The invention features methods for promoting neurogenesis including treatment of psychiatric disorders (e.g., depression, bipolar disorder, and post traumatic stress disorder), drug abuse or addiction, neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, frontotemporal dementia, Huntington's disease, and prion disease), and head trauma (e.g., stroke and physical injury) by inhibition of Sprouty (SPRY) and methods for identification of compounds useful promoting neurogenesis (e.g., useful in the treatment of psychiatric disorders, drug abuse or addiction, neurodegenerative diseases, or head trauma).