Détails sur le projet
Description
Project Summary
Suicide is a leading cause of premature death in the United States (US). Convergent evidence across
genetic, postmortem, and immunohistochemical studies suggest a role for altered glutamate (Glu)—the
amino acid neurotransmitter that mediate most of the brain's fast excitatory transmission—in the
pathogenesis of suicide. Still, there is little research to-date on brain glutamate concentrations measured in
vivo in suicidal populations. Moreover, no study has examined alterations in activity-dependent dynamic
glutamate responses underlying mood- and cognition-related risk factors for suicide. This K08 project will
use magnetic resonance spectroscopy (MRS) to quantify in vivo steady-state Glu concentrations and
dynamic glutamate responses in n=70 currently depressed participants with and without a history of suicidal
behavior (MDD+SA and MDD-SA, respectively) and n=30 healthy volunteers (HV). Steady-state Glu will be
imaged across the length of the brain using MR spectroscopy imaging (MRSI). We will also use functional
MRS (fMRS) to detect activity-dependent changes in glutamate. Participants will complete two functional
tasks during MRS scanning: a pain-inducing cold pressor task (CPT) and a neurocognitive task (Stroop);
and dynamic glutamate activity (GluΔ) will be measured in response to these tasks. The group design will
allow us to parse suicide- and depression-related alterations in Glu signaling. Salivary cortisol
measurements will be obtained before and after the MRS scan. Participants will also complete seven days
of ecological momentary assessment (EMA) during which they will report on suicidal ideation, affect, and
stressors, six times daily. This will allow evaluation of the relationship between Glu signaling and
vulnerability to stress-related suicidal ideation/mood symptoms in daily life. We hypothesize that MDD+SAs
will exhibit altered cortical Glu concentrations and attenuated responses to physical pain stimulation,
compared with MDD-SAs and HVs. We will also evaluate whether dynamic glutamate responses to
functional tasks are associated with subjective pain responses, neurocognitive performance, cortisol stress
reactivity, and behavioral responses to naturalistic stressors. Understanding the contribution of altered brain
glutamate to suicide risk may help to facilitate development of pharmacological treatments that can
overcome limitations of existing monoamine-focused antidepressants currently used for treatment of suicide
risk.
Statut | Actif |
---|---|
Date de début/de fin réelle | 9/5/24 → 8/31/25 |
Keywords
- Psiquiatría y salud mental
Empreinte numérique
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