The Friedman Brain Institute

The Psychiatric Genomics Consortium Suicide Working Group (PGC SUI) is a multi-disciplinary team of scientists and clinicians from more than 20 countries worldwide. Suicidal ideation, suicide attempt and suicide (collectively “suicidality”) have partially genetic underpinnings, which are somewhat distinct from the genetic basis of related psychiatric disorders. PGC SUI combines genetic data from cohorts globally, to conduct large-scale analyses of the genetic etiology of suicidality, such that the underlying biology, and opportunities for novel treatments can be better understood.

Scientists in this research area include:

• Niamh Mullins, PhD
• Fatemeh Haghighi, PhD

Converging evidence shows associations between neuro and peripheral inflammation in suicide. Molecular abnormalities in suicide are investigated in postmortem brain cases of suicide decedents and controls through epigenetic and transcriptional studies of glial cells (specifically microglia and oligodendrocytes) as well as the neurovascular unit involved in neuroimmune processes. Such suicide associated transcriptional regulatory alterations and corresponding genes are then examined in the Million Veteran Program (MVP) cohort using data from at-risk participating Veterans with history of suicidal behavior to identify genetic variants that contribute to suicide risk for use in development of suicide risk prediction models.

Scientists in this research area include:

• Fatemeh Haghighi, PhD

Individuals with major depressive disorder (MDD) face a significantly higher risk of dying by suicide compared to the general population. Historically, most neurobiological investigations into MDD and suicide have focused on neuronal dysfunction. Yet, recent evidence highlights the potential role of microglia (MG) — the brain's immune cells — in the etiology of these conditions. We've pioneered a fluorescence-activated nuclear-sorting (FANS) protocol, which facilitates the isolation of nuclei from the four major brain cell types, MG included, from frozen autopsied human brains. Using this FANS protocol and samples from a large cohort of donors with MDD (who died either by suicide or other causes) as well as from control donors without notable psychiatric histories, our project aims to uncover the intricate specifics of MG perturbations in MDD and suicide. We're achieving this by integrating GWAS, MG eQTLs, and epigenetic maps of enhancers that are active in MG. Ultimately, our findings are poised to identify MDD and suicide risk variants and the affected genes that are likely to be causal for these disorders and act specifically in MG cells.

Scientists in this research area include:

• Stella Dracheva, PhD
• Alexey Kozlenkov, PhD

The Suicide Research and Prevention Lab at Mount Sinai, led by Dr. Galynker, is committed to advancing our understanding of Suicide Crisis Syndrome (SCS), an acute suicidal cognitive-affective state predictive of imminent suicidal behaviors. The lab is dedicated to investigating the intricate mechanisms underlying how individuals with heightened vulnerability to suicide develop Suicidal Narratives and Suicide Crisis Syndrome when confronted with stressful life circumstances. Current projects are centered around three main areas: the dissemination of novel suicide risk assessment tools, the development of treatment protocols for managing Suicide Crisis Syndrome, and the creation of cutting-edge AI-based training resources. These resources aim to enhance clinicians’ proficiency in managing negative emotional responses when working with patients at risk of suicide.   

Selected Projects:

The Time Course of Emotional Distress Prior to Suicidal Behavior

Psychopharmacological Treatment of Emotional Distress Experienced Prior to Suicidal Behavior: a Randomized Controlled Study

Inpatient Implementation of Suicide Crisis Inventory and Suicide Crisis Syndrome-Checklist for Clinical Use

Impact of Clinician Virtual Human Interaction Training in Emotional Self-Awareness on Patients’ Suicidal Ideation and Suicide Crisis Syndrome: a Randomized Controlled Trial

Scientists in this research area include:

• Igor Galynker, MD, PhD
• Lisa J. Cohen, PhD
• Sarah Bloch-Elkouby, PhD
• Rawad El Hayek, MD
• Martina Sobrero, MD

The challenge of addressing acute suicidal ideation in depressed patients has grown considerably in contemporary healthcare. Despite the availability of efficacious treatments, the actual treatment rendered to patients once serious suicidal thinking sets in leaves much to be desired. The prevailing healthcare approach of the suicidal patient has traditionally leaned toward admission to inpatient care and a trial of antidepressants, which can take weeks to have an effect. Among the potential efficacious treatments that rapidly reverse suicidal thinking, both electroconvulsive therapy (ECT) and subanesthetic dose intravenous ketamine stand out. Yet, their underutilization stems from an absence of comprehensive comparative research, leading to clinician hesitancy, patient apprehension, and restricted resources from hospital management and payment providers. Addressing this gap, we are participating in a multi-site study that endeavors to conduct a large-scale, non-inferiority randomized trial comparing ECT and ketamine’s efficacy for rapid reversal of acute suicidality in depression across various age groups.

Scientists in this research area include:

• James Murrough, MD, PhD