Traits of fear resistance and susceptibility in an advanced intercross line

Genetic variability in the strength and precision of fear memory is hypothesised to contribute to the etiology of anxiety disorders, including post-traumatic stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R) phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J inbred mice by selective breeding. We identified specific traits underlying individual variability in Pavlovian conditioned fear learning and memory. Offspring of selected lines differed in the acquisition of conditioned fear. Furthermore, F-S mice showed greater cued fear memory and generalised fear in response to a novel context than F-R mice. F-S mice showed greater basal corticosterone levels and hypothalamic corticotrophin-releasing hormone (CRH) mRNA levels than F-R mice, consistent with higher hypothalamic-pituitary-adrenal (HPA) axis drive. Hypothalamic mineralocorticoid receptor and CRH receptor 1 mRNA levels were decreased in F-S mice as compared with F-R mice. Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate basal levels of brain activity. MEMRI identified a pattern of increased brain activity in F-S mice that was driven primarily by the hippocampus and amygdala, indicating excessive limbic circuit activity in F-S mice as compared with F-R mice. Thus, selection pressure applied to the AIL population leads to the accumulation of heritable trait-relevant characteristics within each line, whereas non-behaviorally relevant traits remain distributed. Selected lines therefore minimise false-positive associations between behavioral phenotypes and physiology. We demonstrate that intrinsic differences in HPA axis function and limbic excitability contribute to phenotypic differences in the acquisition and consolidation of associative fear memory. Identification of system-wide traits predisposing to variability in fear memory may help in the direction of more targeted and efficacious treatments for fear-related pathology. Through short-term selection in a B6D2 advanced intercross line we created mouse populations divergent for the retention of Pavlovian fear memory. Trait distinctions in HPA-axis drive and fear network circuitry could be made between naïve animals in the two lines. These data demonstrate underlying physiological and neurological differences between Fear-Susceptible and Fear-Resistant animals in a natural population. F-S and F-R mice may therefore be relevant to a spectrum of disorders including depression, anxiety disorders and PTSD for which altered fear processing occurs.

Pavlovian fear memory circuits and phenotype models of PTSD

Pavlovian fear conditioning, also known as classical fear conditioning is an important model in the study of the neurobiology of normal and pathological fear. Progress in the neurobiology of Pavlovian fear also enhances our understanding of disorders such as posttraumatic stress disorder (PTSD) and with developing effective treatment strategies. Here we describe how Pavlovian fear conditioning is a key tool for understanding both the neurobiology of fear and the mechanisms underlying variations in fear memory strength observed across different phenotypes. First we discuss how Pavlovian fear models aspects of PTSD. Second, we describe the neural circuits of Pavlovian fear and the molecular mechanisms within these circuits that regulate fear memory. Finally, we show how fear memory strength is heritable; and describe genes which are specifically linked to both changes in Pavlovian fear behavior and to its underlying neural circuitry. These emerging data begin to define the essential genes, cells and circuits that contribute to normal and pathological fear.

Recovering from the earthquake : early childhood teachers and children collaboratively telling stories about their experiences

Purpose – Traumatic events can cause post-traumatic stress disorder due to the severity of the often unexpected events. The purpose of this paper is to reveal how conversations around lived experiences of traumatic events, such as the Christchurch earthquake in February 2011, can work as a strategy for people to come to terms with their experiences collaboratively. By encouraging young children to recall and tell of their earthquake stories with their early childhood teachers they can begin to respond, renew, and recover (Brown, 2012), and prevent or minimise more stress being developed. Design/methodology/approach – The study involved collecting data of the participating children taking turns to wear a wireless microphone where their interactions with each other and with teachers were video recorded over one week in November 2011. A total of eight hours and 21 minutes of footage was collected; four minutes and 19 seconds of that footage are presented and analysed in this paper. The footage was watched repeatedly and transcribed using conversation analysis methods (Sacks, 1995). Findings – Through analysing the detailed turn-taking utterances between teachers and children, the orderliness of the co-production of remembering is revealed to demonstrate that each member orients to being in agreement about what actually happened. These episodes of story telling between the teachers and children demonstrate how the teachers encourage the children to tell about their experiences through actively engaging in conversations with them about the earthquake. Originality/value – The conversation analysis approach used in this research was found to be useful in investigating aspects of disasters that the participants themselves remember as important and real. This approach offers a unique insight into understanding how the earthquake event was experienced and reflected on by young children and their teachers, and so can inform future policy and provision in post-disaster situations.

Health and safety for clean-up and recovery workers

This paper will identify and discuss the major occupational health and safety (OHS) hazards and risks for clean-up and recovery workers. The lessons learned from previous disasters including; the Exxon Valdez oil spill, World Trade Centre (WTC) terrorist attack, Hurricane Katrina and the Deepwater Horizon Gulf of Mexico oil spill will be discussed. The case for an increased level of preparation and planning to mitigate the health risks for clean-up and recovery workers will be presented, based on recurring themes identified in the peer reviewed literature. There are a number of important issues pertaining to the occupational health and safety of workers who are engaged in clean-up and recovery operations following natural and technological disasters. These workers are often exposed to a wide range of occupational health and safety hazards, some of which may be unknown at the time. It is well established that clean-up and recovery operations involve risks of physical injury, for example, from manual handling, mechanical equipment, extreme temperatures, slips, trips and falls. In addition to these well established physical injury risks there are now an increasing number of studies which highlight the risks of longer term or chronic health effects arising from clean-up and recovery work. In particular, follow up studies from the Exxon Valdez oil spill, Hurricane Katrina and the World Trade Centre (WTC) terrorism attack have documented the longer term health consequences of these events. These health effects include respiratory symptoms and musculoskeletal disorders, as well as post traumatic stress disorder (PTSD). In large scale operations many of those workers and supervisors involved have not had any specific occupational health and safety (OHS) training and may not have access to the necessary instruction, personal protective equipment or other appropriate equipment, this is especially true when volunteers are used to form part of the clean-up and recovery workforce. In general, first responders are better equipped and trained than clean-up and recovery workers and some of the training approaches used for the traditional first responders would be relevant for clean-up and recovery workers.

Brave New World of Health

"Within contemporary society the meaning of 'health' is surprisingly unstable. Guiding principles that once seemed self-evident have been challenged by new social, scientific and economic forces. This book argues that the foundational terms and concepts, which form the basic building blocks of dialogue about health, are now in flux. While the forces in play differ, and the pace of change is varied, there is now a 'brave new world' of health which characterises policy debate about health (and illness or disability). This permeates even the more narrow technical issues within clinical medicine, the law and medical science. This construction and reconstruction of health has important implications for the development of law and policy. The book draws on international and local experts to explore these issues. It opens with consideration of the economic and social forces of 'globalisation' - the macro level forces which now shape the 'lived realities' of health for the world's people. This is then contextualised through a series of detailed 'case studies' of more localised examples including; pharmaceuticals, preimplantation genetic diagnosis, body modification, abortion, anorexia and post-traumatic stress disorder. The book also interrogates the way modern health research influences public conceptions of health. Across these issues the book canvasses the social forces at work in the construction of health, disability and illness in shaping our understandings of such concepts by the public, by individuals, by the courts, and by international bodies. Brave New World of Health is an important contribution to advancing that understanding."--Publisher's website.

Promoting posttraumatic growth in police recruits : preliminary results of a randomised controlled resilience intervention trial

Recent research has demonstrated that the same experiences that may elicit symptoms of post-traumatic stress disorder (PTSD) in emergency service personnel can also provide a catalyst for positive personal changes such as posttraumatic growth (PTG). In this research newly recruited police officers (N = 412) participated in a randomised control trial of a program specifically designed to promote mental health. On entry to the academy, new recruits were randomly allocated, by classrooms, to either a treatment as usual condition (i.e., existing psychoeducation program) or to the intervention group. The Promoting Resilient Officers (PRO) program is a resilience building intervention adapted from an earlier resilience building program in collaboration with the police service. The PRO program also includes additional components on trauma and PTG. The current research included the participants who had experienced trauma prior to or during the research period (N = 246). It was hypothesised that participation in the PRO program would increase levels of PTG and lower levels of PTSD when compared to recruits in the control condition. Using multilevel modelling and post-hoc analyses, results indicated there were significantly higher levels of PTG across multiple dimensions when compared to the control group. There was no effect on PTSD symptoms with both conditions showing a floor effect. The research indicated the potential value of developing interventions that elicit reflections on the potential for positive as well as negative outcomes of experiencing traumatic and other highly challenging events.

Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

The impact that stressful encounters have upon long-lasting behavioural phenotypes is varied. Whereas a significant proportion of the population will develop "stress-related" conditions such as post-traumatic stress disorder or depression in later life, the majority are considered "resilient" and are able to cope with stress and avoid such psychopathologies. The reason for this heterogeneity is undoubtedly multi-factorial, involving a complex interplay between genetic and environmental factors. Both genes and environment are of critical importance when it comes to developmental processes, and it appears that subtle differences in either of these may be responsible for altering developmental trajectories that confer vulnerability or resilience. At the molecular level, developmental processes are regulated by epigenetic mechanisms, with recent clinical and pre-clinical data obtained by ourselves and others suggesting that epigenetic differences in various regions of the brain are associated with a range of psychiatric disorders, including many that are stress-related. Here we provide an overview of how these epigenetic differences, and hence susceptibility to psychiatric disorders, might arise through exposure to stress-related factors during critical periods of development.

A high and low fear phenotype mouse model

Fear-related illnesses such as post-traumatic stress disorder (PTSD) impose a tremendous burden on individual quality of life, families, and the national economy. In the military population, 17-20% of services members returning from deployment are diagnosed with PTSD. While treatments have improved for PTSD and are helpful for some, many people continue to suffer despite therapy. The aim of this research is to examine fear memory behaviourally and at the cellular level in the amygdala by using a unique inter-cross strain of high and low fear phenotype mice. An extended outcross C57BL/6J x DBA/2J (F8) are selected for high or low Pavlovian fear memory to context and cue. On presentation of either the original learning context or the cue (tone) mice display high or low levels of freezing as a behavioural measure of fear. In order to identify key aspects of the cellular basis of this difference in fear memory behaviour we are making measurements of protein levels and neuron numbers of a known pathway involved in the consolidation of a long term fear memory (pMAPK). Ongoing studies aim to determine if high fear behaviour is associated with differential signalling in the lateral amygdala compared to low fear behaviour. Additionally, by blocking this pathway in the lateral amygdala (LA), we aim to reduce fear behaviour following Pavlovian fear conditioning. This research will help to unravel the cellular mechanisms underlying high fear behaviour and advance the field toward targeted treatment and improved outcomes, ultimately improving human quality of life.

Barbara's story : a thematic analysis of a relative's reflection of being in the intensive care unit

Aim The aim of this reflective account is to provide a view of the intensive care unit (ICU) relative’s experiences of supporting and being supported in the ICU. Background Understanding the relatives’ experiences of ICU is important especially because a recent work has identified the potential for this group to develop post-traumatic stress disorder, a condition that is normally equated with the ICU survivor. Design A thematic analysis was used in identifying emerging themes that would be significant in an ICU nursing context. Setting The incident took place in two 8-bedded ICUs (Private and National Health Service) in October. Results Two emergent themes were identified from the reflective story – fear of the technological environment and feeling hopeless and helpless. Conclusion The use of relative stories as an insight into the live experiences of ICU relatives may give a deeper understanding of their life-world. The loneliness, anguish and pain of the ICU relative extends beyond the walls of the ICU, and this is often negated as the focus of the ICU team is the patient. Relevance to clinical practice: Developing strategies to support relatives might include the use of relative diaries used concurrently with patient diaries to support this groups recovery or at the very least a gaining a sense of understanding for their ICU experience. Relative follow-up clinics designed specifically to meet their needs where support and advice can be given by the ICU team, in addition to making timely and appropriate referrals to counselling services and perhaps involving spiritual leaders where appropriate.

High and low fear phenotypes show differences in phosphorylated (p44/42 ERK) MAPK-expressing neurons in the lateral amygdala

Post traumatic stress disorder (PTSD) is a serious medical condition effecting both military and civilian populations. While its etiology remains poorly understood it is characterized by high and prolonged levels of fear responding. One biological unknown is whether individuals expressing high or low conditioned fear memory encode the memory differently and if that difference underlies fear response. In this study we examined cellular mechanisms that underlie high and low conditioned fear behavior by using an advanced intercrossed mouse line (B6D2F1) selected for high and low Pavlovian fear response. A known requirement for consolidation of fear memory, phosphorylated mitogen activated protein kinase (p44/42 (ERK) MAPK (pMAPK)) in the lateral amygdala (LA) is a reliable marker of fear learning-related plasticity. In this study, we asked whether high and low conditioned fear behavior is associated with differential pMAPK expression in the LA and if so, is it due to an increase in neurons expressing pMAPK or increased pMAPK per neuron. To examine this, we quantified pMAPK-expressing neurons in the LA at baseline and following Pavlovian fear conditioning. Results indicate that high fear phenotype mice have more pMAPK-expressing neurons in the LA. This finding suggests that increased endogenous plasticity in the LA may be a component of higher conditioned fear responses and begins to explain at the cellular level how different fear responders encode fear memories. Understanding how high and low fear responders encode fear memory will help identify novel ways in which fear-related illness risk can be better predicted and treated.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Assessment of flood-related mental illness in Bangladesh

This thesis assessed the mental health impacts of flooding and explored the key determinants of flood-related mental illness in the coastal region of Bangladesh. This study found significant increase in the prevalence of mental illness after flooding. Flood-exposure and socio-economic factors were significantly associated with post-flood mental illness. These findings may help the policy-makers to improve the early intervention and screening programs and may also have significant public health implications in the control and prevention of flood-related mental illness in Bangladesh.

The impact of personality and workplace belongingness on mental health workers’ professional quality of life

Objectives Mental health workers are constantly exposed to their clients’ stories of distress and trauma. While listening to these stories can be emotionally draining, professionals in this field still derive pleasure from their work. This study examined the role of personality and workplace belongingness in predicting compassion satisfaction, secondary traumatic stress, and burnout in mental health professionals. Methods Mental health staff (N = 156) working in a counselling service completed a questionnaire that included measures relating to professional quality of life, the Five-Factor Model of personality, workplace belongingness, as well as questions relating to the participants’ demographic profile, work roles and trauma history. Results The results indicated that, high levels of emotional stability (low neuroticism), extraversion, agreeableness, conscientiousness, and being connected at work, are essential factors that promote the professional quality of life of mental health workers. Specifically, workplace belongingness was the strongest predictor of compassion satisfaction and low levels of burnout, while neuroticism was the strongest predictor of secondary traumatic stress. Conclusions Important implications from this study include: (1) encouraging mental health staff to increase self-awareness of their dispositional characteristics and how their personalities affect their wellbeing at work, and; (2) encouraging management to facilitate practices where mental health workers feel connected, respected, and supported in their organisation.

LGBTIQ experiences in the workforce

The experience of lesbian, gay, bisexual, transgender, intersex and queer (LGBTIQ) health consumers has, in the last decade, gained attention and is now recognised as one of the social determinants of health. Our recent meta-synthesis on the experiences of LGBTIQ health and medical professionals demonstrated that they are susceptible to higher levels of anxiety and depression partially due to lack of acceptance in their workplace. The paramedic workforce is known to be a high risk occupational group for post-traumatic stress disorder and depression. Theoretically, LGBTIQ paramedics working in a heteronormative culture may experience increased level of discrimination and stress than their heterosexual colleagues. The integration of LGBTIQ into the paramedic workforce is unfeatured in our systematic review. While LGBTIQ health professionals receive legislative protection against discrimination, discrimination still exists in practice through lack of visibility. There is a common misconception that LGBTIQ is a homogenous group with equal needs. Effective and efficient integration of LGBTIQ health professionals could improve workplace satisfaction, workforce retention, and equity of access by marginalised groups.

Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia

BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP). METHODS: Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models. RESULTS: Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations. CONCLUSION: These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity