In the Journals

Genetic changes relate to severity of suicide attempt, psychiatric risk

Genetic changes in the gene that affects stress regulation – known as the corticotropin-releasing hormone, or CRH, gene – were associated with severity of suicide attempt in adults and psychiatric risk in adolescents, according to study findings.

“The cortisol stress response is one of the most promising candidate suicide endophenotypes,” Jussi Jokinen, MD, PhD, professor in psychiatry at Umeå University in Sweden, and colleagues wrote. “Genetic studies point to significant associations between [FK506-binding protein 51 (FKBP5)] and [corticotropin-releasing hormone receptor (CRHR1)] genes and a high rate of attempted suicide and some genetic studies have reported that [corticotropin releasing hormone binding protein (CRHBP)] and FKBP5 genes interact with childhood trauma to increase the risk for suicidal behavior.”

Using blood samples from 88 participants who attempted suicide, researchers sought to detect hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG sites that showed changes in DNA methylation in stress system-related genes linked to severity of the attempt. They included CpG sites of specific HPA-axis coupled genes, such as CRH, CRHBP, CRHR1, corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). The researchers also examined these genetic changes in relation to general psychiatric risk in two cohorts of teenagers aged 14 to 17 years (n = 222). Then, the investigators divided all participants into high- and low-risk groups based on the severity of their suicidal behavior and assessments of their psychiatric symptoms.

The methylation state of two CRH-associated CpG sites (cg19035496 and cg23409074) were linked to a significant decrease in the epigenetic methylation in the 31 high-risk suicide attempters (P<.001). Although the first cohort of adolescents showed no association between DNA methylation of CpG sites and the general psychiatric risk, cg19035496 was hypermethylated among teens in the second cohort who were at high psychiatric risk (P < .01). These results demonstrate that epigenetic changes in the CRH gene relate to severity of suicide attempt in adults and were more prevalent in adolescents with an increased risk for psychiatric illness, according to the authors.

"Since psychiatric illness is a serious and growing public health problem, it's important that we take early signs of psychiatric illness and suicidal behavior into consideration in suicide prevention," Jokinen said in a press release. "Our environment affects our genetic expression, which is usually referred to as epigenetic change. Even if we aren't able to draw distinct parallels between the findings in these cohort studies, our results still point towards the importance of an optimal regulation of the stress system for psychiatric illness." – by Savannah Demko

Disclosures: The authors report funding for this study from the Swedish Research Council, the Swedish Brain Research Foundation, a regional agreement between Umeå University and Västerbotten County Council and grants provided by the Stockholm County Council.

Genetic changes in the gene that affects stress regulation – known as the corticotropin-releasing hormone, or CRH, gene – were associated with severity of suicide attempt in adults and psychiatric risk in adolescents, according to study findings.

“The cortisol stress response is one of the most promising candidate suicide endophenotypes,” Jussi Jokinen, MD, PhD, professor in psychiatry at Umeå University in Sweden, and colleagues wrote. “Genetic studies point to significant associations between [FK506-binding protein 51 (FKBP5)] and [corticotropin-releasing hormone receptor (CRHR1)] genes and a high rate of attempted suicide and some genetic studies have reported that [corticotropin releasing hormone binding protein (CRHBP)] and FKBP5 genes interact with childhood trauma to increase the risk for suicidal behavior.”

Using blood samples from 88 participants who attempted suicide, researchers sought to detect hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG sites that showed changes in DNA methylation in stress system-related genes linked to severity of the attempt. They included CpG sites of specific HPA-axis coupled genes, such as CRH, CRHBP, CRHR1, corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). The researchers also examined these genetic changes in relation to general psychiatric risk in two cohorts of teenagers aged 14 to 17 years (n = 222). Then, the investigators divided all participants into high- and low-risk groups based on the severity of their suicidal behavior and assessments of their psychiatric symptoms.

The methylation state of two CRH-associated CpG sites (cg19035496 and cg23409074) were linked to a significant decrease in the epigenetic methylation in the 31 high-risk suicide attempters (P<.001). Although the first cohort of adolescents showed no association between DNA methylation of CpG sites and the general psychiatric risk, cg19035496 was hypermethylated among teens in the second cohort who were at high psychiatric risk (P < .01). These results demonstrate that epigenetic changes in the CRH gene relate to severity of suicide attempt in adults and were more prevalent in adolescents with an increased risk for psychiatric illness, according to the authors.

"Since psychiatric illness is a serious and growing public health problem, it's important that we take early signs of psychiatric illness and suicidal behavior into consideration in suicide prevention," Jokinen said in a press release. "Our environment affects our genetic expression, which is usually referred to as epigenetic change. Even if we aren't able to draw distinct parallels between the findings in these cohort studies, our results still point towards the importance of an optimal regulation of the stress system for psychiatric illness." – by Savannah Demko

Disclosures: The authors report funding for this study from the Swedish Research Council, the Swedish Brain Research Foundation, a regional agreement between Umeå University and Västerbotten County Council and grants provided by the Stockholm County Council.