Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Plexin B3 is genetically associated with verbal performance and white matter volume in human brain

Molecular Psychiatry volume 12, pages 190–194 (2007)Cite this article

Abstract

The presence of genetic influences on cognitive performance and brain volume is well established. However, specific genetic determinants of the variance of these quantitative traits are not yet known. Plexins act as receptors for semaphorins and are implicated in axon guidance, which is a key process in brain development. We have previously shown that plexin B3 is a highly potent stimulator of neurite outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits related to human brain development and cerebral connectivity. We identified several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D and V1596E) conserved at the corresponding positions of the orthologs in mouse and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male patients with schizophrenia. Cognitive performance was measured with the vocabulary test (Wortschatztest (WST)), a method to estimate roughly general intelligence (g). Brain morphology was characterized by magnetic resonance imaging. Compared to subjects not carrying the modern, human-specific haplotype A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis (P=0.0004). This effect could be observed in three independent groups (healthy males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037). Additionally, the haplotype A was associated with increased volume of brain white matter that in turn correlated with performance in the vocabulary test. These findings suggest that plexin B3 may influence cognitive performance, and the development of white matter in vivo in a way similar to its known stimulating effect on neurite outgrowth in vitro. These novel observations warrant further replication in independent samples.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Plomin R, Petrill S . Genetics and intelligence: what's new? Intelligence 1997; 24: 53–77.

    Article  Google Scholar 

  2. Bouchard TJ . Genetic and environmental influences on adult intelligence and special mental abilities. Hum Biol 1998; 70: 257–279.

    PubMed  Google Scholar 

  3. Baare WF, Hulshoff Pol HE, Boomsma DI, Posthuma D, de Geus EJ, Schnack HG et al. Quantitative genetic modeling of variation in human brain morphology. Cereb Cortex 2001; 11: 816–824.

    Article  CAS  Google Scholar 

  4. Vernon PA, Wickett JC, Banzana PG, Stelmack RM. In: Sternberg RJ (ed). Handbook of Intelligence. University Press: Cambridge, 2000, pp 245–264.

    Book  Google Scholar 

  5. Plomin R, Kosslyn SM . Genes, brain and cognition. Nat Neurosci 2001; 4: 1153–1154.

    Article  CAS  Google Scholar 

  6. Posthuma D, De Geus EJ, Baare WF, Hulshoff Pol HE, Kahn RS, Boomsma DI . The association between brain volume and intelligence is of genetic origin. Nat Neurosci 2002; 5: 83–84.

    Article  CAS  Google Scholar 

  7. Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H et al. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 1999; 99: 71–80.

    Article  CAS  Google Scholar 

  8. Hartwig C, Veske A, Krejcova S, Rosenberger G, Finckh U . Plexin B3 promotes neurite outgrowth, interacts homophilically, and interacts with Rin. BMC Neurosci 2005; 25: 53.

    Article  Google Scholar 

  9. Schmidt KH, Metzler P . Wortschatztest (WST). Beltz Test: Weinheim, Germany, 1992.

    Google Scholar 

  10. Tewes U . HAWIE-R Hamburg-Wechsler Intelligenztest für Erwachsene, Revision. Hogrefe: Goettingen, Germany, 1991.

    Google Scholar 

  11. Satzger W, Fessmann H, Engel RR . Liefern HAWIE-R, WST und MWT-B vergleichbare IQ-Werte? Zeitschrift für Diff und Diag Psy 2002; 23: 159–170.

    Google Scholar 

  12. Meisenzahl EM, Rujescu D, Kirner A, Giegling I, Kathmann N, Leinsinger G et al. Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia. Am J Psychiatry 2001; 158: 1316–1319.

    Article  CAS  Google Scholar 

  13. Rujescu D, Meisenzahl EM, Giegling I, Kirner A, Leinsinger G, Hegerl U et al. Methionine homozygosity at codon 129 in the prion protein is associated with white matter reduction and enlargement of CSF compartments in healthy volunteers and schizophrenic patients. Neuroimage 2002; 15: 200–206.

    Article  CAS  Google Scholar 

  14. Andreasen NC, Cohen G, Harris G, Cizadlo T, Parkkinen J, Rezai K et al. Image processing for the study of brain structure and function: problems and programs. J Neuropsychiatr Clin Neurosci 1992; 4: 125–133.

    Article  CAS  Google Scholar 

  15. Andreasen NC, Cizadlo T, Harris G, Swayze II V, O'Leary DS, Cohen G et al. Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging. J Neuropsychiatr Clin Neurosci 1993; 5: 121–130.

    Article  CAS  Google Scholar 

  16. Harris G, Andreasen NC, Cizadlo T, Bailey JM, Bockholt HJ, Magnotta VA et al. Improving tissue classification in MRI: a three-dimensional multispectral discriminant analysis method with automated training class selection. J Comput Assist Tomogr 1999; 23: 144–154.

    Article  CAS  Google Scholar 

  17. Magnotta VA, Heckel D, Andreasen NC, Cizadlo T, Corson PW, Ehrhardt JC et al. Measurement of brain structures with artificial neural networks: two- and three-dimensional applications. Radiology 1999; 211: 781–790.

    Article  CAS  Google Scholar 

  18. Michelson P, Hartwig C, Schachner M, Gal A, Veske A, Finckh U . Missense mutations in the extracellular domain of the human neural cell adhesion molecule L1 reduce neurite outgrowth of murine cerebellar neurons. Hum Mutat 2002; 20: 481–482.

    Article  Google Scholar 

Download references

Author information

Author notes

  1. A Veske

    Present address: Institute of Gene Technology, Tallinn Technical University, Tallinn, Estonia

  2. U Finckh

    Present address: Laboratoriumsmedizin Dortmund, Dortmund, Germany

  3. D Rujescu and E M Meisenzahl: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

    D Rujescu, E M Meisenzahl, I Giegling, T Zetzsche & H-J Möller

  2. Institute of Human Genetics, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    S Krejcova, A Veske, A Gal & U Finckh

  3. Department of Radiology, Ludwig-Maximilians-University, Munich, Germany

    M Reiser & C M Born

Authors
  1. D Rujescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E M Meisenzahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Krejcova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I Giegling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Zetzsche
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Reiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C M Born
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H-J Möller
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Veske
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Gal
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. U Finckh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Rujescu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rujescu, D., Meisenzahl, E., Krejcova, S. et al. Plexin B3 is genetically associated with verbal performance and white matter volume in human brain. Mol Psychiatry 12, 190–194 (2007). https://doi.org/10.1038/sj.mp.4001903

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001903

Keywords

This article is cited by

Search

Advanced search

Quick links