Suicide, the desperate last action of the despairing, is almost always the product of substance abuse, financial or family difficulties, or illness – and most often some combination of those factors.

But at the level of minute DNA expression, there is also an epigenetic factor appearing in the blood of those who have attempted suicide, according to a new study by Swedish scientists published in the journal EBioMedicine.

“Our results show epigenetic changes in the CRH gene related to severity of suicide attempt in adults and a general psychiatric risk score in adolescents,” study authors write. “Significant blood-brain correlations in methylation suggest these alterations may impact on expressional profile of CRH in the brain.”

Blood was drawn from 88 individuals from the Suicide Prevention Clinic at the Karolinska University Hospital. The DNA samples were then analyzed using the EZ DNA Methylation Gold kit from ZymoResearch to convert the data to biosulfite readings. Those readings were then assessed on the Illumina Infinium Methylation EPIC BeadChip. The 88 samples were divided into high- and low-risk groups based on their suicidal severity (comparing violent and non-violent methods of taking their own lives).

Those 88 adult patients were also compared to previous, and bigger, cohort studies of younger adolescents: one containing 129 and another encompassing the DNA of 93 teens, aged 14 to 17. 

The theory, presented by the Swedish authors and other teams of scientists over the last decade, is that suicidal behavior and attempts were linked to cortisol stress response in the body. One particular pathway is the corticotropin releasing hormone, or CRH, gene.

Their results appear to confirm the link. Reduced expression of the CRH gene was associated with negative prognosis. The high-risk teens showed psychiatric risk for suicide, as well as the adults who had tried most seriously to kill themselves by violent means.

The scientists from Umea University, Uppsala University and the Karolsinka Institutet added, however, that the latest study did not show any causative effects.

“Our environment affects our genetic expression, which is usually referred to as epigenetic change,” said Jussi Jokinen, professor of psychiatry at Umea University, lead author of the study. “Even if we aren’t able to draw distinct parallels between the findings in these cohort studies, our results still point toward the importance of an optimal regulation of the stress system for psychiatric illness.”

Ultimately, four of the patients from the original 88 killed themselves: three by hanging, and one by overdose.

Other studies have sought the secret to suicide in the biochemical makeup of the despairing. A study backed by the U.S. Department of Veterans Affairs in October 2016 found that a key enzyme in the cerebrospinal fluid could be both be an indicator and treatment target for suicide and severe depression, for example.