Neuregulin 1: an intriguing therapeutic target for neurodevelopmental disorders

Neurodevelopmental psychiatric disorders including schizophrenia (Sz) and attention deficit hyperactivity disorder (ADHD) are chronic mental illnesses, which place costly and painful burdens on patients, their families and society. In recent years, the epidermal growth factor (EGF) family member Neuregulin 1 (NRG1) and one of its receptors, ErbB4, have received considerable attention due to their regulation of inhibitory local neural circuit mechanisms important for information processing, attention, and cognitive flexibility. Here we examine an emerging body of work indicating that either decreasing NRG1-ErbB4 signaling in fast-spiking parvalbumin positive (PV+) interneurons or increasing it in vasoactive intestinal peptide positive (VIP+) interneurons could reactivate cortical plasticity, potentially making it a future target for gene therapy in adults with neurodevelopmental disorders. We propose preclinical studies to explore this model in prefrontal cortex (PFC), but also review the many challenges in pursuing cell type and brain-region-specific therapeutic approaches for the NRG1 system.