A pilot study of differential brain activation to suicidal means and DNA methylation of CACNA1C gene in suicidal attempt patients

Suicide is a serious public health problem. In this study, we investigated functional brain changes to novel visual stimuli of suicidal means, DNA methylation status, and the relationship between the two markers. 14 suicidal attempt patients (SAs) and 22 healthy controls were included. Pictures of facial expressions and suicidal means were shown to subjects during fMRI scanning. 11 CpG sites within transcription factor binding site of CACNA1C gene were selected. In knives (K) vs. natural landscape (NL) condition, left middle frontal gyrus (Brodmann's area, BA 6 and 46) and left inferior frontal gyrus (BA 9) were shown to be significantly higher brain activation in the SAs than the controls (p<0.001). DNA methylation percentages of CpG site 4 (p=0.005) and 6 (p=0.037) were found to be related to the SAs. In the SAs, methylation degree of site 4 and site 6 was positively correlated with signal intensity of K vs. NL condition in left thalamus. The degree of site 4 was positively correlated with signal intensity in left middle and inferior frontal gyri in SAs. The possibility that these findings might be involved in the neurobiology of suicidal behavior is suggested.