Anxiety and depression: A matter of stiffness?

Cells react to stress by the universal responses of "fluidization" or "reinforcement" (stiffening) of the cytoplasm, through dramatic re-arrangements of the cytoskeleton. Here it is suggested that, at a supracellular level, the brain exhibits such a fundamental behavior as part of its complex response to stress: it is hypothesized that the soft gel formed by brain cell cytoskeletons and the surrounding extracellular matrix (the "cytoskeletons-matrix system") undergoes transitions either to sol (fluidization) or stiff gel (reinforcement) as a very fundamental and evolutionarily conserved brain response to stress, alongside more sophisticated neural pathways. Sol state corresponds to increased cell activity (a sort of "fight or flight" response), whereas stiff gel state corresponds to inactivity (an "immobility" strategy). Psychological stress, through simple stress signals such as pH changes, would lead to an initial tissue fluidization in key regions of the brain, followed, if the stress stimuli persist, by reinforcement (slow formation of actomyosin stress fibers and matrix stiffening). It is also hypothesized that the cytoskeletons-matrix system is one of the biological correlates of so-called "background feelings", i.e conscious feelings built on inner chemical-physical states of the body. Optimal dynamics of the cytoskeletons-matrix system would contribute to a core feeling of well-being, while shifts towards fluidization (activation) or stiffening (inactivation) would contribute to background feelings at the basis of anxiety and stress-induced depression, respectively. It is suggested that the cytoskeletons-matrix system behaves as a "self-organized critical system", anxiety and depression arising whenever the system is driven too far from the optimal critical point. Finally, some application hints from the proposed ideas are given.