Project 1

Neurobiology of Suicide: Childhood Adversity, Neuroinflammation and Genomics

Childhood adversity is associated with greater risk for depression in adulthood, aggressive traits and suicide. Adversity, whether in childhood or in adulthood, can be a severe stress that can cause neuroinflammation, which can also lead to increased risk for suicide.

The biological basis of this relationship is mostly unknown, but increased neuroinflammatory cytokines in suicidal individuals who report childhood adversity is reported in the literature.

Stress and suicide are also associated with having fewer neurons in parts of the brain and nerve process shrinkage in the prefrontal cortex and hippocampus. Smaller hippocampus volume is a risk factor for stress-related psychopathology.

In addition, we often find that depressed individuals who suicide show lower serotonin transporter (5-HTT) and higher postsynaptic serotonin 1A receptor (5-HT_1A) binding in the prefrontal cortex and a higher rate of childhood adverse events. We hypothesize that a combination of genes, environment and epigenetic effects can produce a neurobiological phenotype of suicide risk.

What Postmortem Brain Can Tell Us About Links Between Childhood Adversity, Neuroinflammation and Suicide

The project is designed to determine whether reported childhood adversity is associated with elevated proinflammatory cytokines in the prefrontal cortex in 5 groups of age- and sex-matched depressed suicides; nonpsychiatric controls with and without reported childhood adversity; and depressed individuals with no history of suicide attempts, postmortem. We will specifically examine prefrontal cortex and hippocampus for neuroplasticity deficits.

We aim to:

• test whether childhood adversity and suicide are associated with elevated proinflammatory markers and more neurons and glia labeled with inflammatory markers compared to controls and resilient subjects.
• determine whether the neuro-inflammation is associated with more activated microglia, and
• measure dendrite length and neuronal branching as anatomical indices of neuropathology.