Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, C18
Stress and inflammation reduce BDNF expression in first-episode psychosis: a pathway to smaller hippocampal volume
V. Mondelli1, A. Cattaneo1, M. Belvederi Murri1, M. Di Forti2, R. Handley2, N. Hepgul1, A. Miorelli2, S. Navari1, A. Papadopoulos1, K. J. Aitchison2, C. Morgan2, R. M. Murray2, P. Dazzan1, C. M. Pariante1
1. Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, United Kingdom. 2. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom.
Background: Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this study was to investigate potential causes and consequences of reduced BDNF expression in these patients, by examining the association between BDNF levels and measures of stress, inflammation and hippocampal volume in first-episode psychosis. Methods: BDNF, interleukin (IL)-6, and tumour-necrosis-factor (TNF) alpha mRNA levels were measured in leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls (recruited between January 2006 and December 2008). In the same subjects, we measured salivary cortisol levels, and collected information about psychosocial stressors (number of childhood trauma, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured, using brain MRI, in a subsample of 19 patients. Results: Patients had reduced BDNF (effect size d=1.3, p<0.001) and increased IL-6 (effect size d=1.1, p<0.001) and TNF-alpha (effect size d=1.7, p<0.001) gene expression levels, when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R square=0.23, p=0.009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels, all significantly and independently predicted a smaller left hippocampal volume (adjusted R square=0.71, p<0.001). Conclusions: Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis, through an effect on BDNF.
Where applicable, experiments conform with Society ethical requirements