ABSTRACT
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 12.2 The GABA system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
12.2.1 GABA metabolism, release, and recycling. . . . . . . . . . 220 12.2.2 GABA interneurons . . . . . . . . . . . . . . . . . . . . . . . . . . . 222 12.2.3 GABA receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222 12.2.4 GABA in neuropsychiatric disorders . . . . . . . . . . . . . . 223
12.3 Autism spectrum disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 12.3.1 Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 12.3.2 Etiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 12.3.3 ASD and GABA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
12.3.3.1 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 12.3.3.2 Gene expression. . . . . . . . . . . . . . . . . . . . . . . 226 12.3.3.3 In vivo human studies . . . . . . . . . . . . . . . . . . 227
12.4 Fragile X syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 12.4.1 Clinical features and etiology. . . . . . . . . . . . . . . . . . . . 229 12.4.2 GABA and fragile X. . . . . . . . . . . . . . . . . . . . . . . . . . . 230 12.4.3 Human studies of GABA in fragile X syndrome . . . . . 231
12.5 Rett syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 12.6 Fetal anticonvulsant and alcohol syndromes . . . . . . . . . . . . . . 232 12.7 Theoretical and clinical implications . . . . . . . . . . . . . . . . . . . . 234
12.7.1 Minicolumns and feature discrimination . . . . . . . . . . . 234 12.7.2 Gamma-band activity and feature binding. . . . . . . . . . 234 12.7.3 Clinical implications. . . . . . . . . . . . . . . . . . . . . . . . . . . 235
12.8 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 Acknowledgments and conict of interest statement. . . . . . . . . . . . . 236 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Abstract Autism spectrum disorders (ASD) are neurodevelopmental syndromes characterized by repetitive behaviors and restricted interests, impairments in social behavior and relationships, and in language and communication. Some or all of these symptoms are also observed in a number of other developmental disorders, including fragile X Syndrome, Rett syndrome, and fetal anticonvulsant syndrome (FACS). Emerging evidence suggests that ASD and ASD-associated syndromes may be linked to dysfunction in excitatory:inhibitory (E:I) balance and, in particular, to aspects of inhibitory GABAergic signaling in the brain. This chapter reviews the genetics, molecular neurobiology, and systems neuroscience evidence implicating GABA in these conditions. We conclude by discussing how these decits could explain the specic symptoms observed.
