The prefrontal–limbic network in depression: A core pathology of synapse regression

Grey matter loss occurs in different components of the prefrontal-limbic network (PLN) implicated in major depressive disorder (MDD). This must be accounted for by specific pathologies of cells and their processes that comprise the grey matter. In order to identify these a quantitative evaluation of the contributions of neurons, glial cells, blood vessels and extracellular space to the grey matter volume is determined. This forms the basis of evaluating the various claims that the core pathology of certain cell types and/or their processes are responsible for the grey matter loss. It is concluded that it is the loss of synapses and concomitantly that of the dendrites on which they normally impinge that accounts quantitatively for the major loss of grey matter in different components of the PLN in depression.