · see citing works
Self-citationVerkuil, B., Brosschot, J. F., Gebhardt, W. A., & Thayer, J. F. (2010) · Journal of Experimental Psychopathology · doi:10.5127/jep.009110 · Cited by 155 · see citing works
Maier, S. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.09.003 · Cited by 143 · see citing works
Thayer, J. F., & Fischer, J. E. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.02023.x · Cited by 141 · see citing works
Self-citationAdult attachment and the brain
Coan, J. A. (2010) · Journal of Social and Personal Relationships · doi:10.1177/0265407509360900 · Cited by 134 · see citing works
Kuo, T. B. J., Lai, C. J., HUANG, Y., & Yang, C. C. H. (2005) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2005.40656.x · Cited by 134 · see citing works
Melzig, C. A., Weike, A. I., Hamm, A. O., & Thayer, J. F. (2009) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2008.07.013 · Cited by 126 · see citing works
Jarczok, M. N., Kleber, M. E., Koenig, J., Loerbroks, A., Herr, R. M., Hoffmann, K., Fischer, J. E., Benyamini, Y., & Thayer, J. F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117196 · Cited by 121 · see citing works
Self-citationGeneralized anxiety disorder (GAD) as an unsuccessful search for safety
Woody, S., & Rachman, S. (1994) · Clinical Psychology Review · doi:10.1016/0272-7358(94)90040-x · Cited by 115 · see citing works
Christianson, J. P., Benison, A. M., Jennings, J., Sandsmark, E. K., Amat, J., Kaufman, R. D., Baratta, M. V., Paul, E. D., Campeau, S., Watkins, L. R., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4270-08.2008 · Cited by 97 · see citing works
Pappens, M., Schroijen, M., Sütterlin, S., Smets, E., Van den Bergh, O., Thayer, J. F., & Van Diest, I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105054 · Cited by 91 · see citing works
Resting heart rate variability is associated with inhibition of conditioned fear
Wendt, J., Neubert, J., Koenig, J., Thayer, J. F., & Hamm, A. O. (2015) · Psychophysiology · doi:10.1111/psyp.12456 · Cited by 85 · see citing works
Self-citationJarczok, M. N., Li, J., Mauss, D., Fischer, J. E., & Thayer, J. F. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.02.002 · Cited by 79 · see citing works
Self-citationAbuse history is related to autonomic regulation to mild exercise and psychological wellbeing
Dale, L. P., Carroll, L. E., Galen, G., Hayes, J. A., Webb, K. W., & Porges, S. W. (2009) · Applied Psychophysiology and Biofeedback · doi:10.1007/s10484-009-9111-4 · Cited by 78 · see citing works
Jarczok, M. N., Koenig, J., Mauss, D., Fischer, J. E., & Thayer, J. F. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12295 · Cited by 75 · see citing works
Self-citationHeitkemper, M. M., Cain, K. C., Burr, R. L., Jun, S.-E., & Jarrett, M. E. (2011) · Biological Research For Nursing · doi:10.1177/1099800410393274 · Cited by 68 · see citing works
Thayer, J. F., Sollers, J. J., Labiner, D. M., Weinand, M. E., Herring, A. M., Lane, R. D., & Ahern, G. L. (2008) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2008.04.007 · Cited by 64 · see citing works
Self-citationOn the Evolution and Optimality of Mood States
Trimmer, P. C., Paul, E. S., Mendl, M., McNamara, J. M., & Houston, A. I. (2013) · Behavioral Sciences · doi:10.3390/bs3030501 · Cited by 61 · see citing works
Short- and long-term consequences of stressor controllability in adolescent rats
Kubala, K. H., Christianson, J. P., Kaufman, R. D., Watkins, L. R., & Maier, S. F. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.06.027 · Cited by 52 · see citing works
What the Heart Says to the Brain (and vice versa) and Why We Should Listen
Thayer, J. F. (2007) · University of Zagreb University Computing Centre (SRCE) · Cited by 51 · see citing works
Self-citationSmith, R., Allen, J. J. B., Thayer, J. F., & Lane, R. D. (2015) · Biological Psychology · doi:10.1016/j.biopsycho.2015.03.007 · Cited by 49 · see citing works
Self-citationPsychophysiological responses to unpredictable threat: Effects of cue and temporal unpredictability.
Davies, C. D., & Craske, M. G. (2015) · Emotion · doi:10.1037/emo0000038 · Cited by 45 · see citing works
Psychological factors and inflammatory bowel disease: A review of a decade of literature
Searle, A., & Bennett, P. D. (2001) · Psychology Health & Medicine · doi:10.1080/13548500120035382 · Cited by 45 · see citing works
Julius, S. (1995) · Clinical and Experimental Hypertension · doi:10.3109/10641969509087078 · Cited by 37 · see citing works
Thayer, J. F., & Fischer, J. E. (2011) · International Journal of Cardiology · doi:10.1016/j.ijcard.2011.05.058 · Cited by 32 · see citing works
Self-citationOrth-Gomér, K., Wamala, S. P., Horsten, M., Schenck-Gustafsson, K., Schneiderman, N., & Mittleman, M. A. (2000) · JAMA · doi:10.1001/jama.284.23.3008 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Porges, 2004, Neuroception: a subconscious system for detecting threat and safety, Zero to Three: Bull. Natl. Cent. Clin. Infant Progr., 24, 19
Cited by
Sorted by citations
Stress and Health: A Review of Psychobiological Processes
O'Connor, D. B., Thayer, J. F., & Vedhara, K. (2021) · Annual Review of Psychology · doi:10.1146/annurev-psych-062520-122331 · Cited by 948 · see citing works
Self-citationEarly life stress and development: potential mechanisms for adverse outcomes
Smith, K. E., & Pollak, S. D. (2020) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-020-09337-y · Cited by 500 · see citing works
Diamond, L. M., & Alley, J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104720 · Cited by 412 · see citing works
Polyvagal Theory: A Science of Safety
Porges, S. W. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.871227 · Cited by 399 · see citing works
“Others have proposed relationships between safety and stress (Bond et al., 2010; Dollard and McTernan, 2011; Brosschot et al., 2017; Slavich, 2020) that focus on constructs previously explored by the Polyvagal Theory (Porges, 2007).”
BackgroundJarczok, M. N., Weimer, K., Braun, C., Williams, D. P., Thayer, J. F., Gündel, H. O., & Balint, E. M. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104907 · Cited by 246 · see citing works
Self-citationBrosschot, J., Verkuil, B., & Thayer, J. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15030464 · Cited by 244 · see citing works
Self-citationDi Bello, M., Carnevali, L., Petrocchi, N., Thayer, J. F., Gilbert, P., & Ottaviani, C. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.06.016 · Cited by 154 · see citing works
Self-citationCortisol Response to Stress: The Role of Expectancy and Anticipatory Stress Regulation
Pulopulos, M. M., Baeken, C., & De Raedt, R. (2020) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.104587 · Cited by 142 · see citing works
“Social Ties, Health and Wellbeing: A Literature Review and Model”,
Kemp, A. H., Arias, J. A., & Fisher, Z. (2017) · Neuroscience and Social Science · doi:10.1007/978-3-319-68421-5_17 · Cited by 79 · see citing works
Morriss, J., Wake, S., Elizabeth, C., & van Reekum, C. M. (2021) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2021.05.011 · Cited by 52 · see citing works
Hollinsaid, N. L., Pachankis, J. E., Bränström, R., & Hatzenbuehler, M. L. (2023) · Clinical Psychological Science · doi:10.1177/21677026231159050 · Cited by 45 · see citing works
Sensory Sensitivity and Intolerance of Uncertainty Influence Anxiety in Autistic Adults
Normansell-Mossa, K. M., Top, D. N., Russell, N., Freeston, M., Rodgers, J., & South, M. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.731753 · Cited by 45 · see citing works
Gamaiunova, L., Kreibig, S. D., Dan-Glauser, E., Pellerin, N., Brandt, P.-Y., & Kliegel, M. (2022) · Biological Psychology · doi:10.1016/j.biopsycho.2022.108384 · Cited by 37 · see citing works
Lopez, R. B., Brown, R. L., Wu, E.-L. L., Murdock, K. W., Denny, B. T., Heijnen, C., & Fagundes, C. (2020) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000755 · Cited by 36 · see citing works
Wilkie, L., Arroyo, P., Conibeer, H., Kemp, A. H., & Fisher, Z. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.648286 · Cited by 35 · see citing works
Global Adversities, the Media, and Mental Health
Kesner, L., & Horáček, J. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.809239 · Cited by 9 · see citing works
- Authors
- Brosschot, J. F., Verkuil, B., & Thayer, J. F.
- Affiliations
- Leiden University (NL)
- The Ohio State University (US)
- Corresponding author
- Brosschot, Jos F.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 74
- Issue
- Pt B
- Pages
- 287-296
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2502374373
- Cited by
- 178
- References
- 87
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 18 · 2023: 20 · 2022: 26 · 2021: 24 · 2020: 23 · 2019: 16 · 2018: 10 · 2017: 6 · 2016: 2
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- Netherlands Organisation for Health Research and Development (40-00812-98-11029)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- chronic stress, autonomic nervous system activity, contextual conditioning, obesity, aging, loneliness, social networks, occupational stressors
- MeSH terms
- Autonomic Nervous System, Humans, Risk Factors, Stress, Psychological
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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