Role of GABAergic signaling and the GABAA receptor subunit gene cluster at 15q11-q13 in autism spectrum disorders, schizophrenia, and heroin addiction

Chia-Chun Huang^{a, b}, Chia-Hsiang Chen^{a, c, d}

^a Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
^b Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
^c Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
^d Department of Psychiatry, Chang Gung Memorial Hospital- Linkou Medical Center, Chang Gung University College of Medicine, Taoyuan, Taiwan

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Abstract
Autism spectrum disorders, schizophrenia, and heroin addiction are all complex disorders with both genetic and environmental components to their etiology. The most common chromosomal abnormality in autism is a maternally derived duplication at 15q11-q13, which is where a cluster of gamma-aminobutyric acid (GABAA) receptor subunit genes lies. In addition, copy number variations in this area have been implicated in the pathogenesis of schizophrenia. These findings suggest that GABAergic signaling might play a crucial role in contributing to susceptibility to the development of autism and schizophrenia. Furthermore, there is considerable evidence supporting a role for GABA neurotransmission in mediating the addictive properties of heroin. Hence, this review explores recent findings related to the involvement of GABAergic system in autism, schizophrenia, and heroin addiction. We also outline the implications that the presence of genetic variants in the GABAA receptor subunit cluster at 15q11-q13 may have on the risk of developing these psychiatric disorders. Finally, we make recommendations for future work that might help define the mechanisms underpinning the neuropathology that contributes to these psychiatric disorders.

Keywords
15q11-q13; Autism; GABAergic; Heroin addiction; Schizophrenia