Cyclic AMP response element-binding protein and depression

Depression is one of the most common and most devastating psychiatric disorders. Although a variety of treatment strategies is available, a major problem in its therapy consists of the unpredictability of the drug response. Furthermore, most antidepressant drugs, which usually increase 5-HT and norepinephrine levels in the synaptic cleft, are likely to produce side effects. Therefore, the quest for new options in antidepressant treatment is urgent. A novel therapeutic approach beyond manipulating the neurotransmitter-receptor interaction consists of targeting signal transduction and gene expression pathways. One of the best investigated pathways is the cyclic AMP second messenger system which ultimately influences gene expression by activating the transcription factor cyclic AMP response element binding protein via phosphorylation. There is evidence that this cAMP-PKA-CREB system is disturbed in depression and that an increased cyclic AMP response element binding protein activity may result in an improved neural plasticity, which in turn could contribute to amelioration of the clinical symptoms of depression.