Background: This prospective cohort study investigated the serum levels of brain-derived neurotrophic factor (BDNF), which mediates synaptic plasticity crucial for fear memory extinction, in patients severely injured in motor vehicle accidents (MVAs). Method: A nested, case-controlled study was conducted with 103 MVA survivors: 8 medication-naïve patients who met the criteria for full diagnosis of posttraumatic stress disorder (PTSD) at 6 months after MVA, 10 medication-naïve patients with partial PTSD and 85 patients with no PTSD. PTSD was evaluated by the Clinician-Administered PTSD Scale (CAPS). Serum BDNF levels were measured shortly after the MVA (baseline) and at 6-month follow-up. Results: Posttrauma serum BDNF levels differed between the 3 groups after controlling for age and sex (F = 3.41, p = 0.04), with unexpectedly higher serum BDNF levels seen in the full-PTSD group compared with the no-PTSD group. Additional analysis of patients with serum samples taken at baseline and at 6 months revealed the full-PTSD group had significantly higher serum BDNF levels over the 6 months than the no-PTSD group after controlling for age and sex (F = 6.44, p < 0.01). A positive correlation was seen between changes in serum BDNF levels over 6 months and the CAPS score at 6 months (r = 0.26, p = 0.014). Conclusions: The findings of this study, the first to report longitudinal serum BDNF levels in MVA survivors, suggest that elevated serum BDNF levels could be a biomarker of PTSD after a traumatic event.

1.
Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA: Molecular cloning and expression of brain-derived neurotrophic factor. Nature 1989;341:149-152.
2.
Chen LY, Rex CS, Pham DT, Lynch G, Gall CM: BDNF signaling during learning is regionally differentiated within hippocampus. J Neurosci 2010;30:15097-15101.
3.
Bramham CR, Messaoudi E: BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol 2005;76:99-125.
4.
Takei S, Morinobu S, Yamamoto S, Fuchikami M, Matsumoto T, Yamawaki S: Enhanced hippocampal BDNF/TRKB signaling in response to fear conditioning in an animal model of posttraumatic stress disorder. J Psychiatr Res 2011;45:460-468.
5.
Peters J, Dieppa-Perea LM, Melendez LM, Quirk GJ: Induction of fear extinction with hippocampal-infralimbic BDNF. Science 2010;328:1288-1290.
6.
Ressler KJ, Mayberg HS: Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 2007;10:1116-1124.
7.
Hauck S, Gomes F, Silveira Junior Ede M, Almeida E, Possa M, Ceitlin LH: Serum levels of brain-derived neurotrophic factor in acute and posttraumatic stress disorder: a case report study. Rev Bras Psiquiatr 2009;31:48-51.
8.
Hauck S, Kapczinski F, Roesler R, de Moura Silveira E Jr, Magalhaes PV, Kruel LR, Schestatsky SS, Ceitlin LH: Serum brain-derived neurotrophic factor in patients with trauma psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:459-462.
9.
Dell'osso L, Carmassi C, Del Debbio A, Dell'osso MC, Bianchi C, da Pozzo E, Origlia N, Domenici L, Massimetti G, Marazziti D, Piccinni A: Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:899-902.
10.
Berger W, Mendlowicz MV, Marques-Portella C, Kinrys G, Fontenelle LF, Marmar CR, Figueira I: Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:169-180.
11.
Matsuoka Y, Nishi D, Nakajima S, Yonemoto N, Hashimoto K, Noguchi H, Homma M, Otomo Y, Kim Y: The Tachikawa cohort of motor vehicle accident study investigating psychological distress: design, methods and cohort profiles. Soc Psychiatry Psychiatr Epidemiol 2009;44:341.
12.
Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State'. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
13.
Mori E, Mitani Y, Yamadori A: Usefulness of a Japanese version of the Mini-Mental State test in neurological patients (article in Japanese). Shinkeishinrigaku 1985;1:82-90.
14.
Baker SP, O'Neill B: The injury severity score: an update. J Trauma 1976;16:882-885.
15.
Weiss DS, Marmar CR: The impact of event scale revised; in Wilson JP, Keane TM (eds): Assessing Psychological Trauma and PTSD. New York, The Guilford Press, 1997, pp 399-411.
16.
Asukai N, Kato H, Kawamura N, Kim Y, Yamamoto K, Kishimoto J, Miyake Y, Nishizono-Maher A: Reliability and validity of the Japanese-language version of the impact of event scale-revised (IES-R-J): four studies of different traumatic events. J Nerv Ment Dis 2002;190:175-182.
17.
Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361-370.
18.
Kugaya A, Akechi T, Okuyama T, Okamura H, Uchitomi Y: Screening for psychological distress in Japanese cancer patients. Jpn J Clin Oncol 1998;28:333-338.
19.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655.
20.
Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM: The development of a clinician-administered PTSD scale. J Trauma Stress 1995;8:75-90.
21.
Asukai N, Hirohata S, Kato H, Konishi T: Psychometric properties of the Japanese-language version of the Clinician-Administered PTSD scale for DSM-IV (in Japanese). Jpn J Traumatic Stress 2003;1:47-53.
22.
Sen S, Duman R, Sanacora G: Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biological Psychiatry 2008;64:527-532.
23.
Saruta J, Lee T, Shirasu M, Takahashi T, Sato C, Sato S, Tsukinoki K: Chronic stress affects the expression of brain-derived neurotrophic factor in rat salivary glands. Stress 2010;13:53-60.
24.
Berger W, Mehra A, Lenoci M, Metzler TJ, Otte C, Tarasovsky G, Mellon SH, Wolkowitz OM, Marmar CR, Neylan TC: Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:1279-1284.
25.
Matsuoka Y, Nishi D, Yonemoto N, Hamazaki K, Hamazaki T, Hashimoto K: Potential role of brain-derived neurotrophic factor in omega-3 fatty acid supplementation to prevent posttraumatic distress after accidental injury: an open-label pilot study. Psychother Psychosom 2011;80:310-312.
26.
Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M: Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003;54:70-75.
27.
Krishnan V, Han M-H, Graham DL, Berton O, Renthal W, Russo SJ, LaPlant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ: Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 2007;131:391-404.
28.
Eisch AJ, Bolanos CA, de Wit J, Simonak RD, Pudiak CM, Barrot M, Verhaagen J, Nestler EJ: Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry 2003;54:994-1005.
29.
Berton O, McClung CA, DiLeone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ: Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 2006;311:864-868.
30.
Kang H, Welcher AA, Shelton D, Schuman EM: Neurotrophins and time: Different roles for TRKB signaling in hippocampal long-term potentiation. Neuron 1997;19:653-664.
31.
Korte M, Staiger V, Griesbeck O, Thoenen H, Bonhoeffer T: The involvement of brain-derived neurotrophic factor in hippocampal long-term potentiation revealed by gene targeting experiments. J Physiol Paris 1996;90:157-164.
32.
Patterson SL, Abel T, Deuel TA, Martin KC, Rose JC, Kandel ER: Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron 1996;16:1137-1145.
33.
Gil S, Caspi Y, Ben-Ari IZ, Koren D, Klein E: Does memory of a traumatic event increase the risk for posttraumatic stress disorder in patients with traumatic brain injury? A prospective study. Am J Psychiatry 2005;162:963-969.
34.
Duman RS: Depression: a case of neuronal life and death? Biol Psychiatry 2004;56:140-145.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.