“Neuroplasticity” subsumes diverse processes of vital importance by which the brain perceives, adapts to, and responds to a variety of internal and external stimuli. The manifestations of neuroplasticity in the adult, central nervous system (CNS) have been characterized #Idarubicin price randurls[1|1|,|CHEM1|]# as including alterations of dendritic function, synaptic remodeling, long-term potentiation (ITT), axonal Inhibitors,research,lifescience,medical sprouting, neurite extension, synaptogenesis, and even neurogenesis (see Mesulam, 1999, for an excellent overview5). Although the potential relevance of neuroplastic events to the pathophysiology

of psychiatric disorders has been articulated for some time,6

recent, morphometric studies of the brain (both in Inhibitors,research,lifescience,medical vivo and postmortem) are beginning to lead to a fuller appreciation of the magnitude and nature of the neuroplastic events involved in the pathophysiology of mood disorders.7-9 In this perspectives paper, we review these data, and discuss their implications not only for changing existing conceptualizations regarding the pathophysiology of MDD, but. also for the strategic development, of improved therapeutic agents. Evidence for impairments of structural plasticity Inhibitors,research,lifescience,medical and cellular resilience in mood disorders Positron emission tomography (PET) imaging studies

have revealed multiple abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in limbic and prefrontal cortex (P.FC) structures in mood disorders. Inhibitors,research,lifescience,medical These abnormalities implicate limbic-thalamic-cortical and limbic-cortical-striatal-pallidal-thalamic circuits, involving the amygdala, orbital, and medial PFC, and anatomically related parts of the striatum and thalamus in the pathophysiology of mood disorders. Interestingly, recent morphometric magnetic resonance imaging (MRI) and postmortem investigations Inhibitors,research,lifescience,medical have also demonstrated abnormalities of brain structure that, persist independently of mood state and may contribute to the corresponding abnormalities of metabolic activity (discussed in references 2 and 10). Thus, structural imaging studies Thiamine-diphosphate kinase have demonstrated reduced gray matter volumes in areas of the orbital and medial PFC, ventral striatum, and hippocampus, and enlargement of the third ventricle in mood-disordered samples relative to healthy control samples (Table I).11-77 Complementary postmortem neuropathological studies have shown abnormal reductions in cortex volume, glial cell counts, and/or neuron size in the subgenual PFC, orbital cortex, dorsal anterolateral PFC, and amygdala (Table II).