Authors: Benedetti, Francesco; Smeraldi, Enrico

Source: Current Pharmaceutical Design, Volume 15, Number 22, August 2009 , pp. 2637-2649(13)

Publisher: Bentham Science Publishers

Abstract:

Despite confirmed evidences about some neurochemical effects of antidepressant treatments, there is still a high level of uncertainty about which biological changes are needed to recover from a major depressive episode. Changes of monoaminergic neurotransmission are paralleled by profound changes in brain metabolism, neural responses to stimuli, sleep architecture, biological rhythms, and, at the intracellular level, neuronal signaling pathways regulating gene expression, neuroplasticity, and neurotrophic mechanisms.

Sleep deprivation targets the biological mechanisms which are responsible for the possibility, unique to mood disorders, of rapid switching between depression, euthymia, and mania. The rapidity of action of sleep deprivation enables the study of the correlates of antidepressant response at close time points, providing a good model to study the biological basis of the antidepressant response and of the patophysiology of affective illness.

Current knowledge suggests that multiple neurobiological effects of sleep deprivation are responsible for the clinical mood amelioration, suggesting a multi-target mechanism of action. An impressive group of brain imaging studies using different brain imaging techniques (positron emission tomography, single photon emission tomography, functional magnetic resonance imaging, proton spectroscopy, arterial spin labeling) showed that clinical response is associated with changes in the functioning of specific brain areas. The combination of these new methodological acquisitions with the classical neurobiological and pharmacogenetic perspective provides an evolving knowledge about brain changes associated with antidepressant response, and will then help to identify the real targets of antidepressant treatment.

Keywords: Sleep deprivation; Antidepressant; Serotonin; Dopamine; Norepinephrine; Glutamate; Synaptic homeostasis; GSK-3

Document Type: Research article

Affiliations: 1: Istituto Scientifico Universitario Ospedale San Raffaele, Dipartimento di Neuroscienze Cliniche, San Raffaele Turro, Via Stamira d'Ancona 20, 20127 Milano, Italy.

Publication date: 2009-08-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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