A Computational Hypothesis on How Serotonin Regulates Catecholamines in the Pathogenesis of Depressive Apathy

Despite increasing literature supports a strong involvement of dopamine, noradrenaline and serotonin dysfunctions in the pathogenesis of most depressive disorders, the (causal) relationship between those monoamines impairments and the resulting disorder features is still not clear. We propose a hypothesis based on a computational model for which some depressive features may be produced by pathologically low levels of serotonin, which in turn causes a downregulation of catecholamine release. The simulations run with the model demonstrate that this process may be critical to the genesis of apathy, which is one of the most frequent and invalidating features of depressive disorders.