Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder Liliana Dell'Osso a , Claudia Carmassi a, ⁎, Alessandro Del Debbio a , Mario Catena Dell'Osso a , Carolina Bianchi a , Eleonora da Pozzo a , Nicola Origlia b , Luciano Domenici b,c , Gabriele Massimetti a , Donatella Marazziti a , Armando Piccinni a a Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Via Roma 67, 56100 Pisa, Italy b Institute of Neuroscience, National Research Council, Pisa, Via Moruzzi 1, Pisa, Italy c Dipartimento di Scienze e Tecnologie Biomediche, University of L'Aquila, Loc. Coppito, L'Aquila, Italy abstract article info Article history: Received 25 February 2009 Received in revised form 1 April 2009 Accepted 20 April 2009 Available online 3 May 2009 Keywords: Brain-Derived Neurotrophic Factor (BDNF) BDNF plasma levels Neurotrophins Post-traumatic stress disorder Stress Trauma In both animals and humans, stress has been demonstrated to reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which promotes the proliferation, survival and differentiation of neurons. Although traumatic events have been found to be associated with lower BDNF plasma levels in affective disorders, no study has explored this parameter in patients with post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were assessed by the Structured Clinical Interview for DSM-IV, while the specific symptoms were examined in the patients by means of the Impact of Event Scale for PTSD and the traumas experienced were assessed by using the Life Events Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa method. The results, while showing significantly lower BDNF levels in PTSD patients, as compared with those of healthy subjects (p = 0.001), although obtained in a small sample size, would suggest that this NT may be involved in the pathophysiology of PTSD. © 2009 Elsevier Inc. All rights reserved. 1. Introduction Post-traumatic stress disorder (PTSD) is a complex syndrome re- sulting from the exposure to a severe traumatic event that poses effective or threatened death or injury and produces intense fear, helplessness or horror (American Psychiatric Association, APA, 2000; Keane et al., 2006). Clinically, PTSD patients show a wide range of symptoms including re-experiencing (nightmares, intrusive thoughts and flashbacks of the trauma), avoidance (amnesia for the trauma) and hyperarousal (exaggerated startle response, sleep disturbances and impaired learning and concentration). Different brain areas have been supposed to be involved in the pathophysiology of PTSD, in particular the hippocampus, amygdala and cingulate belonging to the limbic system, together with the medial and dorsolateral prefrontal cortex (Bremner, 2003). Different studies have also focused upon the modulation of the stress response and, as such, on the role of the hypothalamic-pituitary-adrenal (HPA) axis and the catecholamine/ sympathetic nervous system, so that PTSD has been also depicted as a condition characterized by normal to low cortisol levels, despite hypersecretion of corticotrophin releasing factor (Newport and Nemeroff, 2000). Neuroimaging studies in patients with PTSD triggered by combat exposure or early childhood physical/sexual abuse, showed a reduced hippocampal size, when compared with healthy individuals or sub- jects with other types of traumas (Bremner et al., 1995, 1997, 2003; Stein et al., 1997; Villarreal et al., 2002). These structural abnormalities are consistent with the deficits in learning and memory of PTSD patients and provide support for the hypothesis that stress may be associated with hippocampal damage or dysfunction (Bremner et al., 2003). In addition, preclinical studies have suggested that prolonged stress, that leads to atrophy and cell loss in limbic structures (Czéh and Lucassen, 2007), may decrease the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) known to promote neuronal survival and regulate the proliferation and differentiation of nerve cells in both the peripheral and central nervous system (Hartmann et al., 2001). In animal models the exposure to footshock or maternal separation reduces hippocampal BDNF expression through a down-regulation of its mRNA levels (Duman, 2002; Rasmusson et al., Progress in Neuro-Psychopharmacology & Biological Psychiatry 33 (2009) 899–902 Abbreviations: APA, American Psychiatric Association; BDNF, Brain-Derived Neuro- trophic Factor; CAPS, Clinician Administered PTSD Scale; DSM, Diagnostic and Statistical Manual of mental disorders; DSM-TR, Diagnostic and Statistical Manual of Mental Disorders-Text Revision; EDTA, Ethylenediaminetetraacetic acid; ELISA, Enzyme-Linked Immunosorbent Assay; ANOVA, Analysis of Variance; HPA, Hypothalamic-Pituitary- Adrenal; IES, Impact of Event Scale; IgG, immunoglobuline G; LEC, Life Events Checklist; HCl, Hydrochloric Acid; mRNA, Messanger-Ribonucleic Acid; NT, Neurotrophin; PD, Panic Disorder; PTSD, Post-Traumatic Stress Disorder; SCID-I/P, Structured Clinical Interview for DSM-IV Axis-I Disorders Patient Version; SPSS, Statistical Package for Social Science; TrkB, tyrosine kinase-activating receptor. ⁎ Corresponding author. Tel.: +39050835412; fax: +39 05021581. E-mail address: ccarmassi@gmail.com (C. Carmassi). 0278-5846/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2009.04.018 Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp