Neuroplasticity: from MRI to depressive symptoms

Morphological and functional changes have been repeatedly reported in the brain organization of depressed patients. The main modifications demonstrated by structural magnetic resonance imaging (MRI) are a reduction in the gray matter volume within the prefrontal cortex, the hippocampus, and the striatum. The reduction in gray matter volume and the morphological atrophy are probably due to an excess of neural loss (apoptosis) and an altered regulation of the neurotrophic processes. Hence, a deficit in neurotrophic factor synthesis (brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, NT-4/5, Bcl-2, etc.) may be responsible for increased apoptosis in the hippocampus and prefrontal cortex corresponding to the cognitive impairment described in depression. This hypothesis seems to be confirmed by the decreased expression of neurotrophic factors (e.g., BDNF mRNA) in animal models of depression. In parallel, the neural plasticity (functional aspects of synaptic connectivity and long-term potential activity [LTP]) is decreased. However, the most interesting data concern the possible reversibility of this dysregulation with antidepressant treatment. For example, communication between the hippocampus and the prefrontal cortex could be re-established, enabling in a way the cognitive processes to be reset. From a clinical point of view, the consequences of such a phenomenon are manifold: - apoptosis and neurotrophic deficits could explain most of the symptoms of depression depending on the regions concerned; - the resulting alterations in neuroplasticity could explain the dysconnectivity found between the same regions; - enhancing neurotrophic synthesis in those regions could not only stimulate synaptogenesis and reverse neural (dendritic) atrophy but could also play a positive role in UP genesis which is crucial for re-establishing adapted communication. (C) 2004 Published by Elsevier B.V.