Connecting inflammation with glutamate agonism in suicidality.
Level 4 - case-series / case-control
Case-control study comparing suicide attempters to controls with a follow-up subset
PubMed 23299933 · doi:10.1038/npp.2012.248
What was done
The authors measured quinolinic acid (QUIN, an NMDA receptor agonist) and kynurenic acid (KYNA, an NMDA receptor antagonist) in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls using gas chromatography mass spectrometry and high-performance liquid chromatography. Interleukin-6 (IL-6) levels were also measured in CSF. Participants were assessed with the Suicide Intent Scale and the Montgomery-Asberg Depression Rating Scale (MADRS). A subset of patients underwent follow-up lumbar punctures within 6 months.
What was found
CSF QUIN was significantly elevated in suicide attempters compared to controls (P < 0.001), while KYNA was not significantly different. Elevated QUIN was associated with higher CSF IL-6 levels and positively correlated with Suicide Intent Scale total scores. QUIN decreased significantly in patients tested at follow-up within 6 months. Exact baseline concentrations, correlation coefficients, and follow-up sample sizes were not reported in the abstract.
Why it matters
This study provides direct clinical evidence in human CSF connecting central nervous system inflammation and NMDA-receptor glutamatergic agonism to suicidal behavior, offering a potential biological mechanism for the rapid anti-suicidal effects of NMDA antagonists like ketamine.
Limits
The study is observational and cannot demonstrate a causal link. The total sample size is relatively modest (n = 100), the number of follow-up patients is not stated, and the abstract omits point estimates, confidence intervals, and correlation coefficients.
Cited by
- supports A study found that suicide attempters had up to 300% elevated levels of quinolinic acid in their cerebrospinal fluid.