Structural Alterations of Synapses in Psychiatric and Neurodegenerative Disorders

Psychiatric and neurodegenerative disorders, such as autism spectrum disorders (ASDs), schizophrenia (SZ), and Alzheimer's disease (AD), pose an immense burden to society. While significant progress has been made in recent years toward understanding the genetic architecture, cellular substrates, brain circuits, and endophenotypes of these disorders, we are still far from being able to treat and prevent these disorders effectively. Genetic, functional imaging, postmortem neuropathological, and pharmacological evidence implicate spiny synapses as key substrates of pathogenesis in ASD, SZ, and AD. Although alterations in dendritic spines, the sites of glutamatergic communication between neurons in the brain, are certainly not the only abnormalities in the brain that are relevant for these diseases, understanding the molecular underpinnings of dendritic spine pathology may provide essential insight into the pathogenesis of these disorders, and can reveal novel drug targets to treat them. In this chapter, we will discuss recent neuropathological, genetic, animal model, and molecular studies that implicate structural alterations at spiny synapses in the pathogenesis of major psychiatric and neurodegenerative disorders, including ASD, SZ, and AD.