Genetic and cognitive windows into circuit mechanisms of psychiatric disease

Accumulating evidence indicates substantial etiological and pathophysiological heterogeneity as well as overlap within and across psychiatric disorders. Moreover, it is uncertain at what level, besides gross behavior, mental illnesses can be differentiated. To advance our understanding of psychiatric disease, we advocate a more systematic approach in characterizing a small number of animal models by utilizing unequivocal rare disease mutations and targeted cognitive assessment to identify convergent disease circuits and mechanisms. Based on available data, we discuss the possibility that the temporal dynamics of synaptic plasticity play a central role in disease pathophysiology and that the extent and manner in which they are altered in specific neural circuits determine the exact clinical phenotype of diverse disorders.