Association of a Polymorphism Near CREB1 With Differential Aversion Processing in the Insula of Healthy Participants

Abstract

Context Previous functional neuroimaging studies have identified a network of brain regions that process aversive stimuli, including anger. A polymorphism near the cyclic adenosine monophosphate response element binding protein gene (CREB1) has recently been associated with greater self-reported effort at anger control as well as risk for antidepressant treatment–emergent suicidality in men with major depressive disorder, but its functional effects have not been studied. Objective To determine whether this genetic variant is associated with altered brain processing of and behavioral avoidance responses to angry facial expressions. Design and Participants A total of 28 white participants (mean age, 29.2 years; 13 women) were screened using the Structured Clinical Interview for DSM-IV to exclude any lifetime Axis I psychiatric disorder and were genotyped for rs4675690, a single-nucleotide polymorphism near CREB1. Main Outcome Measures Blood oxygenation level–dependent signal by functional magnetic resonance imaging in the amygdala, insula, anterior cingulate, and orbitofrontal cortex during passive viewing of photographs of faces with emotional expressions. To measure approach and avoidance responses to anger, an off-line key-press task that traded effort for viewing time assessed valuation of angry faces compared with other expressions. Results The CREB1-linked single-nucleotide polymorphism was associated with significant differential activation in an extended neural network responding to angry and other facial expressions. The CREB1-associated insular activation was coincident with activation associated with behavioral avoidance of angry faces. Conclusions A polymorphism near CREB1 is associated with responsiveness to angry faces in a brain network implicated in processing aversion. Coincident activation in the left insula is further associated with behavioral avoidance of these stimuli.

Preliminary investigation of the influence of CREB1 gene polymorphisms on cognitive dysfunction in Chinese patients with major depression

“…A study by Juhasz and colleagues showed that CREB can amplify the effect of childhood adversity and increase the risk of MDD [59]. Perlis and colleagues showed that CREB is associated with responsiveness to angry faces in a brain network implicated in processing aversion [60]. These networks develop through interactions with the environment; the neuronal structure and neurotransmission in these networks are constantly being refined through activity-dependent synaptic plasticity in order to optimally process and store relevant information.…”

Altered Neural Processing to Social Exclusion in Young Adult Marijuana Users

“…MJ scored greater on peer conformity on the MISS than CON (t (1,40) = 2.08, p = 0.044; Fig 2A), and showed a trend toward higher ratings on overall suggestibility, (t (1,40) = 1.96, p = 0.057), though it should be noted that these differences were not significant when corrected for multiple comparisons, ans should be followed up with larger samples for confirmation. Across groups, peer conformity scores were positively associated with vACC activation ( r 2 = 0.10, p = 0.042; Fig 2B).…”

“…We did not extract data from the OFC because neither group showed significant activation in this region. Individual parameter estimates were extracted using the FSL program featquery (http://fsl.fmrib.ox.ac.uk/fsl/fsl4.0/feat5/featquery.html) from anatomical ROIs using masks parcellated from the ICBM152 T1 brain at the MGH Center for Morphometric Analysis (CMA) (39, 40). Values were regressed against peer influence scores, in order to investigate whether brain activation was associated with trait levels of peer conformity.…”

Neural mechanisms of sensitivity to peer information in young adult cannabis users

“…Activation signal was extracted from using the following steps: (1) the signal at each voxel was converted to a (percentage) deviation from the mean for that voxel across the entire time series, (2) the signal was averaged by stimulus type and spatially translated into MNI space, and (3) anatomical masks were designated consisting of the volume of interest through which each individual participant's data was extracted. All masks were parcellated from the ICBM152 T1 brain at the MGH Center for Morphometric Analysis (CMA) (Gasic et al, 2009; Perlis et al, 2008), using validated anatomical landmarks for the NAc and caudate.…”