Figure 7.

Hypothetical mediation models for (A) the association between brain-derived neurotrophic factor (BDNF) signaling, serotonin fibers and neurotransmission, hippocampal volume, and depressive symptoms. Depressive symptoms are modeled here as a latent cluster of symptoms. In this model, BDNF signaling has a reciprocal relationship with serotonin such that reductions in both lead to decreased hippocampal volume. There is a circular path between decreased hippocampal volume, increased depressive symptoms, and decreased serotonin fibers and neurotransmission. Thus, in this model, it appears as if decreased hippocampal volume precedes depressive symptoms, but increased depressive symptoms might have compounding effects on decreased hippocampal volume by magnifying the loss of serotonergic fibers. In model (B), we hypothesize that increased aerobic exercise leads to increased production of BDNF, which in turn leads to increased hippocampal volume (e.g., dendritic branching and cell proliferation) and improved memory function. However, similar to model (A), we predict that exercise influences hippocampal volume through several pathways, BDNF being only one of them. Furthermore, exercise could also improve memory function by influencing several different molecules and brain networks in addition to the hippocampus.