Lower CSF MHPG predicts short-term risk for suicide attempt
Open accessAbstract
Post-mortem studies document alterations in the central noradrenergic system in suicide. However, studies of non-fatal suicide attempts have, thus far, found no consistent relationship to the noradrenaline metabolite 3-methoxy-4-hydroxphenylglycol (MHPG) in cerebrospinal fluid (CSF). We therefore conducted a prospective study of CSF MHPG and suicidal acts in major depression and bipolar depression. CSF MHPG was assayed in 184 drug-free patients with DSM-IV major depressive disorder or bipolar disorder, presenting for treatment of a current depressive episode, who were then followed-up for up to 12 months. Survival analysis was conducted using Cox proportional hazards modelling to test association of CSF MHPG and future suicidal behaviour, and potential clinical mediators. Twenty-seven individuals made a suicide attempt (two fatal) in the follow-up period. Lower CSF MHPG predicted future suicide attempt or suicide (22% increase in hazard for each 10 pmol/ml lower MHPG, p=0.045). Lower CSF MHPG also correlated with higher medical lethality of future suicidal act (mean MHPG: 49+/-18 vs. 32+/-12 pmol/ml for low- vs. high-lethality, t=2.8, d.f.=25, p=0.009). Smoking and self-rated depression severity were also associated with lower CSF MHPG and with future suicide attempt, but were not statistically significant mediators in multivariate models. In conclusion, lower CSF MHPG is associated with short-term risk for future suicidal behaviour in the 12 months following a major depressive episode. Psychopathology that mediates the relationship between lower CSF MHPG and future suicidal behaviour needs to be identified.
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Excessive norepinephrine release combined with fewer noradrenergic neurons may result in depletion of norepinephrine and lower CSF MHPG in future suicide attempters.
“Perhaps this excessive norepinephrine release, when combined with fewer noradrenergic neurons, is more likely to result in a depletion of norepinephrine and lower CSF MHPG in future suicide attempters (127).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [127]
Depressed suicide attempters have lower urinary and plasma MHPG than controls, and CSF MHPG levels correlate negatively with lethality of future suicide attempts.
“Moreover, depressed suicide attempters have lower urinary and plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHGP), a major metabolite of norepinephrine, compared with control subjects, and CSF 3-methoxy-4-hydroxphenylglycol (MHPG) levels correlate negatively with lethality of future suicide attempts (127).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [127]
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Self-citation
- Authors
- Galfalvy, H., Currier, D., Oquendo, M. A., Sullivan, G., Huang, Y.-Y., & John Mann, J.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Galfalvy, Hanga
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-07-02
- Volume
- 12
- Issue
- 10
- Pages
- 1327
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC3773850
- OpenAlex
- W2155063213
- Cited by
- 38
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 62185, MH074068, R01MH048514, K25MH074068, P50MH062185)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- suicide attempts, suicidal behavior, noradrenergic system, noradrenaline metabolites, major depressive disorder, bipolar depression, suicide risk prediction, smoking, depression severity
- MeSH terms
- Adult, Bipolar Disorder, Major Depressive Disorder, Female, Follow-Up Studies, Humans, Male, Methoxyhydroxyphenylglycol, Middle Aged, Predictive Value of Tests, Prospective Studies, Risk Factors, Suicide, Attempted, Time Factors, Cohort Studies, Biomarkers
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