Neuroprogression: the hidden mechanism of depression

For many years, depressive disorder (DD) was considered a transient and natural disease of people’s mood. Its etiology had been attributed mainly to biochemical alterations of the monoamines and their receptors. Nevertheless, its prevalence and considerable impact on the family and social environment of those afflicted by it have placed the disease as a global public health problem. Neuroprogression is the term used to describe the changes in several psychiatric conditions evidenced and observed in the clinical manifestations, biochemical markers, and cerebral structures of the patients with major depressive disorder (MDD), which frequently overlap with neurodegenerative disorders. DD is considered a potentially aggressive state of neuronal deterioration involving apoptosis, reduced neurogenesis, decreased neuronal plasticity, and increased immune response. Clinically, it encompasses a poor response to treatment and an increase in depressive episodes, both of which bring about vulnerability and decline of functions associated with structural changes in the brain. The interest of this work is to review the metabolic processes involved in the morphologic alterations in the limbic system reported in patients with MDD, as well as the neurologic bases of this complex pathology that include environmental stress, genetic vulnerability, alterations in the neurotransmission, and changes in the neuroplasticity, all of which today bring into limelight a mechanism of progressive neuronal damage.