Genetic risk for white matter abnormalities in bipolar disorder.
White matter deficits have been demonstrated in people with bipolar disorder, schizophrenia and their unaffected relatives. These deficits are supported by evidence from post-mortem studies, including microarray investigations which have repeatedly implicated abnormal myelin-associated gene expression. Furthermore, several risk-associated genes have now been identified that encode for proteins which have effects on white matter integrity. These genes include neuregulin-1 (NRG1) polymorphisms of which have been associated with risk to bipolar disorder. NRG1 has been shown to have effects on axonal migration, myelination and oligodendrocyte function. We and others have also shown that 5' risk-associated genetic variants in NRG1 are associated with reductions in both white matter density and integrity in regions associated with prefrontal connectivity. These findings are discussed in the context of the current literature, along with possible future research directions.
McIntosh
Andrew M
AM
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Hall
Jeremy
J
Lymer
G Katherine S
GK
Sussmann
Jessika E D
JE
Lawrie
Stephen M
SM
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020772:Internal Capsule / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009415:Nerve Net / Q000473:pathology; D020890:Neuregulin-1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000473:pathology
C094131:NRG1 protein, human; D020890:Neuregulin-1