Although primarily manifested as depression, MDD also results in cognitive impairments.131,132 Neuronal plasticity and cognitive function are associated with transcriptional changes regulated by HDAC-mediated epigenetic modification.133 The overexpression of HDAC2 specifically in neurons resulted in a decrease in dendritic spine density, synapse number, synaptic plasticity, and memory formation in mice. The gene discussed is HDAC2; the disease is major depressive disorder.