The effect of exercise on hippocampal volume and neurotrophines in patients with major depression–a randomized clinical trial.
Abstract
Background The hippocampal volume is reduced in patients with major depression. Exercise leads to an increased hippocampal volume in schizophrenia and in healthy old adults. The effect of exercise on hippocampal volume is potentially mediated by brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin like growth factor 1 (IGF-1). The aim of this trial was to assess the effect of an aerobic exercise intervention on hippocampal volume and serum BDNF, VEGF, and IGF-1 in patients with major depression.Methods Patients were randomized to an aerobic exercise intervention (n=41) or a control condition (n=38). Both interventions consisted of three supervised sessions per week during a three months period.Results Post-intervention the increase in maximal oxygen uptake was 3.90 ml/kg/min (SD 5.1) in the aerobic exercise group and 0.95 ml/kg/min (SD 6.2) in the control group (p=0.03). The hippocampal volume, BDNF, VEGF, or IGF-1 did not differ between the two groups. Post-hoc we found a positive association between change in hippocampal volume and verbal memory (Rho=0.27; p=0.05) and change in hippocampal volume and depressive symptoms (Rho=0.30; p=0.03).Limitations Participation was low in both groups corresponding to an average participation of one session per week.Conclusion Despite a significant increase in maximal oxygen uptake, a pragmatic exercise intervention did not increase hippocampal volume or resting levels of neurotrophines in out-patients with mild to moderate major depression. Trial identifier: ClinicalTrials.gov (NCT00695552).
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Some randomized controlled trials have found that aerobic exercise did not have an impact on hippocampal volume.
“While some RCTs have found that AE did not have an impact on hippocampal volume (Ruscheweyh et al., 2011; Scheewe et al., 2013; Krogh et al., 2014; Rosenbaum et al., 2015; Malchow et al., 2016), it is possible that such discrepancies are caused by a lack of consistency in AE protocols used (Prakash et al., 2015) or in the methods of calculating hippocampal volume (Niemann et al., 2014).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Krogh et al., 2014
One human study found no association between an AE intervention and hippocampal volume or neurotrophin circulation in MDD, but participant attendance was very low and participants showed no reduction in depressive symptoms.
“Just one human study has sought to assess macro-scale structural changes and found no association between an AE intervention and hippocampal volume or neurotrophin circulation (Krogh et al., 2014). However, participant attendance rate to AE sessions was very low in this study, at less than half (one session per week) the attendance rate recorded by studies in other psychiatric populations who did”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Krogh et al., 2014
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References 28 · Cited by 123
- Authors
- Krogh, J., Rostrup, E., Thomsen, C., Elfving, B., Videbech, P., & Nordentoft, M.
- Affiliations
- University of Copenhagen (DK)
- Glostrup Hospital (DK)
- Aarhus University (DK)
- Aarhus University Hospital (DK)
- Corresponding author
- Krogh, Jesper
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 165
- Pages
- 24-30
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2169874459
- Cited by
- 123
- References
- 28
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 14 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 9 · 2015: 7 · 2014: 2
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Lundbeckfonden (R155-2014-1724)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- physical activity, major depressive disorder, hippocampal volume, neurotrophins, brain-derived neurotrophic factor, vascular endothelial growth factor, insulin-like growth factor I, aerobic exercise, VO2max, verbal memory, depressive symptoms
- MeSH terms
- Adolescent, Adult, Major Depressive Disorder, Female, Hippocampus, Humans, Insulin-Like Growth Factor I, Male, Memory, Middle Aged, Exercise, Brain-Derived Neurotrophic Factor, Vascular Endothelial Growth Factor A, Young Adult
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