No / The concepts of “defeat” (representing failed social struggle) and “entrapment” (representing an inability to escape from a situation) have emerged from the animal literature, providing insight into the health consequences of low social rank. Evolutionary models suggest that these constructs co-occur and can lead to the development of mental disorders, although there is limited empirical evidence supporting these predictions. Participants (N=172) were recruited from economically deprived areas in North England. Over half of participants (58%) met clinical cut-offs for depression and anxiety, therefore we conducted analyses to establish whether participant outcomes were dependent on baseline defeat and entrapment levels. Participants completed measures of defeat, entrapment, depression and anxiety at two time-points twelve months apart. Factor analysis demonstrated that defeat and entrapment were best defined as one factor, suggesting that the experiences co-occurred. Regression analyses demonstrated that changes in depression and anxiety between T1 and T2 were predicted from baseline levels of defeat and entrapment; however, changes in defeat and entrapment were also predicted from baseline depression and anxiety. There are implications for targeting perceptions of defeat and entrapment within psychological interventions for people experiencing anxiety and depression and screening individuals to identify those at risk of developing psychopathology.

Background. Recently, 'mental defeat' (MD) has been explored amongst the chronic pain population and considered as a sort of 'self-processing'. Initial research has linked it to anxiety, pain interference and functional disability. Research has recommended that we explore the relationship between MD and other cognitive constructs, such as hopelessness and depression. The present study firstly considers MD as a predictor for pain symptomology and self-efficacy when related cognitive constructs are examined. Secondly, although chronic pain and MD commonly co-occur, causal relationships have yet to be established1. Method. For the cross-sectional analysis, 59 participants from three pain services completed a questionnaire pack assessing five cognitive constructs; anxiety, depression, hopelessness, pain catastrophizing, and mental defeat. Participants also answered questions about their demographics, pain symptomology and self-efficacy. Results. Linear regression analyses revealed that anxiety was most strongly associated with pain symptomology, accounting for 26% of the variance. When breaking down pain symptomology, catastrophizing showed the strongest association with sensory pain, and mental defeat the strongest association with affective pain. Finally, mental defeat was the most strongly associated variable with self-efficacy, accounting for 47% of the variance. Implications. This research has demonstrated the potential importance of assessing mental defeat in chronic pain patients and, where suitable, targeting these feelings during interventions and therapy. This may have an impact on how well people feel able to cope with their pain. Further, the study indicates mental defeat is different to related cognitive constructs involved in pain, such as depression, hopelessness and catastrophizing.

Psychological stressors such as social stress and bullying are prevalent in today’s society. Disorders such as PTSD, depression and social anxiety disorder can be either caused or exacerbated by social stress and treatment options are not always effective in providing relief for these disorders. Our laboratory studies a form of social stress termed conditioned defeat, whereby a defeated Syrian hamster no longer displays species-typical territorial aggression but instead is submissive and defensive toward an intruder in its own cage. We hypothesized that the nucleus accumbens is a necessary component of the circuit mediating the acquisition and expression of conditioned defeat and that dopamine is necessary within the nucleus accumbens for inducing memory processes as well as expression of behavioral responses to stressful situations. We also hypothesized that defeat activates dopaminergic and/or nondopaminergic neurons in the ventral tegmental area (VTA) and that dopamine released by neurons projecting from the VTA to the nucleus accumbens and basolateral amygdala (BLA) increases neuronal activation of these structures during defeat. We found that dopamine, but not GABA, modulates memory of social defeat within the nucleus accumbens. However, GABA does affect the expression of behavioral responses to social defeat. Defeat also increased Fos activation of non-dopaminergic neurons, but it did not increase activation of dopaminergic neurons. Baclofen infusion into the VTA prior to defeat, which was hypothesized to specifically inhibit dopaminergic neurons, did not affect Fos activation within the nucleus accumbens and the basolateral amygdala. These experiments determined that dopamine does modulate memory of social defeat within the nucleus accumbens, but it is currently unclear what the source of this dopamine is. Future experiments are planned to determine this source of dopamine that could be a target of treatment for disorders that are caused or exacerbated by social stress.

Rates of suicidal thoughts and behaviours are heightened amongst prisoners, and present a significant challenge to correctional facilities globally. Despite this, there is a paucity of theoretically driven research examining the factors that underlie suicidality in prisoners. Two theoretical models of suicide, the Cry of Pain model (CoP; Williams, 1997) and the Schematic Appraisals Model of Suicide (SAMS; Johnson, Gooding & Tarrier, 2008) have highlighted the roles of negative appraisals and perceptions of defeat, entrapment, and hopelessness, as key psychological drivers for suicidal thoughts and behaviours. The overarching aim of this thesis was to investigate the psychological mechanisms that underlie suicidal thoughts and behaviours amongst prisoners. A corollary aim was to examine the psychological factors that may confer resilience to suicidal thoughts and behaviours amongst incarcerated individuals. Firstly, a comprehensive narrative review examined evidence of the applicability of current theoretical approaches to suicide, as applied to prisoner samples. The findings of this review highlighted gaps in the literature, from which a number of research questions were developed for investigation in the current thesis. Next, three empirical studies were designed to investigate the roles of perceptions of defeat, entrapment, hopelessness, and negative appraisals in suicidal ideation. In the first of these studies, cross-sectional evidence was obtained that perceptions of internal entrapment and hopelessness were predictive of suicidal ideation amongst prisoners (Chapter 4). In a second study, the predictive effects of defeat, hopelessness, and entrapment were examined in a longitudinal investigation, finding no significant longitudinal relationship (Chapter 7). In a further empirical study, support was provided for the role of momentary negative appraisals of the present and future as proximal predictors of the severity of suicidal thoughts (Chapter 5). Two further studies examined the role of impulsiveness in suicidality, and provided evidence for the deleterious effect of impulsiveness upon both suicidal ideation (Chapter 8) and self-harm ideation (Chapter 9) in prisoners. Two further studies provided the first theoretically driven investigations of potential resilience factors, conceptualized as positive self-appraisals, within a prisoner sample. Based on the Schematic Appraisals Model of Suicide (SAMS), it was proposed that positive self-appraisals would confer resilience against suicidal thoughts and behaviours. Two studies investigated this hypothesis. The first of these studies found that, contrary to predictions, positive self-appraisals of social support and social reciprocity did not buffer the impact of negative situational appraisals upon suicidal thoughts (Chapter 5). In the second study, evidence was obtained for a buffering effect of positive self-appraisals upon suicidal thoughts. In particular, positive appraisals of interpersonal problem-solving were found to buffer the effects of internal entrapment on suicidal thoughts (Chapter 6).Overall, the findings of this thesis serve to further our understanding of the psychological processes underlying the development of, and resilience to, suicidality amongst prisoners. These results underscore the need to empirically examine the applicability and transferability of psychological models of suicide within prisoner populations. Theoretical and clinical implications of these findings are outlined throughout the thesis.

A growing body of research has indicated that the levels of suicidal behaviour are particularly heightened among individuals with Posttraumatic Stress Disorder (PTSD). Two theoretical models of suicide, the Cry of Pain Model of suicide (CoP; Williams, 1997) and the Schematic Appraisals Model of Suicide (SAMS; Johnson, Gooding & Tarrier, 2008) have proposed that perceptions of defeat and entrapment are key components of the psychological mechanisms which drive suicidal behaviour. The SAMS has also emphasized the importance of psychological resilience factors for preventing suicide risk. Resilience to suicide has been recently defined as a set of appraisals which buffer the impact of risk factors on suicidal behaviour. The first aim of this thesis was to investigate the role of perceptions of defeat and entrapment in suicidal behaviour in those with full or subthreshold PTSD. The second aim of this thesis was to obtain empirical evidence for the presence of resilience factors to suicidal behaviour in PTSD. Initially, a comprehensive narrative review and a meta-analysis were conducted to examine the magnitude of the association between various forms of suicidal behaviour and a PTSD diagnosis and the role of comorbid depression in this association. Both, the narrative review and the meta-analysis demonstrated a strong positive association between suicidal behaviour and PTSD, and supported the mediating impact of comorbid depression in this association. A re-analysis of a previous dataset of individuals with PTSD was also pursued to establish the relevance of negative perceptions/appraisals to suicidal behaviour in those with PTSD. Next, three empirical studies were designed to investigate the utility of perceptions of defeat and entrapment in explaining suicidal behaviour in those with full or subthreshold PTSD. The outcomes across the three studies supported the hypothesis that defeat and entrapment represent the proximal psychological drivers of suicidal behaviour in PTSD and fully account for the suicidogenic effects of negative self-appraisals and PTSD symptoms. Two additional empirical studies were conducted to examine resilience factors to suicidal behaviour among individuals with full or subthreshold PTSD. The first of these studies provided evidence that high levels of perceived social support buffered the impact of PTSD symptoms on suicidal behaviour. The last study supported the efficacy of a resilience-boosting technique, the Broad-Minded Affective Coping procedure (BMAC), to enhance the experience of positive emotions and improve mood amongst individuals diagnosed with PTSD. Together, the current results support the SAMS' postulation concerning the role of perceptions of defeat and entrapment in the emergence of suicidal behaviour in PTSD and highlight the importance of boosting resilience as a means of targeting suicidal behaviour in those with PTSD. Clinical implications of these findings are outlined throughout the thesis.

No description available.

Social stress is the most common stressor experienced by humans and exposure to social stress is thought to cause or exacerbate neuropsychiatric illness. Social stress also leads to behavioral and physiological responses in many animal models that closely mirror the symptoms of fear and anxiety in humans. Our laboratory uses Syrian hamsters to study behavioral responses to social stress. Hamsters are highly territorial, but after losing an agonistic encounter, hamsters exhibit a striking behavioral change, abandoning all territorial aggression and instead becoming highly submissive. This behavioral shift is termed conditioned defeat. Epigenetic modifications, such as changes in histone acetylation, are a possible molecular mechanism underlying such behavioral shifts. Histone deacetylase (HDAC) inhibitors have been shown to enhance fear learning and conditioned place preference for drugs of abuse, while suppressing histone acetylation with histone acetyltransferase (HAT) inhibitors impairs long-term memory formation. The first goal of this study was to test the hypothesis that histone acetylation is a molecular mechanism underlying conditioned defeat. We found that animals given an HDAC inhibitor systemically before social defeat later exhibited increased conditioned defeat. This treatment also suppressed defeat-induced immediate-early gene activity in the infralimbic cortex but not the basolateral amygdala. Next, we demonstrated that administration of an HDAC inhibitor in the infralimbic cortex before defeat enhanced stress-induced behavioral responses while HAT inhibition blocked these behavioral changes. Although both males and females exhibit conditioned defeat, the behavioral expression is more pronounced in males. We next used transcriptomic analysis to investigate potential genetic mechanisms leading to this sexually dimorphic expression and to further delineate the role of acetylation in stress-induced behavioral changes. We sequenced the whole brain transcriptome of male and female hamsters as well as the transcriptome of basolateral amygdala, a nucleus necessary for the acquisition and expression of conditioned defeat, of dominant, subordinate, and control animals. Our analysis revealed that numerous genes relating to histone acetylation, including several HDACs, were differentially expressed in animals of different social status and between sexes. Together, these data support the hypotheses that histone modifications underlie behavioral responses to social stress and that some of these modifications are sexually dimorphic.

O estresse é muito presente na vida das pessoas, e grande parte deste é de origem social. O estresse contínuo induz a uma série de efeitos nocivos no organismo. Estes efeitos também podem ser observados no cérebro, principalmente no hipocampo, onde promove alterações na sua morfologia e função. Recentemente, demonstrou-se uma redução do tamanho dos telômeros em leucócitos de mulheres com alto grau de estresse. Os telômeros são seqüências repetitivas dos nucleotídeos TTAGGG, responsáveis por proteger as extremidades dos cromossomos, e sua manutenção e alongamento é mediado, principalmente, pela enzima telomerase. Telômeros e telomerase têm sido alvos de muitos estudos envolvendo o envelhecimento e morte celular. Assim, o presente trabalho estudou os efeitos do estresse psicossocial prolongado em um modelo animal de subjugação/submissão sobre a biologia telomérica do hipocampo. O modelo de subjugação consistiu em um pareamento dos animais experimentais com um camundongo agressivo por 30 minutos. Camundongos machos jovens adultos da linhagem C57BL/6J passaram por este modelo de estresse diariamente por 21 dias. Observou-se um aumento na temperatura corpórea basal em repouso no 21º dia, bem como diminuição na hipertermia reativa a um estresse agudo de manipulação, demonstrando a efetividade do modelo em indução de estresse. Os tamanhos dos telômeros, a expressão gênica da enzima telomerase e sua atividade protéica foram investigados no hipocampo dos camundongos que sofreram o estresse crônico e comparados com animais do grupo controle. Observou-se, após o período de indução do estresse, uma diminuição em aproximadamente 58% no tamanho relativo médio dos telômeros das células hipocampais nos camundongos submetidos ao estresse psicossocial, quando comparados ao grupo controle. A quantidade de RNAm relativo ao gene da telomerase, bem como sua atividade enzimática, mostraram-se similares entre os grupos controle e experimental. Estes resultados sugerem que o estresse psicossocial prolongado reduz o tamanho dos telômeros do hipocampo de camundongos e que esta redução não parece ser devido a alterações gênicas ou enzimáticas da telomerase. Com este estudo procuramos entender melhor os mecanismos celulares e genômicos cerebrais modulados pelo estresse psicológico prolongado, de natureza social. Uma vez que muitos distúrbios psiquiátricos e neurodegenerativos são provenientes do estresse crônico, nossos resultados fornecem mais subsídios para se evidenciar a importância do ambiente social na saúde mental dos indivíduos. / Stressor stimuli are part of the daily life and the major part is derived from the social context. Long term stress can be very harmful, and induce several noxious events in the organism. These effects can also be perceived in the central nervous system, particularly in the hippocampus, in which morphological and functional damages may be observed. Recently a correlation of perceived stress and telomere length was demonstrated in leukocytes of stressed women. Telomeres, which are in tanden repeats of the nucleotides TTAGGG, are responsible to protect the extremities of the chromosomes, and it´s maintenance and elongation is mainly mediated by the enzyme telomerase. Telomeres and telomerase have been the targets of many studies in the last years, concerning aging and cell death. In this regard, the present study has investigated the effects of prolonged psychosocial defeat stress model in the telomeric biology of the hippocampus. Male C57Bl/6J young adult mice were submitted to a 21 days of psychosocial stress. We observed a raise in body temperature, as well as a decrease in reactive hyperthermia to the handling stress, demonstrating the effectiveness of this stress model. The telomere length, the transcript levels of telomerase mRNA, and the activity of the enzyme telomerase were also investigated in the hippocampus of psychosocially stressed mouse. A decrease of 58% in average telomere length was observed in the hippocampal cells of stressed mice when compared to control group. Levels of telomerase mRNA and telomerase activity were similar between control and defeat groups. In this study, we intend to better understand the cellular and genomic mechanisms promoted by long term psychological stress, with social nature, in brain. Since many psychiatric and neurodegenerative disorders have chronic stress underlying them, our results reinforce the importance of the social environment on individual mental health.

O estresse é muito presente na vida das pessoas, e grande parte deste é de origem social. O estresse contínuo induz a uma série de efeitos nocivos no organismo. Estes efeitos também podem ser observados no cérebro, principalmente no hipocampo, onde promove alterações na sua morfologia e função. Recentemente, demonstrou-se uma redução do tamanho dos telômeros em leucócitos de mulheres com alto grau de estresse. Os telômeros são seqüências repetitivas dos nucleotídeos TTAGGG, responsáveis por proteger as extremidades dos cromossomos, e sua manutenção e alongamento é mediado, principalmente, pela enzima telomerase. Telômeros e telomerase têm sido alvos de muitos estudos envolvendo o envelhecimento e morte celular. Assim, o presente trabalho estudou os efeitos do estresse psicossocial prolongado em um modelo animal de subjugação/submissão sobre a biologia telomérica do hipocampo. O modelo de subjugação consistiu em um pareamento dos animais experimentais com um camundongo agressivo por 30 minutos. Camundongos machos jovens adultos da linhagem C57BL/6J passaram por este modelo de estresse diariamente por 21 dias. Observou-se um aumento na temperatura corpórea basal em repouso no 21º dia, bem como diminuição na hipertermia reativa a um estresse agudo de manipulação, demonstrando a efetividade do modelo em indução de estresse. Os tamanhos dos telômeros, a expressão gênica da enzima telomerase e sua atividade protéica foram investigados no hipocampo dos camundongos que sofreram o estresse crônico e comparados com animais do grupo controle. Observou-se, após o período de indução do estresse, uma diminuição em aproximadamente 58% no tamanho relativo médio dos telômeros das células hipocampais nos camundongos submetidos ao estresse psicossocial, quando comparados ao grupo controle. A quantidade de RNAm relativo ao gene da telomerase, bem como sua atividade enzimática, mostraram-se similares entre os grupos controle e experimental. Estes resultados sugerem que o estresse psicossocial prolongado reduz o tamanho dos telômeros do hipocampo de camundongos e que esta redução não parece ser devido a alterações gênicas ou enzimáticas da telomerase. Com este estudo procuramos entender melhor os mecanismos celulares e genômicos cerebrais modulados pelo estresse psicológico prolongado, de natureza social. Uma vez que muitos distúrbios psiquiátricos e neurodegenerativos são provenientes do estresse crônico, nossos resultados fornecem mais subsídios para se evidenciar a importância do ambiente social na saúde mental dos indivíduos. / Stressor stimuli are part of the daily life and the major part is derived from the social context. Long term stress can be very harmful, and induce several noxious events in the organism. These effects can also be perceived in the central nervous system, particularly in the hippocampus, in which morphological and functional damages may be observed. Recently a correlation of perceived stress and telomere length was demonstrated in leukocytes of stressed women. Telomeres, which are in tanden repeats of the nucleotides TTAGGG, are responsible to protect the extremities of the chromosomes, and it´s maintenance and elongation is mainly mediated by the enzyme telomerase. Telomeres and telomerase have been the targets of many studies in the last years, concerning aging and cell death. In this regard, the present study has investigated the effects of prolonged psychosocial defeat stress model in the telomeric biology of the hippocampus. Male C57Bl/6J young adult mice were submitted to a 21 days of psychosocial stress. We observed a raise in body temperature, as well as a decrease in reactive hyperthermia to the handling stress, demonstrating the effectiveness of this stress model. The telomere length, the transcript levels of telomerase mRNA, and the activity of the enzyme telomerase were also investigated in the hippocampus of psychosocially stressed mouse. A decrease of 58% in average telomere length was observed in the hippocampal cells of stressed mice when compared to control group. Levels of telomerase mRNA and telomerase activity were similar between control and defeat groups. In this study, we intend to better understand the cellular and genomic mechanisms promoted by long term psychological stress, with social nature, in brain. Since many psychiatric and neurodegenerative disorders have chronic stress underlying them, our results reinforce the importance of the social environment on individual mental health.

Previous research indicates that serotonin (5-HT) enhances the acquisition of stress-induced changes in behavior; although it is unclear which serotonin receptors mediate this enhancement. 5-HT2 receptors are potential candidates because activation at these receptors is associated with increased fear and anxiety. In this study we investigated whether pharmacological treatments targeting 5-HT2A and 5-HT2C receptors modulated the acquisition and expression of conditioned defeat. Conditioned defeat is a social defeat model in Syrian hamsters (Mesocricetus auratus) that is characterized by increased submissive and defensive behavior and a loss of territorial aggression following social defeat. In experiment 1, we injected the 5-HT2C receptor agonist mCPP (0.3, 1.0, or 3.0 mg/kg) or vehicle prior to social defeat and tested subjects for conditioned defeat behavior in a social interaction test 24 hours later. In experiment 2, subjects received a social defeat, and 24 hours later we injected mCPP (0.3, 1.0, or 3.0 mg/kg) or vehicle prior to a social interaction test. We found that injection of mCPP increased the expression, but not acquisition, of conditioned defeat. In experiment 3, we injected the 5-HT2A receptor antagonist MDL 11,939 (0.5 or 2.0 mg/kg) or vehicle prior to a social defeat and tested subjects for conditioned defeat behavior. In experiment 4, subjects received a social defeat, and 24 hours later we injected MDL 11,939 (0.5 or 2.0 mg/kg) or vehicle prior to a social interaction test. We found that injection of MDL 11,939 significantly decreased the acquisition, but not expression, of conditioned defeat. These data suggest that pharmacological activation of 5-HT2C receptors enhances the expression of conditioned defeat, while pharmacological blockade of 5-HT2A receptors impairs the acquisition of conditioned defeat. These data extend other studies indicating that 5-HT signaling at 5-HT2A receptors facilitate memories for aversive events and 5-HT signaling at 5-HT2C receptors enhance stress-induced anxiety.