Title: Development of a biopsychosocial translational research programme in post-traumatic stress disorder.
Funder: Economic and Social Research Council

Abstract: 1) Establish a longitudinal cohort of Colombians exposed to Armed Conflict to investigate the impact on mental health outcomes and corresponding biopsychosocial risk and resilience factors. 2) Establish the prevalence of common mental disorders including PTSD, Depression and Anxiety and monitor change over a period of 12 months. 3) Identify characteristics of individuals and groups such as educational attainment, degree of trauma exposures, levels of social support and connectedness that confer vulnerability to and resilience from mental disorders. 4) Use gene editing to knock-down neuroligin 1 in a zebrafish model and investigate its effect on behavioral responses to stress. 5) Study the role of neuroligin 1 in stress behaviors by studying the zebrafish brain neurogenomic response to stressors after neuroligin 1 knockout. 6) Evaluate the association between the severity of PTSD symptoms and SNPs in genes of interest, mainly those in the neuroligin 1 pathway and the novel candidate genes generated by our zebrafish work in the studied cohort of patients exposed to armed conflict in Colombia.

Lay abstract: Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric disorder that generates social and profesional difficulties for those who suffer from it. This disorder is triggered by exposure to traumatic events throughout life and characterized by symptoms such as intrusive memories and avoidance behaviors. Multiple studies have identified multiple genetic factors that increase a person's risk of developing PTSD after exposure to a traumatic event. However, these studies have identified many genes and research on the precise role of each of these genetic elements in PTSD is scarce. Moreover, we know very little about the precise neurobiological bases of this disorder and how these interact with social and psychological constructs, and thus more research is needed to understand which processes in the brain become altered in PTSD in order to find an efficient treatment. Recently, a protein involved in synaptic transmission (communication between neurons), neuroligin 1 (nlgn1), has been linked to the risk of developing PTSD. This protein has been previously linked to other psychiatric disorders associated with PTSD, such as anxiety and major depressive disorder, and schizophrenia. The role of the nlgn1 protein in the development of PTSD is unknown, but a number of recent studies suggest it plays an important role in PTSD and the modulation of stress behavior in general. The aim of this proposal is to develop a translational research program, integrating laboratory and clinical research to better understand vulnerability and resilience for PTSD. We propose to develop a mental health program for populations exposed to the armed conflict in municipalities of the department of Cesar, Colombia. Here, we will initially combine epidemiological, clinical and biological approaches to perform a complete evaluation of risk factors, symptoms and outcomes of PTSD in people exposed to the Colombian armed conflict. In parallel we will use a zebrafish animal model to manipulate the nlgn1 gene and study how this alteration affects zebrafish response to stress, anxiety and patterns of gene expression in the brain. Finally, we will combine both components of this study by evaluating how much the nlgn1 gene, and other genes along its pathway, vary across the studied PTSD patients in our study cohort in Cesar, Colombia. Our work will greatly contribute to understanding the molecular underpinnings of PTSD, as well as currently lacking data on PTSD risk and resilience factors among Latino populations, while providing access to a mental health program in a population long affected by violence. Findings of this study could be transferred and applied to the improvement of public health policies to improve the psychological wellbeing and quality of life of those exposed to armed conflict in Colombia.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH