FTO and major depressive disorder: However, in mice with chronic constraint stress (CRS)-induced depression, the expression of FTO was downregulated significantly in the hippocampus, and interaction with calcium-calmodulin-dependent protein kinase II (CaMKII)/cAMP response element binding protein (CREB) resulted in a reduction of dendritic synaptic structures and the expression of the synapse plasticity molecules synaptophysin and postsynaptic density protein 95 (PSD95), which may be associated with cognitive impairment [68].