Bipolar disorder and plasticity: A key target for new treatment

There still are huge unmet needs for improved treatments in bipolar disorder (BD). Attempts were made to decipher the neurobiology of BD and develop new therapeutic targets. Lithium is still considered as gold standard for BD, and increasing studies highlight lithium’s various effects on neurotrophic factors, neurotransmitters, and second messenger systems which all contribute to neuroplasticity. Cellular studies suggested that mitochondrial-mediated pathway involving BCL-2 and calcium regulation, phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, and extracellular regulated kinase (ERK)-mitogen-activated protein kinase (ERK/MAPK) pathway might be promising therapeutic targets. Visualization and assessment of diverse changes of neuroplasticity with higher space and time resolution became possible with development of neuroimaging techniques. Theoretically, these detrimental cascades leading to decreased neuroplasticity can be counteracted simultaneously by inhibiting glycogen synthase kinase-3 β (GSK-3β) activity. Thus increased number of studies indicate that GSK-3β, by modulating neuroplasticity of BD brain, could be an important and viable target for treatment of BD.