Speaker 1: John O’Brien, UK

Objectives: There is growing evidence that many emotionregulation processes operate at implicit levels, and the ability to regulate emotions without the need for conscious effort is important for mental health. The glucocorticoid hormones (cortisol in humans) are crucial for stress responses and adaptation, and posttraumatic stress disorder (PTSD) has been associated with both cortisol dysregulation and abnormalities in brain regions involved in emotion regulation. However, how cortisol affects implicit emotion regulation in PTSD, until now has not been studied. In the present study, we examined the effects of exogenous synthetic cortisol (hydrocortisone, HCT) administration on emotion regulation neurocircuits in individuals with and without PTSD. Methods: Here, we used administration of HCT, functional magnetic resonance imaging (fMRI) and the shifting emotion appraisal task (SEAT) which probes neurocircuits of two types of implicit emotion regulation i.e., attention shifting and cognitive appraisal to examine the effect of cortisol on emotion regulation neurocircuits. Using counter-balanced, placebo-controlled, double-blind, within-subject design, 11 individuals diagnosed with PTSD and 11 healthy controls were scanned with bloodoxygen-level-dependent sensitive whole-brain fMRI on 3.0 Tesla GE Signa System, while performing the SEAT on two separate occasions, once following 100mg HCT administration and once following Placebo administration. Preprocessing of fMRI data and analyses were conducted in Statistical Parametric Mapping 8 (SPM8; the Wellcome Trust Centre for Neuroimaging). Results: Experimental manipulation robustly activated neurocircuits involved in emotional regulation by attention shifting and cognitive appraisal respectively. Shifting attention to background context resulted in significant activation in the place processing areas such as parahippocampal place area and attention control areas such as dorsolateral PFC. Cognitive appraisal elicited significant activity in the broad area of medial and left lateral PFC. Differential cortisol modulations of task related activation were observed in the hippocampus and subgenual anterior cingulate cortex (sgACC) between in controls and in patients with PTSD. The left hippocampus activation during shifting attention to background context was decreased by HCT administration in patients with PTSD while increased in Controls. Differential activation during cognitive appraisal was significant in the sgACC, and this effect is mainly driven by enhanced activation of this area by HCT administration in patients with PTSD. Conclusions: We used a probe of the implicit emotion regulation processes to assess how cortisol affects the emotion regulation neurocircuits, and demonstrated that elevation of cortisol is associated with reduced activity in the hippocampus during shifting attention to background context and increased activity in the sgACC during cognitive appraisal only in patients with PTSD. These results suggest that the way hormonal activity affects the brain regions involved in emotion regulation is altered in patients with PTSD, possibly reflecting altered sensitivity of the glucocorticoid receptor in these regions in patients with PTSD. S27: CINP –ICGP Panel Molecular Mechanisms of Late Life Mood and Cognitive Disorders: Targets for Prevention and Intervention Chair: Gwenn Smith, USA Co-Chair: Jeong Lan Kim, Republic of Korea Speaker 1: John O’Brien, UK Title: Neuroinflammatory changes in late life depression: the NIMROD study John T O’Brien,1, Li Su1, Yetunde O Faluyi1, Young T Hong2,3, Tim D Fryer2,3, Guy B Williams2,3, Robert Arnold1, Luca Passamonti3, Patricia Vázquez Rodríguez3, Ajenthan Surendranathan1, W Richard Bevan-Jones1, Franklin Aigbirhio2,3, James B Rowe3,4,5 1 Department of Psychiatry, University of Cambridge, UK, 2 Wolfson Brain Imaging Centre, University of Cambridge, UK. 3 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., 4 Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, UK., 5 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.