[Neuroplasticity and depression]

Abstract

Early hypotheses on the pathophysiology of mood disorders were based on aberrant intrasynaptic concentrations of the neurotransmitters serotonin and norepinephrine. However, recent neuroimaging and post mortem morphometric studies demonstrated selective structural and morphological (macroscopic and microscopic) changes across various limbic and non-limbic circuits in the brains of depressed patients. Recently, these two types of observations seem to converge at the cellular and molecular level. It has been revealed, that stress and antidepressant treatment have an opposite effect on the intracellular signaling, transcription factors and target genes. In some cases, the factors that are influenced by antidepressants (e.g. cAMP-CREB cascade, BDNF) have also been identified as important mediators of learning and memory. An evolving new hypothesis in the pathophysiology and treatment of depression involves adaptation or plasticity of neural systems. Depression could result from an inability to make the appropriate adaptive responses to stress or aversive stimuli. It is possible that antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of neurons and by increasing cell survival and function.