Investigating molecular mechanisms underlying stress and antidepressant responsiveness in adolescent depression

Depression is a major cause of disability worldwide and the onset of depression now occurs much younger than in previous generations, with a prevalence of 4-8% in the adolescent population. Although effective in adults, in most studies, many antidepressants such as SSRIs are not more effective than placebo in treating childhood and adolescent depression. Furthermore, most SSRIs show evidence of an increased risk of suicidality and self-harm in children and adolescents, especially at the initial stages of treatment.
Stress is a major precipitating factor in depression. Ongoing work in our laboratory has shown that juvenile animals may respond differently to stressors than adult animals do. The aim of this project is to investigate the biological mechanisms underlying the differential response to stress in adolescent and adult populations. The hypothalamic –pituitary-adrenal axis mediates the body’s primary response to stress but other mechanisms, including the neuropeptide dynorphin-kappa opioid receptor system, play a role. Furthermore, the interaction between stress and neuroinflammation may play a role in the development of adolescent depression.
The approach will be to use in vivo animal studies of behaviour, coupled with assessment of neuroendocrinological measures, as well as the molecular analysis of isolated tissues to identify the processes involved in the differential response to stress and antidepressants in juvenile and adult animals. Training will be provided in in vivo behavioural pharmacology and all techniques. PhD students are actively encouraged to attend scientific meetings and publish their data.
PhD students will join a vibrant group of neuropharmacology researchers working on a variety of projects across the Department. Through journal clubs and other informal activities students support one another with shared experiences and expertise. There are also excellent opportunities for generic skills training e.g. public engagement activities. Currently, students in the laboratory are self-funded (Government of Saudi Arabia) or receive funding from the Medical Research Council and industrial co-funders. At the end of this PhD you will have acquired the skills to plan and undertake independent research and you will be equipped to follow a variety of different postgraduate career paths.