GRIN2B gene and associated brain cortical white matter changes in bipolar disorder: a preliminary combined platform investigation.
Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (P = 0.001), right frontal region (P = 0.002), left parietal region (P = 0.001), left occipital region (P = 0.001), right occipital region (P < 0.001), and left cingulate gyrus (P = 0.001). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD.
Research Division, Institute of Mental Health, 10 Buangkok View, Singapore 539747.
Carissa Nadia
CN
Kuswanto
Research Division, Institute of Mental Health, 10 Buangkok View, Singapore 539747.
Min Yi
MY
Sum
NUS High School of Mathematics and Science, 10 Clementi Avenue 1, Singapore 129957.
Christopher Ren Zhi
CR
Thng
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228.
Yi Bin
YB
Zhang
Biomedical Imaging Laboratory, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, 11 Biopolis Way, Singapore 138667.
Guo Liang
GL
Yang
Biomedical Imaging Laboratory, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, 11 Biopolis Way, Singapore 138667.
Wieslaw Lucjan
WL
Nowinski
Department of Neuroradiology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433.
Yih Yian
YY
Sitoh
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228 ; Department of Anesthesia, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228.
Chian Ming
CM
Low
Research Division, Institute of Mental Health, 10 Buangkok View, Singapore 539747 ; Department of General Psychiatry, Institute of Mental Health/Woodbridge Hospital, 10 Buangkok View, Singapore 539747.
Kang
K
Sim
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000235:genetics
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid