Research Aims and Hypotheses: The aim of this proposal is to conduct a pilot PET neuroimaging study of Translocation Protein (TSPO), a marker of neuro-inflammation in the brain, in adults with current unipolar (non-psychotic) major depressive disorder (MDD) and hospitalization for a recent suicide attempt (SA+: n = 10) compared with similar MDD patients but without life history of SA+ or current SI+ (n = 10). Given evidence of chronic inflammation in the periphery, and evidence of activated gliosis in the brains of completed suicides in those with histories of SA+, we hypothesize that 11C-ER176 TSPO PET binding (VT; a marker of neuro-inflammation) will be higher in selected cortico-limbic brain regions (e.g., OFC, vmPFC, ACC, INS, HIPP, AMYG) in those with recent history of SA+ compared with similar age/sex matched MDD patients without history of either SA+ or SI+.
Sample: Twenty male and female with current unipolar (non-psychotic) major depressive disorder with (n = 10) and without (n = 10) recent history of SA+ will be studied.
Measures: Diagnoses will be made using the SCID for syndromal disorders and the SIDP for personality disorders. History of suicidal ideation and suicide attempt will be assessed using Self-Injurious Thoughts and Behaviors Interview-Revised (SITBI-R), Beck Scale for Suicide Ideation (BSSI), and Lethality of Suicide Attempt Rating Scale (LSARS). We will also assess variables in the ideation-to-action framework including: Cognition (Suicide Cognition Scale), Hopelessness (Beck Hopelessness Scale), Psychic Pain (Psychache Rating Scale), Connectedness (Interpersonal Needs Questionnaire), and capacity to attempt/complete suicide (Acquired Capability with Rehearsal for Suicide Scale). We will also assess state depression with the Hamilton Depression Rating Scale (HAMD-17). Aggression, anger, and impulsivity will also be assessed. Central neuro-inflammation will be assessed with PET scanning using 11C-ER176 as the radioligand for the Translocator Protein (TSPO) in the brain. Peripheral measures of inflammatory proteins will also be collected.
Procedures: Participants will be recruited from our psychiatric hospital (Harding Hospital). SA+ study patients will have a current unipolar (non-psychotic) major depressive disorder and a recent SA+ that led to hospitalization; comparison patients will be age/sex matched and also have current unipolar (non-psychotic) major depressive disorder will current history of SI+ but not life history SA+. Otherwise, all subjects will be/have: (a) Males or females age 21 years or older (if female, have a negative pregnancy test), (b) Current history of a unipolar (non-psychotic) major depressive disorder and, (c) Medically healthy. There will be two "visits". Visit 1 is for screening and assessment and Visit 2 is the 11C-ER176 PET Scan.
Impact: Demonstration that SA+ behaviors are related to the presence of neuro-inflammation in cortico-limbic brain regions will be an exciting development and suggest a new target for treatment and prevention of serious suicidal behavior.
Next Steps: If findings are positive, next steps include performing similar studies in a larger group of individuals with suicidal ideations and/or very recent suicide attempts and proof of concept trials to determine if neuro-inflammation can be reduced using therapies that are anti-inflammatory in nature.
