It may one day be possible to identify and treat those at risk for suicide based on gene expressions of elevated blood biomarkers, researchers suggested.
In a cohort of 42 bipolar patients, the nine who had a dramatic shift from no suicidal thoughts to strong suicidal ideation also had marked increases in levels of SAT1 (spermidine/spermine N1–acetyltransferase 1), as well as other RNA biomarkers, Alexander B. Niculescu III, MD, PhD, director of the Laboratory of Neurophenomics at the Institute of Psychiatric Research at the Indiana University School of Medicine, and colleagues reported online in Molecular Psychiatry.
They validated the findings in a post-mortem analysis of nine age-matched suicides, as well as longitudinally in a group of 46 patients with schizophrenia or schizoaffective disorder.
In the longitudinal follow-up of the 46 with psychosis, high blood levels of the biomarkers were correlated with future suicide-related hospitalizations, as well as hospitalizations that had occurred before the blood tests.
Niculescu and colleagues suggested that these markers reflect more than just a current state of high risk, but could be trait markers that correlate with long-term risk.
“Taken together, our results have implications for the understanding of suicide, as well as for the development of objective laboratory tests and tools to track suicidal risk and response to treatment,” they concluded.
To reach their conclusions, the investigators followed the 42 bipolar patients over a 3-year period, taking blood samples and performing a system of genetic and genomic analysis called Convergent Functional Genomics that identified and prioritized the best markers by cross-validation with other lines of evidence.
The strongest biological “signal” associated with suicidal thoughts was the marker SAT1.
“Remarkably, we found SAT1 gene expression levels to be elevated in nine out of nine (100%) subjects who committed suicide that we tested,” researchers wrote.
The increase in the biomarker was at least three standard deviations above the average levels in the high suicidal ideation participants, “which constitutes a very stringent threshold for use as a predictive biomarker.”
In the validation cohort, high levels of SAT1 gene expression were associated with suicidal thoughts, delusions, mood disorders, anxiety, hallucinations, and stress.
Others strong RNA biomarkers discovered and validated include:
- PTEN (phosphatase and tensin homolog)
- MARCKS (myristoylated alanine-rich protein kinase C substrate)
- MAP3K3 (Mitogen-activated protein kinase kinase kinase 3)
The omega-3 docosahexaenoic acid (DHA) signaling pathway stood out as a potential underlying mechanism involved in the biomarkers.
“Low omega-3 levels have been correlated with increased suicidality in human epidemiological studies,” Niculescu and colleagues noted.
They pointed out that SAT1 and 18 other biomarkers identified in the current study had been found to change “in expression by omega-3 treatment in the blood of the circadian clock gene DBP (D-box binding protein)” in mice.
Further, the current study identified DBP as a biomarker that is decreased in high suicidal states, and previous work by these researchers “implicated DBP in mood disorders, psychosis, alcoholism, and anxiety disorders.”
The suicide biomarker PTEN — identified longitudinally and in suicide victims in the current study — had previously been shown to be decreased in mice that lacked DBP. When treated with omega-3 fatty acids, however, the mice reverted back to a normalized phenotype.
Earlier this year, researchers from the Massachusetts General Hospital found that bipolar disorder, schizophrenia, ADHD, and major depressive disorder share common genetic underpinnings — despite having different symptoms and disease courses.
A meta-analysis from Italian researchers found that lithium lowered suicide risk in those with mood disorders.
In the study, all participants and suicide victims were male and all but one were white, which could limit the generalizability of the findings. The researchers called for more extensive, normative studies in the population at large.
Patients for the study were recruited from the Indianapolis VA Medical Center, the Indiana University School of Medicine, and various facilities that serve people with mental illnesses in Indiana. The nine suicide victims were obtained through the local Marion County coroner’s office.
Because people who commit suicide are often driven by unknown biological processes, these findings offer hope in identifying those at risk and getting them preventive treatment. — Sanjay Gupta, MD
Connie’s comments: In utero, our brain is developed with proper nutrients or affected by outside forces such as drugs, and quality of sperm and egg. Outside, we are bombarded by toxins in our diet and environment. Sleeping late, drinking alcohol, combo of drug overdose and other stressors affect our brain. It is known that a mother’s loving care can alter our cells toward favorable growth. But our brain is very much affected by many imbalance in body chemistry from the moment we are conceived to the time we overdose with meds or drugs. Care for our bodies and babies, brain development starts there from breastfeeding to baby massage and child rearing. Our loving care can make a difference but our brain chemicals are the final arbiters of our faith. Take care of our bodies, our brain especially.
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