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Decreased levels of serum brain-derived neurotrophic factor in drug-naïve first-episode schizophrenia: relationship to clinical phenotypes

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Abstract

Objective

There is accumulating evidence that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of patients with schizophrenia. Clinical studies show reductions in BDNF in schizophrenic patients treated with first generation antipsychotics or second generation antipsychotics. However, there have been few systematic studies to examine the relationship between BDNF levels and psychopathology in first-episode and drug-naïve patients with schizophrenia.

Materials and methods

Serum BDNF levels were determined using enzyme-linked-immunosorbent assay (ELISA) in the serum of 88 never-medicated first-episode and 90 healthy controls subjects matched for age and gender. The schizophrenia symptomatology and the depressive symptoms were assessed by the positive and negative syndrome scale (PANSS) and the Hamilton rating (HAMD) scale for depression.

Results

The results showed that BDNF levels were significantly lower in first-episode patients with schizophrenia than in healthy control subjects (9.0 ± 4.2 ng/ml vs 12.1 ± 2.2 ng/ml; F = 37.6; df = 1, 176; p < 0.0001). A significant positive correlation between BDNF levels and PANSS positive subscore was observed (r = 0.29; df = 88; p = 0.008). Furthermore, higher BDNF levels were observed in patients with paranoid subtype of schizophrenia. However, no significant correlation between BDNF and HAMD total score was found.

Conclusion

Low BDNF levels at the onset of psychosis suggest that it may contribute to the pathogenesis of schizophrenia and perhaps, could be a candidate biological marker for positive symptoms.

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References

  • Altar CA, Cai N, Bliven T, Juhasz M, Conner JM, Acheson AL, Lindsay RM, Wiegand SJ (1997) Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389:856–860

    Article  CAS  PubMed  Google Scholar 

  • Buckley PF, Evans D (2006) First-episode schizophrenia. A window of opportunity for optimizing care and outcomes. Postgrad Med Spec No: 5–19

  • Buckley PF, Pillai A, Evans D, Stirewalt E, Mahadik S (2007) Brain derived neurotropic factor in first-episode psychosis. Schizophr Res 91:1–5

    Article  PubMed  Google Scholar 

  • Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474–1486

    CAS  PubMed  Google Scholar 

  • Durany N, Thome J (2004) Neurotrophic factors and the pathophysiology of schizophrenic psychoses. Eur Psychiatr 19:326–337

    Article  Google Scholar 

  • Durany N, Michel T, Zöchling R, Boissl KW, Cruz-Sánchez FF, Riederer P, Thome J (2001) Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res 52:79–86

    Article  CAS  PubMed  Google Scholar 

  • Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269

    Article  CAS  PubMed  Google Scholar 

  • Gama CS, Andreazza AC, Kunz M, Berk M, Belmonte-de-Abreu PS, Kapczinski F (2007) Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder. Neurosci Lett 420:45–48

    Article  CAS  PubMed  Google Scholar 

  • Grillo RW, Ottoni GL, Leke R, Souza DO, Portela LV, Lara DR (2007) Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics. J Psychiatr Res 41:31–35

    Article  PubMed  Google Scholar 

  • Huang TL, Lee CT (2006) Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients. J Psychiatr Res 10:664–668

    Article  Google Scholar 

  • Ikeda Y, Yahata N, Ito I, Nagano M, Toyota T, Yoshikawa T, Okubo Y, Suzuki H (2008) Low serum levels of brain-derived neurotrophic factor and epidermal growth factor in patients with chronic schizophrenia. Schizophr Res 101:58–66

    Article  PubMed  Google Scholar 

  • Jockers-Scherübl MC, Danker-Hopfe H, Mahlberg R, Selig F, Rentzsch J, Schürer F, Lang UE, Hellweg R (2004) Brain-derived neurotrophic factor serum concentrations are increased in drug-naive schizophrenic patients with chronic cannabis abuse and multiple substance abuse. Neurosci Lett 371:79–83

    Article  PubMed  Google Scholar 

  • Karege F, Schwald M, Cisse M (2002) Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328:261–264

    Article  CAS  PubMed  Google Scholar 

  • Kay SR, Opler LA, Lindenmayer JP (1989) The Positive and Negative Syndrome Scale (PANSS): rationale and standardization. Br J Psychiatry 155(Suppl. 7):59–65

    Google Scholar 

  • Narita M, Aoki K, Takagi M, Yajima Y, Suzuki T (2003) Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine. Neuroscience 119:767–775

    Article  CAS  PubMed  Google Scholar 

  • Palomino AG Pinto, Aldama A, Gomez C, Mosquera F, Garcia G (2006) Decreased levels of plasma BDNF levels in first-episode schizophrenia and bipolar disorder patients. Schizophr Res 86:321–322

    Article  PubMed  Google Scholar 

  • Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37:1553–1561

    Article  CAS  PubMed  Google Scholar 

  • Pirildar S, Gönül AS, Taneli F, Akdeniz F (2004) Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuropsychopharmacol Biol Psychiatr 28:709–713

    Article  CAS  Google Scholar 

  • Radka SF, Holst PA, Fritsche M, Altar CA (1996) Presence of brain derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay. Brain Res 709:122–301

    Article  CAS  PubMed  Google Scholar 

  • Reis HJ, Nicolato R, Barbosa IG, Teixeira do Prado PH, Romano-Silva MA, Teixeira AL (2008) Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia. Neurosci Lett 439:157–159

    Article  CAS  PubMed  Google Scholar 

  • Rizos EN, Rontos I, Laskos E, Arsenis G, Michalopoulou PG, Vasilopoulos D, Gournellis R, Lykouras L (2008) Investigation of serum BDNF levels in drug-naive patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 32:1308–1311

    Article  CAS  PubMed  Google Scholar 

  • Shimizu E, Hashimoto K, Watanabe H, Komatsu N, Okamura N, Koike K, Shinoda N, Nakazato M, Kumakiri C, Okada S, Iyo M (2003) Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls. Neurosci Lett 351:111–114

    Article  CAS  PubMed  Google Scholar 

  • Shoval G, Weizman A (2005) The possible role of neurotrophins in the pathogenesis and therapy of schizophrenia. Eur Neuropsychopharmacol 15:19–329

    Article  Google Scholar 

  • Smith MA, Makino S, Kvetnansky R, Post RM (1995) Effects of stress on neurotrophic factor expression in the rat brain, Ann. N.Y. Acad Sci 771:234–239

    Article  CAS  Google Scholar 

  • Szeszko PR, Lipsky R, Mentschel C, Robinson D, Gunduz-Bruce H, Sevy S et al (2005) Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry 10:631–636

    Article  CAS  PubMed  Google Scholar 

  • Takahashi M, Shirakawa O, Toyooka K, Kitamura N, Hashimoto T, Maeda K, Koizumi S, Wakabayashi K, Takahashi H, Someya T, Nawa H (2000) Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Mol Psychiatry 5:293–300

    Article  CAS  PubMed  Google Scholar 

  • Tan 5YL, Zhou DF, Cao LY, Zou YZ, Zhang XY (2005) Decreased BDNF in serum of patients with chronic schizophrenia on long-term treatment with antipsychotics. Neurosci Lett 382:27–32

    Article  CAS  PubMed  Google Scholar 

  • Toyooka K, Asama K, Watanabea Y, Muratakeb T, Takahashib M, Someyab T, Nawaa H (2002) Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatr Res 110:249–257

    Article  CAS  Google Scholar 

  • Weickert CS, Hyde TM, Lipska BK, Herman MM, Weinberger DR, Kleinman JE (2003) Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia, Mol. Psychiatry 8:592–610

    CAS  Google Scholar 

  • Zhang XY, Tan YL, Zhou DF, Cao LY, Wu GY, Xu Q, Shen Y, Haile CN, Kosten TA, Kosten TR (2007) Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics. J Psychiatr Res 41:997–1004

    Article  PubMed  Google Scholar 

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Acknowledgment

Supported by grants from the Beijing Municipal Natural Science Foundation (identification 7072035), the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education, and Clinical Center, United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639.

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Authors and Affiliations

  1. Beijing Huilongguan Hospital, Beijing, People’s Republic of China

    Da Chun Chen, Yan Li Li, Ning Wang, Ke Bing Yang & Mei Hong Xiu

  2. College of Life Science, Guangxi Normal University, Guilin, 541004, People’s Republic of China

    Jing Wang & Sheng Chang Yang

  3. College of Chinese Medicinal Material, Jilin Agricultural University, ChangChun, 130118, People’s Republic of China

    Bo Wang & You Lan Zheng

  4. Marine College, Shandong University at Weihai, Shandong Weihai, 264209, People’s Republic of China

    Chong Xi Zhang

  5. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, VA Medical Center, Research Building 110, Room 229, 2002 Holcombe Boulevard, Houston, Texas, 77030, USA

    Thomas R. Kosten

  6. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, VA Medical Center, Research Building 109, Room 130, 2002 Holcombe Boulevard, Houston, Texas, 77030, USA

    Xiang Yang Zhang

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  1. Da Chun Chen
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  2. Jing Wang
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  3. Bo Wang
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  4. Sheng Chang Yang
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  5. Chong Xi Zhang
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  6. You Lan Zheng
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  7. Yan Li Li
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  8. Ning Wang
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  9. Ke Bing Yang
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  10. Mei Hong Xiu
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  11. Thomas R. Kosten
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  12. Xiang Yang Zhang
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Corresponding authors

Correspondence to Thomas R. Kosten or Xiang Yang Zhang.

Additional information

These three authors (Da Chun Chen, Jing Wang, and Bo Wang) contributed equally to the study.

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Chen, D.C., Wang, J., Wang, B. et al. Decreased levels of serum brain-derived neurotrophic factor in drug-naïve first-episode schizophrenia: relationship to clinical phenotypes. Psychopharmacology 207, 375–380 (2009). https://doi.org/10.1007/s00213-009-1665-6

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  • DOI: https://doi.org/10.1007/s00213-009-1665-6

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