While functional magnetic resonance imaging (fMRI) studies of patients with depression have consistently shown overactivity in the frontolimbic circuitry, including the dorsolateral prefrontal cortex (dPFC) and hippocampus during working memory performance (Harvey, 2005; Walsh, 2007), SSRIs are thought to reduce glutamatergic overactivity in the hippocampus and facilitate dendritic spine formation via brain derived neurotrophic factor (BDNF) (Nibuya, 1996; Dincheva, 2012), calcium/calmodulin dependent kinase II (Elgersma, 2004) or changes in gene expression (du Jardin, 2016). The gene discussed is BDNF; the disease is major depressive disorder.