Serotonin and neuroplasticity - Links between molecular, functional and structural pathophysiology in depression.
Serotonin modulates neuroplasticity, especially during early life, and dysfunctions in both systems likewise contribute to pathophysiology of depression. Recent findings demonstrate that serotonin reuptake inhibitors trigger reactivation of juvenile-like neuroplasticity. How these findings translate to clinical antidepressant treatment in major depressive disorder remains unclear. With this review, we link preclinical with clinical work on serotonin and neuroplasticity to bring two pathophysiologic models in clinical depression closer together. Dysfunctional developmental plasticity impacts on later-life cognitive and emotional functions, changes of synaptic serotonin levels and receptor levels are coupled with altered synaptic plasticity and neurogenesis. Structural magnetic resonance imaging in patients reveals disease-state-specific reductions of gray matter, a marker of neuroplasticity, and reversibility upon selective serotonin reuptake inhibitor treatment. Translational evidence from magnetic resonance imaging in animals support that reduced densities and sizes of neurons and reduced hippocampal volumes in depressive patients could be attributable to changes of serotonergic neuroplasticity. Since ketamine, physical exercise or learning enhance neuroplasticity, combinatory paradigms with selective serotonin reuptake inhibitors could enhance clinical treatment of depression.
NEUROIMAGING LABs (NIL) - PET & MRI & EEG & Chemical Lab Department of Psychiatry and Psychotherapy Medical University of Vienna.
Christoph
C
Kraus
Neuroscience Center, University of Helsinki, Helsinki, Finland.
Eero
E
Castrén
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria(1).
Siegfried
S
Kasper
NEUROIMAGING LABs (NIL) - PET & MRI & EEG & Chemical Lab Department of Psychiatry and Psychotherapy Medical University of Vienna. Electronic address: rupert.lanzenberger@meduniwien.ac.at.
Rupert
R
Lanzenberger
D000293:Adolescent; D000818:Animals; D000928:Antidepressive Agents; D003863:Depression; D003865:Major Depressive Disorder; D006801:Humans; D009473:Neuronal Plasticity; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
D000928:Antidepressive Agents; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
Brain-derived neurotrophic factor; Depression; Neurogenesis; Neuroplasticity; Serotonin; Structural magnetic resonance imaging; Voxel-based morphometry