Antidepressants and pCREB in Hippocampal Neurogenesis and Major Depressive Disorder

Major depressive disorder (MDD) is a mental illness that affects every aspect of the life of a person afflicted with it. There are currently no effective ways to diagnose the disorder through laboratory tests, but investigations into the physiological manifestations of the disease are underway. One such physiological symptom of the disease is neuronal death in the hippocampus, an area of the brain focused on spatial navigation and memory. Phosphorylated cAMP response-binding element protein (pCREB) is a transcription factor that promotes brain-derived neurotrophic factor (BDNF), which induces neurogenesis, especially in the hippocampus. As a result, mice with decreased levels of pCREB or any other promoter of BDNF have decreased spatial navigation skills and decreased memory retention and exhibit symptoms of MDD due to the neuronal death in the hippocampus. We hypothesized that pCREB levels would be highest in human subjects who had been treated with antidepressants and lowest in subjects who were afflicted with MDD but never underwent treatment, with control subjects falling in the middle. To test this, we performed immunohistochemistry using pCREB antibodies on autopsied human hippocampal samples, counterstained them, and the lab will soon perform stereology to measure how much pCREB is present in each sample. If our hypothesis is proven correct it will be the first experiment to show a direct link between pCREB and MDD in humans, which is information that can be used to develop future treatments of MDD.