Association between hippocampal structure and serum Brain-Derived Neurotrophic Factor (BDNF) in healthy adults: A registered report

Neuroimage. 2021 Aug 1;236:118011. doi: 10.1016/j.neuroimage.2021.118011. Epub 2021 Apr 20.


The hippocampus is a highly plastic brain structure supporting functions central to human cognition. Morphological changes in the hippocampus have been implicated in development, aging, as well as in a broad range of neurological and psychiatric disorders. A growing body of research suggests that hippocampal plasticity is closely linked to the actions of brain-derived neurotrophic factor (BDNF). However, evidence on the relationship between hippocampal volume (HCV) and peripheral BDNF levels is scarce and limited to elderly and patient populations. Further, despite evidence that BDNF expression differs throughout the hippocampus and is implicated in adult neurogenesis specifically in the dentate gyrus, no study has so far related peripheral BDNF levels to the volumes of individual hippocampal subfields. Besides its clinical implications, BDNF-facilitated hippocampal plasticity plays an important role in regulating cognitive and affective processes. In the current registered report, we investigated how serum BDNF (sBDNF) levels relate to volumes of the hippocampal formation and its subfields in a large sample of healthy adults (N = 279, 160 f) with a broad age range (20-55 years, mean 40.5) recruited in the context of the ReSource Project. We related HCV to basal sBDNF and, in a subsample (n = 103, 57 f), to acute stress-reactive change in sBDNF. We further tested the role of age as a moderator of both associations. Contrary to our hypotheses, neither basal sBDNF levels nor stress-reactive sBDNF change were associated with total HCV or volume of the dentate gyrus/cornu ammonis 4 (DG/CA4) subfield. We also found no evidence for a moderating effect of age on any of these associations. Our null results provide a first point of reference on the relationship between sBDNF and HCV in healthy mid-age, in contrast to patient or aging populations. We suggest that sBDNF levels have limited predictive value for morphological differences of the hippocampal structure when notable challenge to its neuronal integrity or to neurotrophic capacity is absent.

Keywords: Brain-Derived Neurotrophic Factor (BDNF); Dentate gyrus; Hippocampal subfields; Hippocampal volume; Neurotrophins; Stress-reactive BDNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain-Derived Neurotrophic Factor / blood*
  • Dentate Gyrus / anatomy & histology
  • Dentate Gyrus / diagnostic imaging
  • Female
  • Hippocampus / anatomy & histology*
  • Hippocampus / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Young Adult


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human