KPNA3 variation is associated with schizophrenia, major depression, opiate dependence and alcohol dependence

KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.

Predicting posttraumatic growth and posttraumatic stress in fire-fighters

Emergency service workers (e.g., fire-fighters, police and paramedics) are exposed to elevated levels of potentially traumatising events through the course of their work. Such exposure can have lasting negative consequences (e. g., Post Traumatic Stress Disorder; PTSD) and/or positive outcomes (e. g., Posttraumatic Growth; PTG). Research had implicated trauma, occupational and personal variables that account for variance in post-trauma outcomes yet at this stage no research has investigated these factors and their relative influence on both PTSD and PTG in a single study. Based in Calhoun and Tedeschi’s (2013) model of PTG and previous research, in this study regression models of PTG and PTSD symptoms among 218 fire-fighters were tested. Results indicated organisational factors predicted symptoms of PTSD, while there was partial support for the hypothesis that coping and social support would be predictors of PTG. Experiencing multiple sources of trauma, higher levels of organisational and operational stress, and utilising cognitive reappraisal coping, were all significant predictors of PTSD symptoms. Increases in PTG were predicted by experiencing trauma from multiple sources and the use of self-care coping. Results highlight the importance of organisational factors in the development of PTSD symptoms, and of individual factors for promoting PTG.

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.

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.

PTSD and traumatic stress : from gene to community and bench to bedside

Individuals and communities are exposed to traumatic events, those that are accidents or naturally occurring and those that are intentional or human made. Although resilience is the expected response, for some, posttraumatic stress disorder may be the outcome. Brain models of PTSD require understanding the phenomenology of the disorder and the brain “break down” that occurs. Among several models, importantly, is the perspective that PTSD is a “forgetting” disorder. Other elements in the onset and triggers of PTSD can identify further models to examine at the bench. New studies of the 5-HT2A receptor, the glucocorticoid receptor, p11, mitochondrial genes and cannabinoids are bringing new perspectives to understanding brain function in PTSD. Effective treatments indicate areas for bench research on the mechanisms of the disorder.

A critical evaluation of written discharge advice for people with mild traumatic brain injury : what should we be looking for?

Objective: To formally evaluate the written discharge advice for people with mild traumatic brain injury (mTBI). Methods: Eleven publications met the inclusion criteria: (1) intended for adults; (2) ≤two A4 pages; (3) published in English; (4) freely accessible; and (5) currently used (or suitable for use) in Australian hospital emergency departments or similar settings. Two independent raters evaluated the content and style of each publication against established standards. The readability of the publication, the diagnostic term(s) contained in it and a modified Patient Literature Usefulness Index (mPLUI) were also evaluated. Results: The mean content score was 19.18 ± 8.53 (maximum = 31) and the mean style score was 6.8 ± 1.34 (maximum = 8). The mean Flesch-Kincaid reading ease score was 66.42 ± 4.3. The mean mPLUI score was 65.86 ± 14.97 (maximum = 100). Higher scores on these metrics indicate more desirable properties. Over 80% of the publications used mixed diagnostic terminology. One publication scored optimally on two of the four metrics and highly on the others. Discussion: The content, style, readability and usefulness of written mTBI discharge advice was highly variable. The provision of written information to patients with mTBI is advised, but this variability in materials highlights the need for evaluation before distribution. Areas are identified to guide the improvement of written mTBI discharge advice.

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.

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

Posttraumatic stress symptoms among school personnel after the Jokela school shooting : A longitudial study of exposure, interventions, and symptom changes

Objectives. School personnel who are exposed to school violence are at risk in developing post traumatic stress disorder (PTSD). In Finland there have been two such events in recent years, Jokela school shooting on 7.11.2007 and Kauhajoki school shooting about a year later. The aim of the present study was to examine the presence and change in PTSD symptoms during the first year after the Jokela school shooting. A second aim was to study how the initial exposure and treatment affects the symptom levels of PTSD. There were four hypotheses: 1) The PTSD symptoms are higher for the people who were exposed to the school shooting than for the people who did not face the stressor. 2) The PTSD symptoms increase in the follow up for the people at the school which was not attacked because of the second incident brought up the memories from the Jokela school shooting. 3) Those who have greater exposure to the shooting will have higher level of PTSD symptoms at both 4 and 11 months after the shooting than those who were not directly exposed to the shooting. 4) The PTSD symptoms are reduced more in the group that starts treatment right after the traumatic event than in other groups. Methods. A sample of 24 members of Jokela school personnel were examined four months after the incident and 16 were reassessed 11 month after the incident. To study the change and level of symptoms in other schools during the same period, a group with no exposure to the shooting was used as a control group (n=22). The assessment included Post Traumatic Stress Disorder Checklist Specific (PCL-S) and a social and professional support questionnaire. In addition questions about timing of support and experiences of psychological debriefing were asked. Results and conclusions. Most participants in the study group experienced some symptoms of PTSD at both 4 and 11 months. In both measures three participants from the study group fulfilled the diagnostic criteria for PTSD. The study group and control group differed significantly in overall symptom levels. The study group had more PTSD symptoms in the first measure but in the follow-up the study group’s PTSD symptoms decreased and the control group’s increased. There was a significant change in the study groups PTSD symptom level for those who started treatment right after the traumatic event. The results from this study showed that an exposure to school shooting has long-term effects on school personnel. The findings suggest that it is crucial to plan a comprehensive and long-term treatment for school personnel in the aftermath of school shooting.

A Terapia de Exposição com Realidade Virtual para pacientes com TEPT controlada por um Sistema de Lógica Fuzzy

Nos últimos anos, a área da saúde vem explorando o potencial das novas tecnologias para diagnóstico e tratamentos de muitos distúrbios. Em especial, a tecnologia de Realidade Virtual se destaca por oferecer novas perspectivas de tratamento para diferentes distúrbios neuropsiquiátricos. Por outro lado, a ocorrência de problemas causados por situações traumáticas vem crescendo em todo o mundo. Nesse contexto, o Transtorno de Estresse Pós-Traumático (TEPT) é classificado como um transtorno de ansiedade que se caracteriza por gerar uma classe de comportamentos inadequados a situações que não representam perigo real. Em geral, este transtorno está relacionado à ocorrência de algum evento traumático de grande magnitude no passado. Vários trabalhos foram desenvolvidos utilizando ambientes virtuais tridimensionais (3D) para tratar e diagnosticar este distúrbio. Entretanto, percebe-se uma carência de sistemas que consigam controlar o nível de dificuldade das atividades desenvolvidas nesses ambientes. Nesse caso, esta dissertação tem por objetivo descrever o desenvolvimento e avaliar o potencial de utilização de dois sistemas: um que explora a Realidade Virtual (ARVET) para oferecer cenas virtuais que simulem os estímulos geradores de ansiedade similares aqueles da vida real; e outro que explora a Lógica Fuzzy (SAPTEPT) para classificar os níveis de ansiedade do paciente, possibilitando a análise quali-quantitativa de dados psicofisiológicos e psicométricos. As avaliações realizadas com especialistas na área mostraram que o ARVET pode proporcionar um alto grau de estímulos ansiogênicos e a integração com o SAPTEPT ocorreu de forma satisfatória mostrando o potencial que os sistemas têm de serem utilizados em pacientes reais.

Sociologia do trauma: elementos sociogenéticos e psicogenéticos

O presente trabalho investiga os diferentes processos sociais relacionados ao surgimento do transtorno de estresse pós-traumático (TEPT) no contexto brasileiro. Categoria diagnóstica norte-americana instituída na década de 1980 pela terceira edição do Manual Diagnóstico e Estatístico de Transtornos Mentais (Diagnostic and Statistical Manual of Mental Disorders DSM-III) uma publicação da Associação Americana de Psiquiatria (American Psychiatric Association APA) o TEPT tornou-se, desde a sua aparição, uma das categorias nosológicas mais difundidas, estudadas e diagnosticadas da psiquiatria contemporânea. A partir do cotidiano de um laboratório de pesquisa e tratamento do TEPT, de análises conversacionais dos atendimentos médicos, de um estudo das diferentes escalas psiquiátricas utilizadas no acompanhamento dos pacientes e de pesquisas sobre a mídia relacionada às experiências traumáticas buscou-se entender os entrelaçamentos entre os processos de difusão e a construção da legitimidade da categoria diagnóstica do TEPT. A abordagem aqui proposta pretende ir além do aparente dilema entre uma concepção medicalizada que assumem a existência o TEPT como um fenômeno natural e as abordagens sócio-antropológicas que veem o TEPT como uma experiência culturalmente construída. Por fim, pretendo mostrar, pela investigação dos alicerces políticos e culturais dos denominados transtornos mentais, que o estatuto social dos diagnósticos e dos tratamentos da moderna psiquiatria só pode ser compreendido tendo como referência as dinâmicas de longo prazo nas sociedades contemporâneas.

The Frequency and Impact of Exposure to Potentially Traumatic Events Over the Life Course.

We examined the frequency and impact of exposure to potentially traumatic events among a nonclinical sample of older adults (n = 3,575), a population typically underrepresented in epidemiological research concerning the prevalence of traumatic events. Current PTSD symptom severity and the centrality of events to identity were assessed for events nominated as currently most distressing. Approximately 90% of participants experienced one or more potentially traumatic events. Events that occurred with greater frequency early in the life course were associated with more severe PTSD symptoms compared to events that occurred with greater frequency during later decades. Early life traumas, however, were not more central to identity. Results underscore the differential impact of traumatic events experienced throughout the life course. We conclude with suggestions for further research concerning mechanisms that promote the persistence of post-traumatic stress related to early life traumas and empirical evaluation of psychotherapeutic treatments for older adults with PTSD.

Splintered memories or vivid landmarks? Qualities and organization of traumatic memories with and without PTSD

One hundred and eighty-one students answered a standardized questionnaire on Post-Traumatic Stress Disorder (PTSD): 25 reported trauma(s) and indicated a pattern of after-effects that matched a PTSD symptom profile, whereas 88 indicated trauma(s) but no PTSD symptom profile. Both groups answered a questionnaire addressing the recollective quality, integration and coherence of the traumatic memory that currently affected them most. Participants with a PTSD symptom profile reported more vivid recollection of emotion and sensory impressions. They reported more observer perspective in the memory (seeing themselves 'from the outside'), but no more fragmentation. They also agreed more with the statement that the trauma had become part of their identity, and perceived more thematic connections between the trauma and current events in their lives. The two groups showed different patterns of correlations which indicated different coping styles. Overall, the findings suggest that traumas form dysfunctional reference points for the organization of other personal memories in people with PTSD symptoms, leading to fluctuations between vivid intrusions and avoidance. Copyright © 2003 John Wiley & Sons, Ltd.

Impact of average household income and damage exposure on post-earthquake distress and functioning: A community study following the February 2011 Christchurch earthquake.

Post-traumatic stress, depression and anxiety symptoms are common outcomes following earthquakes, and may persist for months and years. This study systematically examined the impact of neighbourhood damage exposure and average household income on psychological distress and functioning in 600 residents of Christchurch, New Zealand, 4–6 months after the fatal February, 2011 earthquake. Participants were from highly affected and relatively unaffected suburbs in low, medium and high average household income areas. The assessment battery included the Acute Stress Disorder Scale, the depression module of the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder Scale (GAD-7), along with single item measures of substance use, earthquake damage and impact, and disruptions in daily life and relationship functioning. Controlling for age, gender and social isolation, participants from low income areas were more likely to meet diagnostic cut-offs for depression and anxiety, and have more severe anxiety symptoms. Higher probabilities of acute stress, depression and anxiety diagnoses were evident in affected versus unaffected areas, and those in affected areas had more severe acute stress, depression and anxiety symptoms. An interaction between income and earthquake effect was found for depression, with those from the low and medium income affected suburbs more depressed. Those from low income areas were more likely, post-earthquake, to start psychiatric medication and increase smoking. There was a uniform increase in alcohol use across participants. Those from the low income affected suburb had greater general and relationship disruption post-quake. Average household income and damage exposure made unique contributions to earthquake-related distress and dysfunction.