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.

  • Correspondence
  • Published:

Exercise-induced hippocampal neurogenesis: 5-HT3 receptor antagonism by antipsychotics as a potential limiting factor in Schizophrenia

Molecular Psychiatry volume 23, pages 2252–2253 (2018)Cite this article

Subjects

Aerobic exercise is a well-understood stimulus to hippocampal plasticity [1]. Exercise for individuals with Schizophrenia is especially promising as smaller hippocampal volume (HV) is a core feature, and volume increases are associated with improved clinical and cognitive outcomes [2]. One major component of hippocampal plasticity is adult neurogenesis. Evidence has demonstrated significant deficits in hippocampal cell proliferation or neurogenesis in post-mortem brain tissue of patients with Schizophrenia [3], suggesting that restoration of hippocampal neurogenesis (e.g., by exercise) may have therapeutic implications.

Over the past decade, several studies have investigated the effects of exercise on brain structures, including HV, in individuals with Schizophrenia. However, results have not been consistent. Pajonk and colleagues (2010) demonstrated that following 3-month aerobic training, relative HV significantly increased by 12 and 16% in patients and healthy participants, respectively, but not in patients who played table football (−1%) [1]. The study design was replicated with larger samples using the identical protocol; however, significant increases in HV were not observed in patients or healthy participants [4]. This is in line with another study that utilized 6 months of combined aerobic and resistance training [5]. Conflicting results as to the effects of aerobic exercise on HV are also present among individuals in the early stages of illness [6, 7].

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

References

  1. Pajonk FG, Wobrock T, Gruber O, Scherk H, Berner D, Kaizl I, et al. Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry. 2010;67:133–43.

    Article  Google Scholar 

  2. Lappin JM, Morgan C, Chalavi S, Morgan KD, Reinders AA, Fearon P, et al. Bilateral hippocampal increase following first-episode psychosis is associated with good clinical, functional and cognitive outcomes. Psychol Med. 2014;44:1279–91.

    Article  CAS  Google Scholar 

  3. Allen KM, Fung SJ, Weickert CS. Cell proliferation is reduced in the hippocampus in schizophrenia. Aust N Z J Psychiatry. 2016;50:473–80.

    Article  Google Scholar 

  4. Malchow B, Keeser D, Keller K, Hasan A, Rauchmann BS, Kimura H, et al. Effects of endurance training on brain structures in chronic schizophrenia patients and healthy controls. Schizophr Res. 2016;173:182–91.

    Article  Google Scholar 

  5. Scheewe TW, van Haren NE, Sarkisyan G, Schnack HG, Brouwer RM, de Glint M, et al. Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: a randomised controlled trial in patients with schizophrenia and healthy controls. Eur Neuropsychopharmacol. 2013;23:675–85.

    Article  CAS  Google Scholar 

  6. Rosenbaum S, Lagopoulos J, Curtis J, Taylor L, Watkins A, Barry BK, et al. Aerobic exercise intervention in young people with schizophrenia spectrum disorders; improved fitness with no change in hippocampal volume. Psychiatry Res. 2015;232:200–1.

    Article  Google Scholar 

  7. Lin J, Chan SKW, Lee EHM, Chang WC, Tse M, Su WW, et al. Aerobic exercise and yoga improve neurocognitive function in women with early psychosis. NPJ Schizophr. 2015;1:15047.

    Article  Google Scholar 

  8. Kondo M, Nakamura Y, Ishida Y, Shimada S. The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects. Mol Psychiatry. 2015;20:1428–37.

    Article  CAS  Google Scholar 

  9. Rammes G, Eisensamer B, Ferrari U, Shapa M, Gimpl G, Gilling K, et al. Antipsychotic drugs antagonize human serotonin type 3 receptor currents in a noncompetitive manner. Mol Psychiatry. 2004;9:846–58.

    Article  CAS  Google Scholar 

  10. Lummis SC, Thompson AJ, Bencherif M, Lester HA. Varenicline is a potent agonist of the human 5-hydroxytryptamine3 receptor. J Pharmacol Exp Ther. 2011;339:125–31.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada

    David D. Kim & Alasdair M. Barr

  2. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

    William G. Honer & Ric M. Procyshyn

Authors
  1. David D. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alasdair M. Barr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William G. Honer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ric M. Procyshyn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ric M. Procyshyn.

Ethics declarations

Conflict of interest

AMB has received grants from Bristol-Myers Squibb and the Canadian Institutes of Health Research. WGH has received consulting fees from MDH Consulting, In Silico (no honorarium), Novartis, Eli Lilly, Roche, Otsuka, and Lundbeck; and received grants from the Canadian Institutes of Health Research. RMP has received consulting fees from Janssen, Lundbeck, and Otsuka; is on the speaker’s bureau for Janssen, Lundbeck, and Otsuka; and has received grants from the Canadian Institutes of Health Research. DDK declares that he has no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, D.D., Barr, A.M., Honer, W.G. et al. Exercise-induced hippocampal neurogenesis: 5-HT3 receptor antagonism by antipsychotics as a potential limiting factor in Schizophrenia. Mol Psychiatry 23, 2252–2253 (2018). https://doi.org/10.1038/s41380-018-0022-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-018-0022-8

This article is cited by

Search

Advanced search

Quick links