Effect of genetic variant in BICC1 on functional and structural brain changes in depression.
Genes and early-life adversity (ELA) interactively increase the risk of developing major depressive disorder (MDD). A recent genome-wide association study suggests that the minor T-allele of single-nucleotide polymorphisms in the bicaudal C homolog 1 gene (BICC1) has a protective role against MDD. The aims of the study were to investigate whether the minor T-allele of BICC1 is protective against hippocampal structural brain changes, whether it is associated with increased functional brain activity in the emotion regulation system, and how ELA would modify this association. Forty-four patients with MDD and 44 healthy controls were investigated using structural magnetic resonance imaging (MRI) and functional MRI with an emotion inhibition task. Analysis of a single-nucleotide polymorphism in the BICC1-1 (rs999845) gene was performed. Right hippocampal bodies of patients and controls without a history of ELA and who carry the protective T-allele of BICC1 were significantly larger compared with those participants homozygous for the major C-allele of BICC1. However, MDD patients with ELA, who carry the T-allele, had smaller hippocampal head volumes compared with MDD patients without ELA. FMRI showed that patients and controls carrying the protective T-allele of BICC1 activate the emotion regulation system significantly more compared with those participants homozygous for the major C-allele (p<0.05, family wise error corrected). These results are suggestive that the minor T-allele of BICC1 has a protective role against MDD and its known structural and functional brain changes. However, this protective effect seems to be lost in the case of co-occurrence of ELA.
Integrated Neuroimaging Group, Department of Psychiatry and Institute of Neuroscience, School of Medicine, Trinity College Dublin, University of Dublin, College Green, Dublin, Ireland.
Rachel
R
Bermingham
Angela
A
Carballedo
Danuta
D
Lisiecka
Andrew
A
Fagan
Derek
D
Morris
Ciara
C
Fahey
Gary
G
Donohoe
James
J
Meaney
Michael
M
Gill
Thomas
T
Frodl
D000328:Adult; D001921:Brain / Q000473:pathology* / Q000502:physiology*; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics*; D055815:Young Adult
C571508:Bicc1 protein, human; D016601:RNA-Binding Proteins