2026 ECNP Congress

PS02-2067

Association between folic acid prescription and suicide deaths among young adults in Sweden

Jussi Jokinen — A. Mert, A. Desai Boström · Karolinska Institutet, Clinical Neuroscience, Stockholm, Sweden

2026 ECNP Congress

Folic acid plays a central role in one-carbon metabolism and methylation processes required for the synthesis of monoamine neurotransmitters in the central nervous system. Folate may exert anti-inflammatory and neuroprotective effects through mechanisms involving homocysteine metabolism and modulation of neuroinflammatory pathways [1]. Given the growing evidence of linking systemic inflammation to suicidal behavior, alterations in folate status may therefore be relevant to biological pathways underlying both depression and suicide risk [2]. Importantly, low serum folate levels have been independently associated with both prior suicide attempts and current suicidal ideation severity in patients with depression [3]. However, evidence regarding folic acid supplementation as an adjunctive treatment in depressive disorders remains mixed. Nevertheless, some observational evidence suggests potentially beneficial associations. In a cross-sectional analysis of over 24,000 adults, individuals in the highest quartile of folic acid intake demonstrated a 38% lower odds of suicidal ideation, though Mendelian randomization analysis did not support a causal relationship [4]. Furthermore, Gibbons et al. previously demonstrated negative associations between folic acid prescription fills and suicide attempts and intentional self-harm among privately insured US adults, suggesting that folic acid may represent an inexpensive and widely available suicide prevention strategy [5]. However, that study examined intermediate outcomes such as suicidal ideation or attempts rather than suicide mortality, and population-level evidence examining the association between folic acid use and completed suicide remains limited.

OBJECTIVE: This study examined nationwide associations between folic acid fills and suicide death rates in 20-24-year-olds across the 21 Swedish regions during 2006-2021.

METHODS: Nationwide registers in Sweden were used to compare year-wise excess suicide mortality (ESM) and dispensations for folic acid (ATC-code: B03BB01) in 20-24- and 25-29-year-olds. ESM was defined as the regional yearly proportion of suicide-related deaths in 20-24-year-olds compared to the total of such deaths for the 20-29-year-olds. Associations between regional year-wise ESM and folic acid dispensation rates were analyzed by sex-stratified generalized linear mixed effect models (GLMM), modeled on the beta-binomial distribution. Folic acid dispensation rates in both age groups were designated as fixed effects variables, and year and region constituted random effects.

RESULTS: Population-adjusted median regional prescription rates of folic acid for 20-24-year-olds during 2006-2021 varied over the national median by factor 0.55-1.73 and 0.47-2.00 in females and males, respectively. Regional yearly folic acid prescription rates in 20-24-year-old males were positively associated with male ESM (β=0.376, p=0.0104), whereas prescription rates in 25-29-year-old males were independently and inversely associated with male ESM (β=-0.456, p=0.0017). These associations remained significant after accounting for the interaction term between folic acid dispensation rates in the two age groups. No association was demonstrated in females (p>0.1).

CONCLUSION: Regional folic acid dispensation rates were positively associated with ESM in males aged 20-24, while an inverse association was observed in those aged 25-29. These findings did not replicate previously reported suicide-protective effects of folic acid, potentially suggesting confounding by indication.

References

  1. Asbaghi O, Ashtary-Larky D, Bagheri R, Moosavian SP, Nazarian B, Afrisham R, et al. Effects of Folic Acid Supplementation on Inflammatory Markers: A Grade-Assessed Systematic Review and Dose–Response Meta-Analysis of Randomized Controlled Trials. Nutrients. 2021 Jul 6;13(7):2327.
  2. Batty GD, Bell S, Stamatakis E, Kivimäki M. Association of Systemic Inflammation With Risk of Completed Suicide in the General Population. JAMA Psychiatry. 2016 Sep 1;73(9):993. doi:10.1001/jamapsychiatry.2016.1805
  3. Kim JM, Kim HY, Lee HJ, Kim JW, Kang HJ, Kim SW, et al. Prediction of Suicidality According to Serum Folate Levels in Depressive Patients Receiving Stepwise Pharmacotherapy. Front Psychiatry. 2021 Dec 2;12:747228.
  4. Feng L, Li S, Li C. Association between folate intake and suicidal ideation: NHANES 2005–2018 and Mendelian randomization. Journal of Affective Disorders. 2025 Nov;389:119730.
  5. Gibbons RD, Hur K, Lavigne JE, Mann JJ. Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults. JAMA Psychiatry. 2022 Nov 1;79(11):1118. doi:10.1001/jamapsychiatry.2022.2990