The chronic social defeat stress model has been instrumental in shaping our understanding of neurobiology relevant to affect-related illnesses, including major depressive disorder. However, the ...classic chronic social defeat stress procedure is limited by its exclusive application to adult male rodents. We have recently developed a novel vicarious social defeat stress procedure wherein one mouse witnesses the physical defeat bout of a conspecific from the safety of an adjacent compartment. This witness mouse develops a similar behavioral phenotype to that of the mouse that physically experiences social defeat stress, modeling multiple aspects of major depressive disorder. Importantly, this new procedure allows researchers to perform vicarious social defeat stress in males or females and in juvenile mice, which typically are excluded from classic social defeat experiments. Here we discuss several recent advances made using this procedure and how its application provides a new preclinical approach to study the neurobiology of psychological stress-induced phenotypes.
Hearing voices is a common and often distressing experience for people with psychosis, and many individuals experience medication-resistant auditory verbal hallucinations (AVH). Psychosocial ...interventions are often employed to address distress over hearing voices. However, although links have been made between adverse social experiences and psychosis broadly, no work has yet delineated the relationship between day-to-day social stress and hallucination severity. We aimed to define that relationship in both clinical and non-clinical voice-hearers.
A sample of 278 participants with a history of hearing voices was selected from the Yale Control Over Perceptual Experiences (COPE) Project. They were administered self-report measures of recent stress and recent auditory experiences within a cross-sectional design. Regression models were used to evaluate whether self-reported aspects of recent stress—and social stress in particular—were related to recent frequency of and distress over hearing voices. Related demographics and clinical characteristics were included as covariates.
A significant relationship was observed between recent social stress and both recent frequency of and distress over hearing voices. While other aspects of recent stress were also related to recent distress over voices, social stressors uniquely predicted distress over voice-hearing, beyond the influence of other stressors. Depressive symptom severity was also related to distress over voices.
Results suggest that daily social stress may be an important consideration and a potential treatment target for individuals experiencing clinical distress over auditory hallucinations.
Chronic psychosocial stress stands as a significant heterogeneous risk factor for psychiatric disorders. The brain’s physiological response to such stress varies based on the frequency and intensity ...of stress episodes. However, whether stress episodes divergently could affect hippocampal cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling remains unclear, a key regulator of psychiatric symptoms. We aimed to assess how two distinct patterns of social defeat stress exposure impact anxiety- and depression-like behaviors, fear, and hippocampal CREB-BDNF signaling in adult male rats. To explore this, adult male Sprague-Dawley rats were subjected to psychosocial stress using a Resident/Intruder paradigm for ten consecutive days (continuous social defeat stress: CS) or ten social defeat stress over the course of 21 days (intermittent social defeat stress IS). Behavioral tests (including novelty-suppressed feeding test, forced swimming test, and contextually conditioned fear) were conducted. Protein expression levels of phosphorylated CREB and BDNF in the dorsal and ventral hippocampi were examined. CS led to heightened anxiety-like behavior, fear, and increased levels of phosphorylated CREB in both the dorsal and ventral hippocampi. Conversely, IS resulted in increased anxiety-like behavior and behavioral despair alongside decreased levels of phosphorylated CREB and BDNF, particularly in the dorsal hippocampus. These findings indicate that chronic psychosocial stress divergently affects hippocampal CREB-BDNF signaling and emotional regulation depending on the stress episode. Such insights could enhance our understanding of the molecular basis of the heterogeneity of psychiatric disorders and facilitate the development of innovative treatment approaches to patients with psychiatric disorders.
The social defeat stress model is commonly used to study depression and anxiety disorder, which can significantly affect the structure and function of neurons in the hippocampus; however, the ...relevant mechanism in neuronal loss has not been clearly defined. In the present study, a social defeat stress model was established in mice to evaluate the impact of social defeat stress on the structure of neurons in the hippocampus using Western blotting, immunofluorescence, Nissl staining, Golgi staining and transmission electron microscopy. The results demonstrated that social defeat stress leads to disruption of homeostasis in the hippocampus and the integrity of mitochondria in hippocampal neurons was markedly affected by enhanced mitophagy and autophagy resulting in inhibition of development and growth. These findings provide new insights into the mechanisms of neuronal development and growth due to social defeat stress, which should help in the development of new strategies to combat the effects of depression and anxiety disorder.
•Social defeat stress leads to disruption of homeostasis in the hippocampus.•The integrity of neuronal in hippocampi CA1 and CA3 region was destroyed after Social defeat stress.•Social defeat stress resulting in inhibition of development and growth through mitophagy and autophagy.
•Stress susceptible but not resilient male and female mice showed prolonged mechanical hypersensitivity following arthritis.•Arthritis-associated hypersensitivity was exacerbated in susceptible male ...but not female mice.•Susceptible male but not female mice presented microgliosis and monocyte infiltration in the ACC following arthritis.•Blood Ly6Chigh monocytes were increased in susceptible male but not female mice.•Ly6Chigh monocyte depletion abrogated the prolonged hypersensitivity and associated brain changes in susceptible male mice.
Chronic stress enhances the risk of neuropsychiatric disorders and contributes to the aggravation and chronicity of pain. The development of stress-associated diseases, including pain, is affected by individual vulnerability or resilience to stress, although the mechanisms remain elusive. We used the repeated social defeat stress model promoting susceptible and resilient phenotypes in male and female mice and induced knee mono-arthritis to investigate the impact of stress vulnerability on pain and immune system regulation. We analyzed different pain-related behaviors, measured blood cytokine and immune cell levels, and performed histological analyses at the knee joints and pain/stress-related brain areas. Stress susceptible male and female mice showed prolonged arthritis-associated hypersensitivity. Interestingly, hypersensitivity was exacerbated in male but not female mice. In males, stress promoted transiently increased neutrophils and Ly6Chigh monocytes, lasting longer in susceptible than resilient mice. While resilient male mice displayed persistently increased levels of the anti-inflammatory interleukin (IL)-10, susceptible mice showed increased levels of the pro-inflammatory IL-6 at the early- and IL-12 at the late arthritis stage. Although joint inflammation levels were comparable among groups, macrophage and neutrophil infiltration was higher in the synovium of susceptible mice. Notably, only susceptible male mice, but not females, presented microgliosis and monocyte infiltration in the prefrontal cortex at the late arthritis stage. Blood Ly6Chigh monocyte depletion during the early inflammatory phase abrogated late-stage hypersensitivity and the associated histological alterations in susceptible male mice.
Thus, recruitment of blood Ly6Chigh monocytes during the early arthritis phase might be a key factor mediating the persistence of arthritis pain in susceptible male mice. Alternative neuro-immune pathways that remain to be explored might be involved in females.
•Stressful experiences can be transmitted among individuals through social interactions.•Rodent studies of vicarious social defeat stress and social defeat stress crossover are reviewed.•The ...vicarious experience of social defeat is associated with a host of physiological and behavioral deficits.•Social interaction with a stressed partner in the aftermath of social defeat elicits stress responses.•These models can be useful for studying the neurobiological processes underlying the contagion of stress across individuals.
Stressful experiences can be transmitted among individuals through social interactions. Like humans, rodents are social creatures whose behavior and physiology can be influenced by the emotional state of fellow rodents. This paper will review rodent studies which have explored two conditions of potential social stress contagion using the social defeat paradigm. In the vicarious social defeat model, mice and rats that witness a conspecific being socially defeated exhibit physiological stress responses and develop a host of depressive- and anxiety-like behavioral deficits. Likewise, social interaction with a stressed partner in the aftermath of social defeat stress results in physiological stress responses and social avoidance behavior. After summarizing the existing literature on this newly emerging area of social defeat stress contagion in rodents, we will discuss the potential utility of these rodent models for investigating the neurobiological processes and sensory channels of information that allow for the spread of psychophysiological effects of stress across individuals.
Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used models to study the physiological mechanisms and behavioral outcomes of this type of ...stress is chronic defeat stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, non-stressed animals were housed in groups. The cluster analysis of the behavioral profile displayed during the first social interaction divided subjects into two groups: active/aggressive (AA) and passive/reactive (PR). The day after the end of the stress period, the following behavioral analyses were performed: the sucrose preference test (SPT) on day 19, the open field test (OFT) on day 20, and the forced swim test (FST) on day 21. Immediately after completing the last test, animals were weighed, and blood samples were obtained. Then, they were sacrificed, and their prefrontal cortices and hippocampi were removed and stored to analyze monoamine levels. Stressed animals displayed anhedonia, and solely the PR mice continued to show higher levels of immobility in the OFT and FST. All stressed animals, regardless of the coping strategy, presented higher plasma corticosterone levels. In addition, stressed mice showed lower levels of tyrosine, dopamine, DOPAC, MHPG, kynurenine, kynurenic acid, and 5-HIAA levels but higher serotonin levels in the prefrontal cortex, not in the hippocampus. In conclusion, our results show that CSD induces differences in monoamine levels between brain areas, and these differences did not respond to the coping strategy adopted.
Despite the twofold higher prevalence of major depressive and posttraumatic stress disorders in women compared with men, most clinical and preclinical studies have focused on male subjects. We used ...an ethological murine model to study several cardinal symptoms of affective disorders in the female targets of female aggression.
Intact Swiss Webster (CFW) female resident mice were housed with castrated male mice and tested for aggression toward female intruders. For 10 days, aggressive CFW female residents defeated C57BL/6J (B6) female intruders during 5-minute encounters. Measures of corticosterone, c-Fos activation in hypothalamic and limbic structures, and species-typical behaviors were collected from defeated and control females. Ketamine (20 mg/kg) was tested for its potential to reverse stress-induced social deficits.
Housed with a castrated male mouse, most intact resident CFW females readily attacked unfamiliar B6 female intruders, inflicting >40 bites in a 5-minute encounter. Compared with controls, defeated B6 females exhibited elevated plasma corticosterone and increased c-Fos activation in the medial amygdala, ventral lateral septum, ventromedial hypothalamus, and hypothalamic paraventricular nucleus. Chronically defeated females also showed vigilance-like behavior and deficits in social interactions, novel object investigation, and nesting. The duration of social interactions increased 24 hours after chronically defeated female mice received a systemic dose of ketamine.
These findings demonstrate that CFW female mice living with male conspecifics can be used as aggressive residents in an ethological model of female social defeat stress. These novel behavioral methods will encourage further studies of sex-specific neural, physiological, and behavioral adaptations to chronic stress and the biological bases for interfemale aggression.
Suicidal behaviour poses a significant public health concern. Research into the factors that distinguish between the emergence of suicide ideation and the enactment of a suicide attempt is crucial. ...This study tests central tenets of the Integrated Motivational-Volitional Model of suicidal behaviour (IMV, O’Connor and Kirtley, 2018) which posits that volitional phase factors govern the transition from thinking to attempting suicide. 299 adults completed a face-to-face interview and were allocated to groups based on their suicidal history: Suicide attempt group (N = 100), suicide ideation group (N = 105), and a control group (N = 94). Measures were taken at baseline, at 1-month and 6-months follow-up. As predicted, the attempt group differed from the ideation group on all volitional phase factors. Those who had attempted suicide reported higher capability for suicide, were more likely to have a family member or friend who had self-injured or attempted suicide, and were more impulsive. In keeping with the IMV model, the ideation and attempt groups had similar scores on the motivational factors. Defeat and entrapment were significant predictors of ideation at baseline, and mediation analyses indicated that defeat had an indirect effect on ideation through entrapment at baseline and at 1-month follow-up. The results support the IMV model and suggest that entrapment should be routinely included in suicide risk assessments. Further research to test predictors of the transition from suicide ideation to suicide attempts is crucial to inform future intervention development and health care delivery.
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