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Uncontrollability and Unpredictability in Post-Traumatic Stress Disorder: An Animal Model
Abstract
The disturbances observed in animals subjected to unpredictable and uncontrollable aversive events resemble post-traumatic stress disorder (PTSD) symptoms and thus may constitute an animal model of this disorder. It is argued that the similarity between animals' symptoms and those of trauma victims may reflect common etiological factors. Relevant experiments in which animals exhibit generalized fear and arousal, discrete fear of a conditioned stimulus (CS), analgesia, and avoidance are reviewed with the view that these manifestations may be analogous to the PTSD symptom clusters of persistent arousal, reexperiencing, numbing, and avoidance, respectively. Finally, animal paradigms are suggested to test the validity of the model and specific hypotheses are derived from the animal literature regarding trauma variables that are predictive of particular PTSD symptom clusters.
... Grupe and Nitschke (36) pointed out that a steady environment creates a sense of security, whereas volatile circumstances incubate anxiety. Past studies have also emphasized the strong link between anxiety and the need for control (37)(38)(39)(40). People have cognitive control when they can predict the presence of a threat and assess their ability to respond (41). ...
... People have cognitive control when they can predict the presence of a threat and assess their ability to respond (41). However, when people perceive uncertainty and unpredictability in the present, it would make them feel anxious about the future (39,42). With a similar logic, IoU is tightly wired to FCA as students with higher IoU doubt their ability to eliminate threats in their job search (43). ...
Uncertainty is mushrooming throughout COVID-19, and intolerance of uncertainty (IoU) nudges people into mental health difficulties involving fear, depression, and anxiety. The objective of this study was to investigate the role of depression and fear of COVID-19 (FoC) in the association between IoU and future career anxiety (FCA) among Chinese university students during the COVID-19 pandemic. This study involved 1,919 Chinese undergraduate students from 11 universities in eight Chinese cities with an online self-administered survey that included demographic information, IoU, FoC, depression, and FCA completed by all participants. Our study demonstrated a positive relationship between IoU and FCA and the chain mediation effect of FoC and depression. Thus, understanding how FoC affects FCA not only informs university career professionals and assists students in preparing for employment, but also motivates schools to offer career opportunities workshops and, most importantly, provides mental health support to help students effectively cope with uncertainty and overcome COVID-19-related stress.
... However, stressors are commonly encountered without resulting in permanent or pathological changes. The difference between adaptive and nonadaptive coping and whether stress has temporary or lasting effects can vary with the properties of the stressor, including whether or not it is controllable [6]. ...
Background:
Training with inescapable shock (IS; uncontrollable stressor) is followed by significant decreases in rapid eye movement sleep (REM). However, controllability is important in the effects of stress. We examined the effects of escapable shock (ES; controllable stressor) on sleep and whether the central nucleus of the amygdala (CNA) plays a role in regulating these effects.
Methods:
Six Wistar rats implanted with a cannula located in CNA underwent two days of ES training (20 shock presentations; 0.5 mA; 5.0 s maximum duration; 1.0 min interstimulus interval). Five days later, they were re-exposed to the shock context.
Results:
Following shock training, REM was significantly increased in both light and dark periods. Non-REM (NREM) and total sleep (TS) duration were decreased during the light period. Similar effects on REM and NREM were observed following re-exposure to the training context alone. Microinjections of saline into CNA immediately following ES also produced similar increases in REM, whereas microinjections of muscimol (MUS; GABAA (γ-aminobutyric acid) antagonist) subsequent to ES blocked the increases in REM.
Conclusions:
These data, along with previous work with ES and IS, demonstrate that stressor controllability is important in determining how stress impacts sleep. Moreover, the results of the microinjection study indicate that the effects of ES on REM are regulated through the CNA.
... Results from this study suggest that remaining in a state of prolonged insecurity (compared to experiencing increased security afforded by permanent protection) may be associated with poorer long-term mental health outcomes (Kenny et al., 2022;Law, 2022b). This is consistent with a broader body of research highlighting the importance of a safe, controllable and predictable environment to facilitate mental health recovery following exposure to adversity (Foa et al., 1992;Frazier et al., 2004). We observed a similar pattern for social integration difficulties between groups: refugees who moved from low to high visa security demonstrated significant improvement in social integration problems compared to those who maintained low visa security, which wasn't observed for those that moved from low to medium security visas. ...
Objective
In response to growing numbers of refugees worldwide, host governments are increasingly implementing temporary protection policies; however, little is known regarding the mental health impact of these policies. This online longitudinal study investigated whether refugees who transitioned from low visa security (e.g. short-term transient visas) to medium (e.g. temporary protection visas) or high visa (e.g. permanent visas) security showed changes in depression symptoms, social difficulties and immigration-related fears.
Methods
Participants were 1,201 refugees and asylum-seekers from Arabic, Farsi, Tamil or English-speaking backgrounds. Study variables were measured prior to and after change in visa status (6 months apart).
Results
Refugees who transitioned from low to medium security visas showed reduced immigration-related fear ( B = −0.09, 95% confidence interval = −0.29 to −0.06), but no change in depression symptoms or social difficulties compared to those who retained low visa security. Refugees who transitioned from low to high security visas showed reduced depression symptoms ( B = −0.02, 95% confidence interval = −0.04 to −0.01), social difficulties ( B = −0.04, 95% confidence interval = −0.05 to −0.01) and immigration-related fear ( B = −0.03, 95% confidence interval = −0.06 to −0.01) compared to those who retained low visa security.
Conclusion
Findings indicate that the increased security afforded by temporary protection policies (vs short-term transient visas) did not translate into improved mental health and social outcomes for refugees. In contrast, permanent protection was associated with significant improvements in psychological and social functioning. These results have important policy implications for countries who have committed to protect and facilitate improved mental health among refugees.
... These results should be considered within the context of the perceived controllability of these two stressors. Extensive research indicates that uncontrollable stressors are more detrimental to individuals' well-being, and patterns of coping responses depend on this perceived controllability [23,25,26,52]. In the wake of the ongoing killing of Black people by police and civilians, many of whom are unarmed and perceived as a threat in large part because of their Black identity, self-distraction is likely less advantageous given the uncontrollability of police and White violence. ...
In the same year the world was thrown into turmoil with COVID-19, the USA also experienced a surge in attention given to the plight of Black people in the policing system, following the killing of George Floyd. Both the COVID-19 pandemic and the ongoing "pandemic" of police and White violence against Black people in the USA cause significant amounts of stress, disproportionately affecting Black people. Utilizing qualitative analysis of responses from 128 Black-identifying participants to an online survey, this investigation seeks to understand how the coping strategies of Black people in the USA compare between the racism-related stressor of police killings of Black people and the generalized stressor of the COVID-19 pandemic. Findings demonstrate that while Black people use overlapping strategies to deal with stress, clear patterns exist with regard to differences across racism-related and non-racism-related stressors. We report important implications for understanding the impact of COVID-19 on Black people, cultural understandings of research on coping, and Black mental health more broadly.
... Various studies have demonstrated that controllability, or lack thereof (Foa et al., 1992;Bolstad and Zinbarg, 1997), can have significant impact on the behavioral and physiological outcomes of a stressful event. Uncontrollable stress is linked to negative outcomes and can lead to deficits in associative, motivational, and emotional functioning and can also induce significant alterations in a variety of neurochemical systems (learned helplessness is perhaps the best known experimental effect (e.g., (Seligman et al., 1975;Anisman and Merali, 2009)). ...
Sleep and stress have complex interactions that are implicated in both physical diseases and psychiatric disorders. These interactions can be modulated by learning and memory, and involve additional interactions with the neuroimmune system. In this paper, we propose that stressful challenges induce integrated responses across multiple systems that can vary depending on situational variables in which the initial stress was experienced, and with the ability of the individual to cope with stress- and fear-inducing challenges. Differences in coping may involve differences in resilience and vulnerability and/or whether the stressful context allows adaptive learning and responses. We provide data demonstrating both common (corticosterone, SIH and fear behaviors) and distinguishing (sleep and neuroimmune) responses that are associated with an individual's ability to respond and relative resilience and vulnerability. We discuss neurocircuitry regulating integrated stress, sleep, neuroimmune and fear responses, and show that responses can be modulated at the neural level. Finally, we discuss factors that need to be considered in models of integrated stress responses and their relevance for understanding stress-related disorders in humans.
... It is possible that inappropriate early-life experiences, including a potential lack of socialisation, confinement, stress, and disrupted attachment relationships might have occurred in the laboratories, which produced enduring changes in the brain structure and function (Daskalakis et al. 2013). It is these potential changes which may result in persistent fear responses, fear generalisation, and an inability to extinguish fear (Foa et al. 1992;Beerda et al. 1999;Beerda et al. 2000;McMillan et al. 2015). ...
It is becoming increasingly common for laboratories to allow the rehoming of dogs when they are no longer needed. There is no research, however, comparing the characteristics of dogs from laboratories to dogs acquired from more traditional sources for pets. This study used the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) to compare emotional and behavioural characteristics of 100 former laboratory Beagles who were rehomed to a convenience sample of 244 pet Beagles with no known history of laboratory use. Our results revealed that the former laboratory Beagles exhibited increased fearfulness, attention and attachment behaviours, and more abnormal behaviours than the convenience sample, yet were significantly less aggressive, and likely to chase other animals or escape. Importantly, we also found no significant differences in a majority of the everyday behaviours assessed. Our findings demonstrate dogs rehomed from laboratories form strong bonds with their caregivers, and make equally good companions as their non-laboratory counterparts. Our findings may be helpful in designing appropriate rehabilitation programmes, educating laboratory workers and potential adopters, and support the ongoing efforts to offer these dogs for adoption.
... Thus, animal studies of PTSD in models based on application of electrocutaneous stimulation (ECS) as the stressful traumatizing stimulus are ever more widely used Wotjak, 2006, 2007;Rasmussen et al., 2008;Kung et al., 2010;Careaga et al., 2016]. PTSD models in which the stress stimuli are onetime applications of ECS, although lacking suffi cient ecological correctness, do provide for reproduction of several important features of the traumatizing situation leading to PTSD in humans: the unpredictability and uncontrollability of the situation and variation in the degree of stress-inducing power of the episode over a wide range [Foa et al., 1992]. These models also reproduce many aspects of PTSD symptomatology in humans: signs of emotional blunting [Kung et al., 2010] and social isolation [Louvart et al., 2005], as well as hyperreactivity of novel stimuli and elevated general anxiety levels Li et al., 2006;Kung et al., 2010]. ...
Post-traumatic stress disorder (PTSD) is defined by the International Classification as impairments to emotional state and reactions to a stressful situation in humans. the symptoms of PTSD include anxiety and intrusive memories of the traumatizing event, nightmares, irritability, increased awareness of danger or preoccupation with potential danger, impaired attention, and emotional blunting. The cause of PTSD is an acute psychological trauma induced by a powerful stress-inducing event such as participation in military combat or being in a military combat zone, terrorist acts, natural or technogenic catastrophes, domestic or sexual violence, and the sudden death of a close person, or even health problems. The mechanisms of PTSD have in recent years attracted ever more research attention. Despite great advances in studies of PTSD at the behavioral and psychological, as well as the physiological level, in humans and in a large number of models of PTSD in laboratory animals, the phenomenon of post-traumatic stress disorder remains poorly understood at the theoretical level. This article reviews current concepts of the mechanisms by which PTSD develops, theoretical approaches to understanding this disorder, and experimental data supporting these models.
... The hallmark behavior is the subsequent deficit in escape performance within the shuttle-box apparatus [14,15]. However, rats exposed to the extensive 100 tailshock session also exhibit a wide array of behavioral characteristics that parallel several symptoms of PTSD and depression [16,17]; for review, see [9]. For example, rats that are exposed to 100 tailshocks show anhedonia and lower weight than controls [18][19][20][21]. ...
Exposure to traumatic stress leads to persistent, deleterious behavioral and biological changes in both human and non-human species. The effects of stress are not always consistent, however, as exposure to different stressors often leads to heterogeneous effects. The intensity of the stressor may be a key factor in determining the consequences of stress. While it is difficult to quantify intensity for many stress types, electric shock exposure provides us with a stressor that has quantifiable parameters (presentation length x intensity x number = shock volume). Therefore, to test the procedural differences in shock volume that may account for some reported heterogeneity, we used two common shock procedures. Learned helplessness is a commonly reported behavioral outcome, highlighted by a deficit in subsequent shuttle-box escape, which requires a relatively high-volume stress (HVS) of about 100 uncontrollable shocks. Conversely, stress-enhanced fear learning (SEFL) is another common behavioral outcome that requires a relatively moderate-volume stress (MVS) of only 15 shocks. We exposed rats to HVS, MVS, or no stress (NS) and examined the effects on subsequent fear learning and normal weight gain. We found doubly dissociable effects of the two levels of stress. MVS enhanced contextual fear learning but did not impact weight, while HVS produced the opposite pattern. In other words, more stress does not simply lead to greater impairment. We then tested the hypothesis that the different stress-induced sequalae arouse from an energetic challenge imposed on the hippocampus by HVS but not MVS. HVS rats that consumed a glucose solution did exhibit SEFL. Furthermore, rats exposed to MVS and glucoprivated during single-trial context conditioning did not exhibit SEFL. Consistent with the hypothesis that the inability of HVS to enhance fear learning is because of an impact on the hippocampus, HVS did enhance hippocampus-independent auditory fear learning. Finally, we provide evidence that stressors of different volumes produce dissociable changes in glutamate receptor proteins in the basolateral amygdala (BLA) and dorsal hippocampus (DH). The data indicate that while the intensity of stress is a critical determinant of stress-induced phenotypes that effect is nonlinear.
Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining a novel uncertain shock anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we trained a brain model that accurately predicted the intensity of subjective experience of anxious arousal on the population and individual level. In a series of analyses utilizing available fMRI datasets, we further demonstrate that the signature specifically predicted anxious anticipation and was not sensitive in predicting pain, general anticipation or unspecific arousal. The signature was functionally and spatially distinguishable from representations of subjective fear or negative affect. We developed a sensitive, generalizable, and specific neuromarker for subjective anxious arousal experienced during uncertain threat anticipation that can facilitate model development and clinical translation.
Recently, a five-session Processing of Positive Memories Technique (PPMT) was proposed as a novel intervention for posttraumatic stress disorder (PTSD). One purported outcome of and mechanism underlying PPMT's effects on PTSD is improved positive affect processes. In this uncontrolled pilot study, we examined whether PPMT was associated with decreases in PTSD severity; and whether changes in positive affect levels, reactivity, and dysregulation related to changes in PTSD severity across sessions. The sample included 16 trauma-exposed participants seeking services at a University Psychology Clinic (Mage=27.44 years; 68.80% women). Multilevel linear growth models examined the main effects of each positive affect variable and their interactions with time on PTSD severity. PTSD severity decreased across PPMT treatment in each model (bs=-0.43 to -0.33; d=-0.03; ps<.001-0.008). There was a main effect of positive emotion dysregulation (b=1.16, d=0.11; p=0.009), but not of positive affect levels (p=0.821) or reactivity (p=0.356) on PTSD severity. However, positive affect processes did not modify the trajectory of PTSD severity across treatment. Regarding PTSD symptom clusters, there was an interaction between positive affect levels and time on alterations in arousal and reactivity (AAR) cluster severity (b=-0.01, p=0.036); individuals with positive affect levels 1 SD above the mean (b=-0.18, p<0.01) and at the mean (b=-0.10, p=0.01) had greater decreases in AAR cluster severity across treatment compared to individuals with positive affect levels 1 SD below the mean (b=-0.02, p=0.710). Findings suggest that PPMT may relate to improved PTSD symptoms; and that positive affect levels/dysregulation may be worthwhile targets for future investigations.
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