Intervention in the context of development: pathways toward new treatments

Neuropsychiatric disorders vary substantially in age of onset but are best understood within the context of neurodevelopment. Here, we review opportunities for intervention at critical points in developmental trajectories. We begin by discussing potential opportunities to prevent neuropsychiatric disorders. Once symptoms begin to emerge, a number of interventions have been studied either before a diagnosis can be made or shortly after diagnosis. Although some of these interventions are helpful, few are based upon an understanding of pathophysiology, and most ameliorate rather than resolve symptoms. As such, in the next portion of the review, we turn our discussion to genetic syndromes that are rare phenocopies of common diagnoses such as autism spectrum disorder or schizophrenia. Cellular or animal models of these syndromes point to specific regulatory or signaling pathways. As examples, findings from the mouse models of Fragile X and Rett syndromes point to potential treatments now being tested in randomized clinical trials. Paralleling oncology, we can hope that our treatments will move from nonspecific, like chemotherapies thrown at a wide range of tumor types, to specific, like the protein kinase inhibitors that target molecularly defined tumors. Some of these targeted treatments later show benefit for a broader, yet specific, array of cancers. We can hope that medications developed within rare neurodevelopmental syndromes will similarly help subgroups of patients with disruptions in overlapping signaling pathways. The insights gleaned from treatment development in rare phenocopy syndromes may also teach us how to test treatments based upon emerging common genetic or environmental risk factors.