Precision Medicine for Preventing Suicide

A team of researchers at Indianapolis-based Indiana University School of Medicine say they have created a novel method for diagnosing suicide risk by developing blood tests that work in everyone as well as more personalized blood tests for different subtypes of suicidality and high-risk groups.

The researchers also demonstrated how two apps, one based on a suicide-risk checklist and the other on a scale for measuring feelings of anxiety and depression, work along with the blood tests to increase the precision of tests and to propose potential lifestyle, psychotherapeutic, and other interventions. The team also noted that they were able to identify a series of medications and natural substances that could be developed for preventing suicide.

Their study (“Precision Medicine for Suicidality: From Universality to Subtypes and Personalization”) is published in Molecular Psychiatry.

“We sought to investigate whether blood gene expression biomarkers for suicide (that is, a ‘liquid biopsy’ approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings,” write the investigators.

“Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2).”

“Our work provides a basis for precision medicine and scientific wellness preventive approaches,” said Alexander B. Niculescu III, M.D., Ph.D., professor of psychiatry and medical neuroscience at IU School of Medicine and attending psychiatrist and research and development investigator at the Richard L. Roudebush Veterans Affairs Medical Center.

The multistep research approach began with serial blood tests taken from 66 people who had been diagnosed with psychiatric disorders, followed over time, and who had at least one instance in which they reported a significant change in their level of suicidal thinking from one testing visit to the next. Using the Niculescu group’s Convergent Functional Genomics approach, the team prioritized the candidate gene expression biomarkers that were best associated with suicidality in each individual and across individuals.

The researchers then tested the validity of the biomarkers using blood samples drawn from 45 people who had committed suicide. The biomarkers were subsequently tested in another group of individuals to determine how well they could predict which of them would report intense suicidal thoughts or would be hospitalized for suicide attempts.

The researchers identified RNA molecules as the biomarkers whose levels in the blood changed along with changes in the levels of suicidal thoughts experienced by the patients.

Among the findings reported in the current paper were:

“An algorithm that combines biomarkers with the apps that was 90 percent accurate in predicting high levels of suicidal thinking and 77 percent accurate in predicting future suicide-related hospitalizations in everybody, irrespective of gender and diagnosis.”

“A refined set of biomarkers that apply universally in predicting risk of suicide among both male and female patients with a variety of psychiatric illnesses, including new biomarkers never before linked to suicidal thoughts and behavior.”

“Four new subtypes of suicidality were identified (depressed, anxious, combined, and non-affective/psychotic), with different biomarkers being more effective in each subtype.”

“Biomarkers that were associated with specific diagnoses and genders, such as one, known as LHFP [lipoma HMGIC fusion partner], that appears to be a very strong predictor for depressed men.”

“Two of the biomarkers, APOE [apolipoprotein E] and IL6 [interleukin-6], have broad evidence for involvement in suicidality and potential clinical utility as targets for drug therapies, as well as suggest a neurodegenerative and inflammatory component to the predisposition to suicide. APOE is responsible for proteins involved with managing cholesterol and fats, and some forms of the gene have been strongly implicated as risks for Alzheimer’s disease. IL6 expresses proteins involved in the body’s inflammation response.”

“Potential drug therapies and natural substances for preventing suicide, using the blood biomarker signatures and bioinformatics approaches. They included medications already in use to treat psychiatric illnesses and drugs approved for other uses, such as the diabetes medication metformin.”

Dr. Niculescu points out that while suicide can impact individuals in all walks of life, he believes such tragedies can be averted.

“This landmark larger study breaks new ground, as well as reproduces in larger numbers of individuals some of our earlier findings,” he said.