title: Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.
abstract: BACKGROUND
  Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control 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
  Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients.
  
  
  RESULTS
  Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .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(2) = 0.23, P = .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(2) = 0.71, P < .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.
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK.|Genetics Unit, IRCCS San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cattaneo
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK.
authors.forename: Martino Belvederi
authors.initials: MB
authors.lastname: Murri
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Forti
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Rowena
authors.initials: R
authors.lastname: Handley
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK.
authors.forename: Nilay
authors.initials: N
authors.lastname: Hepgul
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Miorelli
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Serena
authors.initials: S
authors.lastname: Navari
authors.affiliation: Affective Disorders Laboratory, National Affective Disorders Unit, Bethlem Royal Hospital, Kent, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Papadopoulos
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.|King's College London, Institute of Psychiatry, MRC SGDP Centre, London, UK.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Morgan
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychosis Studies, London, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
authors.affiliation: King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK.
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D011618:Psychotic Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor