Multiple lines of evidence support the pathogenic role of neuroinﬂammation in psychiatric illness. Cyclic adenosine monophosphate (cAMP) is a critical regulator of microglia homeostasis; as the predominant negative modulator of cyclic AMP signaling within microglia, and phosphodiesterase 4 (PDE4) represents a promising target for modulating immune function. The approach for pharmacological manipulation of cAMP levels using specifc PDE4 inhibitors provokes an ant-iinﬂammatory response. Specifcally, PDE4 inhibitors have recently emerged as a potential therapeutic strategy for neuroinﬂammatory, neurodegenerative, and psychiatric diseases. Mechanistically, PDE4 inhibitors produce an anti-inﬂammatory and neuroprotection effect by increasing the accumulation of cAMP and activating protein kinase A (PKA), the signaling pathway of which is thought to play an important role in the development of psychiatric disorders. This chapter reviews present knowledge of the relationship between neuroinﬂammation and classical psychiatric disorders (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia) and demonstrates the signaling pathways that underlie the use of PDE4 inhibitors in neuroinﬂammation. In addition, among the four subtypes (A-D) of PDE4, it remains unclear which one exerts suppressive effects on neuroinﬂammation. Understanding how PDE4 and neuroinﬂammation interact can reveal pathogenic clues and help target new preventive and symptomatic therapies for psychiatric illness.
Part of the book: Mechanisms of Neuroinflammation