Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-15T07:27:00.928Z Has data issue: false hasContentIssue false
  • English
  • Français

BDNF and S100B in psychotic disorders: evidence for an association with treatment responsiveness

Published online by Cambridge University Press:  22 November 2013

Noortje W.A. van de Kerkhof ,
Durk Fekkes ,
Frank M.M.A. van der Heijden  and
Willem M.A. Verhoeven
Noortje W.A. van de Kerkhof*
Affiliation:
Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands Erasmus Medical Centre, Departments of Psychiatry and Clinical Chemistry, Rotterdam, The Netherlands
Durk Fekkes
Affiliation:
Erasmus Medical Centre, Departments of Psychiatry and Clinical Chemistry, Rotterdam, The Netherlands
Frank M.M.A. van der Heijden
Affiliation:
Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands
Willem M.A. Verhoeven
Affiliation:
Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands Erasmus Medical Centre, Departments of Psychiatry and Clinical Chemistry, Rotterdam, The Netherlands
*
Dr. N.W.A. van de Kerkhof, MD, Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Stationsweg 46, 5803 AC Venray, The Netherlands. Tel: +31478527339; Fax: +31478527111; E-mail: [email protected]/[email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Brain-derived neurotrophic factor (BDNF) and S100B are involved in brain plasticity processes and their serum levels have been demonstrated to be altered in patients with psychoses. This study aimed to identify subgroups of patients with psychotic disorders across diagnostic boundaries that show a specific symptom profile or response to treatment with antipsychotics, by measuring serum levels of BDNF and S100B.

Methods

The study sample consisted of 58 patients with DSM-IV psychotic disorders. Comprehensive Assessment of Symptoms and History (CASH), Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale for severity and improvement (CGI-S/CGI-I) were applied at baseline and after 6 weeks of antipsychotic treatment. At both time points, serum levels of BDNF and S100B were measured and compared with a matched control sample.

Results

Baseline BDNF and S100B levels were significantly lower in patients as compared with controls and did not change significantly during treatment. Dividing the patient sample according to baseline biochemical parameters (low and high 25% and middle 50%), no differences in symptom profiles or outcome were found with respect to BDNF. However, the subgroups with low and high S100B levels had higher PANSS scores than the middle subgroup. In addition, the high subgroup still showed significantly more negative symptoms after treatment, whereas the low subgroup showed more positive symptoms compared with the other subgroups.

Conclusion

Serum levels of BDNF and S100B are lowered in patients with psychotic disorders across diagnostic boundaries. The differences between high and low S100B subgroups suggest a relationship between S100B, symptom dimensions and treatment response, irrespective of diagnostic categories.

Keywords

BDNFpsychosisS100Bsymptomatologytreatment response
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 4 , August 2014 , pp. 223 - 229
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Van Haren, NEM, Cahn, W, Pol, HEH, Kahn, RS. Schizophrenia as a progressive brain disease. Eur Psychiatry 2008a;23:245–254.CrossRefGoogle ScholarPubMed
2. Owen, MJ, O'Donovan, MC, Thapar, A, Craddock, N. Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 2011;198:173–175.Google Scholar
3. Gogtay, N, Giedd, JN, Lusk, L et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 2004;101:8174–8179.Google Scholar
4. Shaw, P, Kabani, NJ, Lerch, JP et al. Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci 2008;28:3586–3594.Google Scholar
5. Arango, C, Moreno, C, Martínez, S et al. Longitudinal brain changes in early-onset psychosis. Schizophr Bull 2008;34:341–353.Google Scholar
6. Van Haren, NEM, Hulshoff Pol, HE, Schnack, HG et al. Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biol Psychiatry 2008b;63:106–113.CrossRefGoogle ScholarPubMed
7. McGlashan, TH, Hoffman, RE. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Arch Gen Psychiatry 2000;57:637–648.Google Scholar
8. Durany, N, Thome, J. Neurotrophic factors and the pathophysiology of schizophrenic psychoses. Eur Psychiatry 2004;19:326–337.Google Scholar
9. Pan, W, Banks, WA, Fasold, MB, Bluth, J, Kastin, AJ. Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 1998;37:1553–1561.Google Scholar
10. Marchi, N, Cavaglia, M, Fazio, V, Bhudia, S, Hallene, K, Janigro, D. Peripheral markers of blood–brain barrier damage. Clin Chim Acta 2004;342:1–12.CrossRefGoogle ScholarPubMed
11. Karege, F, Schwald, M, Cisse, M. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 2002;328:261–264.Google Scholar
12. Pillai, A, Kale, A, Joshi, S et al. Decreased BDNF levels in CSF of drug-naive first-episode psychotic subjects: correlation with plasma BDNF and psychopathology. Int J Neuropsychopharmacol 2010;13:535–539.Google Scholar
13. Rothermundt, M, Falkai, P, Ponath, G et al. Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF. Mol Psychiatry 2004a;9:897–899.CrossRefGoogle ScholarPubMed
14. Steiner, J, Bogerts, B, Schroeter, ML, Bernstein, H. S100B protein in neurodegenerative disorders. Clin Chem LabMed 2011;49:409–424.CrossRefGoogle ScholarPubMed
15. Pirildar, Ş, Gönül, AS, Taneli, F, Akdeniz, F. Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuro-Psychopharmacol Biol Psychiatry 2004;28:709–713.Google Scholar
16. Twiss, JL, Chang, JH, Schanen, NC. Pathophysiological mechanisms for actions of the neurotrophins. Brain Pathol 2006;16:320–332.Google Scholar
17. Green, MJ, Matheson, SL, Shepherd, A, Weickert, CS, Carr, VJ. Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 2011;16:960–972.Google Scholar
18. Buckley, PF, Pillai, A, Howell, KR. Brain-derived neurotrophic factor: findings in schizophrenia. Curr Opin Psychiatry 2011;24:122–127.Google Scholar
19. Chen, DC, 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 2009;207:375–380.Google Scholar
20. Jindal, RD, Pillai, AK, Mahadik, SP, Eklund, K, Montrose, DM, Keshavan, MS. Decreased BDNF in patients with antipsychotic naïve first episode schizophrenia. Schizophr Res 2010;119:47–51.CrossRefGoogle ScholarPubMed
21. Toyooka, K, Asama, K, Watanabe, Y et al. Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res 2002;110:249–257.Google Scholar
22. Pedrini, M, Chendo, I, Grande, I et al. Serum brain-derived neurotrophic factor and clozapine daily dose in patients with schizophrenia: a positive correlation. Neurosci Lett 2011;491:207–210.Google Scholar
23. Schäfer, BW, Heizmann, CW. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci 1996;21:134–140.Google Scholar
24. Donato, R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 2001;33:637–668.CrossRefGoogle ScholarPubMed
25. Lara, DR, Gama, CS, Belmonte-de-Abreu, P et al. Increased serum S100B protein in schizophrenia: a study in medication-free patients. J Psychiatr Res 2001;35:11–14.Google Scholar
26. Rothermundt, M, Ponath, G, Glaser, T, Hetzel, G, Arolt, V. S100B serum levels and long-term improvement of negative symptoms in patients with schizophrenia. Neuropsychopharmacology 2004b;29:1004–1011.Google Scholar
27. Rothermundt, M, Ahn, JN, Jörgens, S. S100B in schizophrenia: an update. Gen Physiol Biophys 2009;28:F76–F81.Google Scholar
28. Ling, S, Tang, Y, Jiang, F et al. Plasma S-100B protein in Chinese patients with schizophrenia: comparison with healthy controls and effect of antipsychotics treatment. J Psychiatr Res 2007;41:36–42.Google Scholar
29. Sarandol, A, Kirli, S, Akkaya, C, Altin, A, Demirci, M, Sarandol, E. Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment. Prog Neuro-Psychopharmacol Biol Psychiatry 2007;31:1164–1169.Google Scholar
30. Pedersen, A, Diedrich, M, Kaestner, F et al. Memory impairment correlates with increased S100B serum concentrations in patients with chronic schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 2008;32:1789–1792.CrossRefGoogle ScholarPubMed
31. Andreasen, NC, Flaum, MC, Arndt, S. The comprehensive assessment of symptoms and history (CASH): an instrument for assessing diagnosis and psychopathology. Arch Gen Psychiatry 1992;49:615–623.Google Scholar
32. Kay, SR, Fiszbein, A, Opfer, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.Google Scholar
33. Guy, W. ECDEU Assessment Manual for Psychopharmacology, Revised. Bethesda: National Institute of Mental Health, 1976.Google Scholar
34. Post, RM. Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications. J Psychiatr Res 2007;41:979–990.Google Scholar
35. Schroeter, ML, Steiner, J. Elevated serum levels of the glial marker protein S100B are not specific for schizophrenia or mood disorders. Mol Psychiatry 2009;14:235–236.Google Scholar
36. González-Pinto, A, Mosquera, F, Palomino, A et al. Increase in brain-derived neurotrophic factor in first episode psychotic patients after treatment with atypical antipsychotics. Int Clin Psychopharmacol 2010;25:241–245.Google Scholar
37. Qi, LY, Xiu, MH, Chen, DC et al. Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics. Neurosci Lett 2009;462:113–117.Google Scholar
38. Nasrallah, H, Tandon, R, Keshavan, M. Beyond the facts in schizophrenia: closing the gaps in diagnosis, pathophysiology, and treatment. Epidemiol Psychiatr Sci 2011;20:317–327.Google Scholar
39. Bromet, EJ, Kotov, R, Fochtmann, LJ et al. Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry 2011;168:1186–1194.Google Scholar
40. Verhoeven, WMA, Tuinier, S, Van der Burgt, I. Top-down or bottom-up: contrasting perspectives on psychiatric diagnoses. Biologics 2008;2:409–417.Google ScholarPubMed
41. Van Os, J, Kapur, S. Schizophrenia. Lancet 2009;374:635–645.Google Scholar
42. Linscott, RJ, Van Os, J. Systematic reviews of categorical versus continuum models in psychosis: evidence for discontinuous subpopulations underlying a psychometric continuum. Implications for DSM-V, DSM-VI, and DSM-VII. Annu Rev Clin Psychol 2010;6:391–419.CrossRefGoogle ScholarPubMed