Spectroscopy markers of suicidal risk and mental pain in depressed patients

Prog Neuropsychopharmacol Biol Psychiatry. 2016 Oct 27;S0278-5846(16)30167-1. doi: 10.1016/j.pnpbp.2016.10.005. Online ahead of print.


Objective: Suicidal behavior has been associated with structural and functional impairments in neuroimaging studies, mainly localized in the prefrontal cortex. However, little is known of the in vivo biochemical alterations that could be markers of suicidal risk.

Methods: Proton magnetic resonance spectroscopy was used to measure at-rest levels of 9 metabolites (glutamate, glutamine, glutathione, GABA, N-acetylaspartate (NAA), N-acetylaspartylglutamate, myo-inositol, aspartate, total choline), in the right dorsal prefrontal cortex of 25 unmedicated depressed patients, including 15 with a history of suicidal behavior, and 33 healthy controls. We compared metabolite levels between groups, and run correlations with 9 clinical variables relevant for suicide risk.

Results: We found very significant associations between NAA levels and psychological pain measured by a simple analog scale (r=-0.47, p<10-3), and between choline levels and current suicidal ideas (r=0.53, p<10-3). These associations were independent from group, gender, age or depression level. While psychological pain and suicidal ideas were highly inter-correlated (r=0.61, p<10-3), the above-mentioned associations with compounds were independent. Mental pain was also correlated with Stroop interference, verbal fluency and (indirectly) decision-making, all cognitive measures previously associated with suicidal risk. Lower NAA levels, and higher glutamine levels were found in suicide attempters and in all patients relative to healthy controls, but these differences did not survive co-variation with age or Bonferroni's correction.

Conclusion: This preliminary study suggests that markers of impaired neuronal and glial functioning in right dorsal prefrontal cortex underlie cardinal symptoms of the suicidal crisis. Targeting this region may be relevant for the short-term suicidal prevention. This study also supports a dimensional perspective in research on suicidal behavior.

Keywords: Depression; Prefrontal cortex; Psychological pain; Spectroscopy; Suicide attempt.