Our postmortem study showed a reduced expression of phosphorylated CREB in the orbitofrontal cortex of patients with depression.16 This correlation between an altered cAMP-CREB-BDNF cascade and depressive symptoms suggests that in the brains of alcoholics, dysfunction and loss of neurons may be the outcome of altered intracellular signals due to the suppressed CREB activity and the decreased BDNF level. This evidence concerns the gene CREB1 and major depressive disorder.