Postmortem anterior cingulate lipid composition in people who died by suicide: exploratory multivariate findings shaped by age and environmental factors.
6 affiliations
- 1Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland. [email protected].
- 2Laboratory of Chemical Hazards in the Environmental, Department of Environmental Analytics, University of Gdańsk, Gdańsk, Poland.
- 3Department of Pharmaceutical Biochemistry, Medical University of Gdańsk, Gdańsk, Poland.
- 4Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany.
- 5Institute of Nursing and Medical Rescue, State University of Applied Sciences, Koszalin, Poland.
- 6Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland.
Abstract
Suicide is a major public health concern, and lipid metabolism has been implicated in its neurobiology. We profiled fatty-acid composition in bilateral pregenual anterior cingulate cortex (ACC) samples obtained at forensic autopsy from 98 individuals (42 who died by suicide, 56 sudden-death controls) using targeted GC-MS and centered log-ratio (CLR) transformation. Analyses included exploratory univariate tests, covariate-adjusted linear mixed models (LMMs; FDR correction), and Bayesian Additive Regression Trees (BART) classification. Univariate tests showed nominal case-control differences in cholesterol and several n-6 PUFAs, but no lipid showed a significant main group effect after covariate-adjusted LMMs with FDR correction. Age and season were more consistent correlates of ACC lipid composition. In the full sample, a complete-case lipids-only BART model achieved CV-BCA = 72.0 ± 5.1% (n = 81; permutation p < 0.001), but interpretation was limited by different analytic samples across model types. In an adult-only sensitivity analysis (age ≥18 years; n = 92), covariate-adjusted LMMs again showed no FDR-significant group effects, whereas an exploratory mixed BART model (sex, age, PMI, ECFA 20:0, DPAn-6, EPA; n = 75 complete cases) achieved CV-BCA = 75.5 ± 3.7% and nested CV-BCA = 73.5 ± 13.3%. These findings do not support robust single-lipid suicide-associated biomarkers. Rather, they suggest that ACC lipid signals are subtle, multivariate, and strongly shaped by demographic, seasonal, and postmortem factors. The study provides a methodological caution for postmortem lipidomics and requires external validation in clinically characterized cohorts.
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BibTeX
@article{karnecki2026postmortem,
title = {{Postmortem anterior cingulate lipid composition in people who died by suicide: exploratory multivariate findings shaped by age and environmental factors.}},
author = {Karol Karnecki and Adriana Mika and Tomasz Śledziński and Johann Steiner and Henrik Dobrowolny and Julian Świerczyński and Marta Krzyżanowska and Gracjana Stachewicz and Monika Czapiewska and Justyna Korczyńska and Tomasz Gos},
journal = {Translational psychiatry},
year = {2026},
month = aug,
doi = {10.1038/s41398-026-04393-9},
url = {https://europepmc.org/article/MED/43009460},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Postmortem anterior cingulate lipid composition in people who died by suicide: exploratory multivariate findings shaped by age and environmental factors.
AU - Karol Karnecki
AU - Adriana Mika
AU - Tomasz Śledziński
AU - Johann Steiner
AU - Henrik Dobrowolny
AU - Julian Świerczyński
AU - Marta Krzyżanowska
AU - Gracjana Stachewicz
AU - Monika Czapiewska
AU - Justyna Korczyńska
AU - Tomasz Gos
PY - 2026
DA - 2026/08/15
JO - Translational psychiatry
DO - 10.1038/s41398-026-04393-9
UR - https://europepmc.org/article/MED/43009460
AB - Suicide is a major public health concern, and lipid metabolism has been implicated in its neurobiology. We profiled fatty-acid composition in bilateral pregenual anterior cingulate cortex (ACC) samples obtained at forensic autopsy from 98 individuals (42 who died by suicide, 56 sudden-death controls) using targeted GC-MS and centered log-ratio (CLR) transformation. Analyses included exploratory univariate tests, covariate-adjusted linear mixed models (LMMs; FDR correction), and Bayesian Additive Regression Trees (BART) classification. Univariate tests showed nominal case-control differences in cholesterol and several n-6 PUFAs, but no lipid showed a significant main group effect after covariate-adjusted LMMs with FDR correction. Age and season were more consistent correlates of ACC lipid composition. In the full sample, a complete-case lipids-only BART model achieved CV-BCA = 72.0 ± 5.1% (n = 81; permutation p < 0.001), but interpretation was limited by different analytic samples across model types. In an adult-only sensitivity analysis (age ≥18 years; n = 92), covariate-adjusted LMMs again showed no FDR-significant group effects, whereas an exploratory mixed BART model (sex, age, PMI, ECFA 20:0, DPAn-6, EPA; n = 75 complete cases) achieved CV-BCA = 75.5 ± 3.7% and nested CV-BCA = 73.5 ± 13.3%. These findings do not support robust single-lipid suicide-associated biomarkers. Rather, they suggest that ACC lipid signals are subtle, multivariate, and strongly shaped by demographic, seasonal, and postmortem factors. The study provides a methodological caution for postmortem lipidomics and requires external validation in clinically characterized cohorts.
SN - 2158-3188
ER -