Genetic association studies of glutamate, GABA and related genes in schizophrenia and bipolar disorder: a decade of advance.
Schizophrenia (SZ) and bipolar disorder (BD) are debilitating neurobehavioural disorders likely influenced by genetic and non-genetic factors and which can be seen as complex disorders of synaptic neurotransmission. The glutamatergic and GABAergic neurotransmission systems have been implicated in both diseases and we have reviewed extensive literature over a decade for evidence to support the association of glutamate and GABA genes in SZ and BD. Candidate-gene based population and family association studies have implicated some ionotrophic glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further replication studies are needed to validate these results. There is at present no consensus on specific single nucleotide polymorphisms or haplotypes associated with the particular candidate gene loci in these illnesses. The genetic architecture of glutamate systems in bipolar disorder need to be better studied in view of recent data suggesting an overlap in the genetic aetiology of SZ and BD. There is a pressing need to integrate research platforms in genomics, epistatic models, proteomics, metabolomics, neuroimaging technology and translational studies in order to allow a more integrated understanding of glutamate and GABAergic signalling processes and aberrations in SZ and BD as well as their relationships with clinical presentations and treatment progress over time.
Cherlyn
Suat Ying Tan
SY
Institute of Mental Health/Woodbridge Hospital, 10 Buangkok View, Singapore 539747, Singapore.
Woon
Puay San
PS
Liu
Jian Jun
JJ
Ong
Wei Yi
WY
Tsai
Guo Chuan
GC
Sim
Kang
K
D000818:Animals; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology; D056726:Genetic Association Studies; D018698:Glutamic Acid / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000235:genetics* / Q000378:metabolism
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid