Skip to main content
SpringerLink
Log in

Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Objective

Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia.

Materials and methods

We recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale.

Results

BDNF levels were significantly lower in patients than controls (p < 0.001). Cognitive scores on the RBANS and nearly all of its five subscales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, BDNF was positively associated with immediate memory in schizophrenia.

Conclusion

Our findings suggest that BDNF may be involved in the pathophysiology of schizophrenia, and its associated cognitive impairment, especially immediate memory.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Bilder RM, Goldman RS, Robinson D, Reiter G, Bell L, Bates JA, Pappadopulos E, Willson DF, Alvir JM, Woerner MG, Geisler S, Kane JM, Lieberman JA (2000) Neuropsychology of first episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry 157(4):549–559

    Article  PubMed  CAS  Google Scholar 

  • Ciammola A, Sassone J, Cannella M, Calza S, Poletti B, Frati L, Squitieri F, Silani V (2007) Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington’s disease patients. Am J Med Genet B Neuropsychiatr Genet 144B(4):574–577

    Article  PubMed  CAS  Google Scholar 

  • Condray R, Yao JK (2011) Cognition, dopamine and bioactive lipids in schizophrenia. Front Biosci 3:298–330

    Article  Google Scholar 

  • da Chen C, Wang J, Wang B, Yang SC, Zhang CX, Zheng YL, Li YL, Wang N, Yang KB, Xiu MH, Kosten TR, Zhang XY (2009) Decreased levels of serum brain-derived neurotrophic factor in drug-naïve first-episode schizophrenia: relationship to clinical phenotypes. Psychopharmacology 207(3):375–380

    Article  CAS  Google Scholar 

  • Dickerson F, Boronow JJ, Stallings C, Origoni AE, Cole SK, Yolken RH (2004) Cognitive functioning in schizophrenia and bipolar disorder: comparison of performance on the Repeatable Battery for the Assessment of Neuropsychological Status. Psychiatry Res 129(1):45–53

    Article  PubMed  Google Scholar 

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

    Article  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  PubMed  CAS  Google Scholar 

  • First MB, Spitzer RL, Gibbon M (1995) Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID I/P, version 2.0). New York State Psychiatric Institute, Biometrics Research Dept, New York

    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  PubMed  CAS  Google Scholar 

  • Green MF, Kern RS, Braff DL, Mintz J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophr Bull 26(1):119–136

    Article  PubMed  CAS  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 

  • Gunstad J, Benitez A, Smith J, Glickman E, Spitznagel MB, Alexander T, Juvancic-Heltzel J, Murray L (2008) Serum brain-derived neurotrophic factor is associated with cognitive function in healthy older adults. J Geriatr Psychiatry Neurol 21(3):166–170

    Article  PubMed  Google Scholar 

  • Guy W (1976) ECDEU Assessment Manual for Psychopharmacology: Publication ADM 76-388. US Department of Health, Education, and Welfare

  • Harvey PD, Green MF, Keefe RS, Velligan DI (2004) Cognitive functioning in schizophrenia: a consensus statement on its role in the definition and evaluation of effective treatments for the illness. J Clin Psychiatry 65(3):361–372

    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 

  • Hughes C, Kumari V, Soni W, Das M, Binneman B, Drozd S, O’Neil S, Mathew V, Sharma T (2003) Longitudinal study of symptoms and cognitive function in chronic schizophrenia. Schizophr Res 59(2–3):137–146

    Article  PubMed  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 

  • 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  PubMed  CAS  Google Scholar 

  • Komulainen P, Pedersen M, Hänninen T, Bruunsgaard H, Lakka TA, Kivipelto M, Hassinen M, Rauramaa TH, Pedersen BK, Rauramaa R (2008) BDNF is a novel marker of cognitive function in ageing women: the DR’s EXTRA Study. Neurobiol Learn Mem 90(4):596–603

    Article  PubMed  CAS  Google Scholar 

  • Lipska BK, Khaing ZZ, Weickert CS, Weinberger DR (2001) BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs. Eur J Neurosci 14(1):135–144

    Article  PubMed  CAS  Google Scholar 

  • Lu B, Gottschalk W (2000) Modulation of hippocampal synaptic transmission and plasticity by neurotrophins. Prog Brain Res 128:231–241

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Christian K, Lu B (2008) BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 89(3):312–323

    Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10(6):434–445

    Article  PubMed  CAS  Google Scholar 

  • Minichiello L, Korte M, Wolfer D, Kühn R, Unsicker K, Cestari V, Rossi-Arnaud C, Lipp HP, Bonhoeffer T, Klein R (1999) Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24(2):401–414

    Article  PubMed  CAS  Google Scholar 

  • Mizuno M, Yamada K, Olariu A, Nawa H, Nabeshima T (2000) Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J Neurosci 20(18):7116–7121

    PubMed  CAS  Google Scholar 

  • Palmer BW, Heaton RK, Paulsen JS, Kuck J, Braff D, Harris MJ, Zisook S, Jeste DV (1997) Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology 11(3):437–446

    Article  PubMed  CAS  Google Scholar 

  • Palmer BW, Dawes SE, Heaton RK (2009) What do we know about neuropsychological aspects of schizophrenia? Neuropsychol Rev 19(3):365–384

    Article  PubMed  Google Scholar 

  • Palomino AG, Pinto AA, 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 

  • Peng S, Wuu J, Mufson EJ, Fahnestock M (2005) Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem 93(6):1412–1421

    Article  PubMed  CAS  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 Psychiatry 28:709–713

    Article  PubMed  CAS  Google Scholar 

  • Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2:24–32

    Article  PubMed  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  PubMed  CAS  Google Scholar 

  • Randolph C, Tierney MC, Mohr E, Chase TN (1998) The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol 20:310–319

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Riley EM, McGovern D, Mockler D, Doku VC, O’Ceallaigh S, Fannon DG, Tennakoon L, Santamaria M, Soni W, Morris RG, Sharma T (2000) Neuropsychological functioning in first episode psychosis—evidence of specific deficits. Schizophr Res 43(1):47–55

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Rizos EN, Papadopoulou A, Laskos E, Michalopoulou PG, Kastania A, Vasilopoulos D, Katsafouros K, Lykouras L (2010) Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics. World J Biol Psychiatry 11:251–255

    Article  PubMed  Google Scholar 

  • Rund BR (1998) A review of longitudinal studies of cognitive functions in schizophrenia patients. Schizophr Bull 24(3):425–435

    Article  PubMed  CAS  Google Scholar 

  • Schooler NR, Kane JM (1982) Research diagnoses for tardive dyskinesia. Arch Gen Psychiatry 39:486–487

    Article  PubMed  CAS  Google Scholar 

  • Sharma T, Antonova L (2003) Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin North Am 26(1):25–40

    Article  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  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  • Tan YL, 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  PubMed  CAS  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. Psychiatry Res 110:249–257

    Article  PubMed  CAS  Google Scholar 

  • Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD (2002) From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem 9(5):224–237

    Article  PubMed  Google Scholar 

  • Vinogradov S, Fisher M, Holland C, Shelly W, Wolkowitz O, Mellon SH (2009) Is serum brain-derived neurotrophic factor a biomarker for cognitive enhancement in schizophrenia? Biol Psychiatry 66(6):549–553

    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

    Article  PubMed  CAS  Google Scholar 

  • Woods SW (2003) Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 64:663–667

    Article  PubMed  CAS  Google Scholar 

  • Xiu MH, Hui L, Dang YF, Hou TD, Zhang CX, Zheng YL, da Chen C, Kosten TR, Zhang XY (2009) Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 33(8):1508–1512

    Article  PubMed  CAS  Google Scholar 

  • Yang YQ, Sun S, Yu YQ, Li WJ, Zhang X, Xiu MH, da Chen C, De Yang F, Liu H, Li C, Kosten TR, Zhang XY (2011) Decreased serum brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia. Neurosci Lett 502(1):37–40

    Article  PubMed  CAS  Google Scholar 

  • Yu H, Zhang Z, Shi Y, Bai F, Xie C, Qian Y, Yuan Y, Deng L (2008) Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han. J Clin Psychiatry 69(7):1104–1111

    Article  PubMed  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 

  • Zhang XY, Zhou DF, Wu GY, Cao LY, Tan YL, Haile CN, Li J, Lu L, Kosten TA, Kosten TR (2008) BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia. Neuropsychopharmacology 33(9):2200–2205

    Article  PubMed  CAS  Google Scholar 

  • Zhang BH, Tan YL, Zhang WF, Wang ZR, Yang GG, Shi C, Zhang XY, Zhou DF (2009) Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as a screening test in Chinese: reliability and validity. Chin Ment Health J 28:865–869

    Google Scholar 

Download references

Acknowledgment

This study was funded by 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 (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639.

Author information

Authors and Affiliations

  1. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA

    Xiang Yang Zhang, Therese A. Kosten & Thomas R. Kosten

  2. Institute of Mental Health, Peking University, Beijing, 100083, People’s Republic of China

    Jun Liang

  3. Beijing HuiLongGuan Hospital, Beijing, 100096, People’s Republic of China

    Da Chun Chen, Mei Hong Xiu & Fu De Yang

  4. VA Medical Center, Research Building 109, Room 130, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Xiang Yang Zhang

  5. VA Medical Center, Research Building 110, Room 229, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Thomas R. Kosten

Authors
  1. Xiang Yang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Da Chun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mei Hong Xiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fu De Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Therese A. Kosten
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas R. Kosten
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiang Yang Zhang or Thomas R. Kosten.

Additional information

Xiang Yang Zhang, Jun Liang, and Da Chun Chen contributed equally to the study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, X.Y., Liang, J., Chen, D.C. et al. Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia. Psychopharmacology 222, 277–284 (2012). https://doi.org/10.1007/s00213-012-2643-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-012-2643-y

Keywords

Search

Navigation