Early influence of the rs4675690 on the neural substrates of sadness

Background: CREB1 has previously been implicated in mood disorders, suicide, and antidepressant response. There is some evidence that the T allele in rs4675690, a single-nucleotide polymorphism near the CREB1 gene, is involved in the modulation of neural responses to negative stimuli. It is not known whether differential brain activity during negative mood state appears early in life in T allele carriers. Methods: Functional magnetic resonance imaging (fMRI) was used to measure brain activity, during a transient state of sadness, in children homozygous for the T allele or the C allele. This primary emotion was selected given that it is the prevailing mood in major depressive disorder (MDD). Blood-oxygen-level dependent (BOLD) signal changes were measured while subjects viewed blocks of neutral film excerpts and blocks of sad film excerpts. Results: There was significantly greater BOLD activation in the TT group, compared to the CC group, in the right dorsal anterior cingulate cortex (Brodmann area [BA 24]), right putamen, right caudate nucleus and left anterior temporal pole (BA 21), when the brain activity associated with the viewing of the emotionally neutral film excerpts was subtracted from that associated with the viewing of the sad film excerpts. Limitations: A replication study using larger samples may be required for more definitive conclusions. Conclusions: The different pattern of regional brain activation found here during transient sadness - in children carrying the T allele, compared to those carrying the C allele - might increase later in life susceptibility to emotional dysregulation and depressive symptoms. (C) 2011 Elsevier B.V. All rights reserved.