2026 ECNP Congress

EP01-1061

Vitamin D levels and suicidality in patients with major depressive disorder: a systematic review and meta-analysis

Anastasios Stefanou — E. Vlachou, T. Karagiannis, V.P. Bozikas, A. Agorastos · Aristotle University of Thessaloniki, 2nd Department of Psychiatry - School of Medicine, Thessaloniki, Greece

2026 ECNP Congress

Background: Suicidality is the most severe complication of depression, though increasingly conceptualized as transdiagnostic. Both Major Depressive Disorder (MDD) and suicidality have independently been associated with reduced vitamin D levels in the peripheral blood [1,2]. Vitamin D is involved in neurobiological processes relevant to mood regulation, including neuroimmune and neuroendocrine pathways [3]. However, it remains unclear whether serum vitamin D levels are associated with suicidality within individuals with MDD. The aim of this systematic review and meta-analysis was to examine differences in these levels between patients with MDD with and without suicidality.

Methods: We systematically searched MEDLINE, Web of Science and APA PsycINFO up to April 2026, for observational studies (cross-sectional, case-control, prospective or retrospective cohort designs) reporting serum vitamin D levels in individuals with MDD, grouped according to presence or absence of suicidality (i.e. suicidal thoughts and/or behaviours). A meta-analysis was conducted comparing vitamin D levels between groups, with the use of a random-effects model. The effect size applied was the weighted mean difference (MD) along with the 95% confidence intervals (CI). Heterogeneity was assessed by visual inspection of forest-plots and quantified using I2-statistic. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS), with a modified version applied for cross-sectional studies [4]. Subgroup analysis by country of study explored heterogeneity. To assess robustness of our results, sensitivity analyses were performed excluding studies with low methodological quality (NOS score lower than 8). To account for seasonal variations of vitamin D, we planned a meta-regression according to percentage of summertime measurements.

Results: Our systematic review included three observational studies, each conducted in the USA, Sweden and India respectively. We included a total of 225 participants, diagnosed with MDD. Of these,102 participants presented with suicidal ideation or suicidal behaviors. All included studies had a NOS score of at least 8, indicative of high methodological quality. The meta-analysis showed significantly lower vitamin D levels in patients with MDD and suicidality compared to those without suicidality (MD=-12.53nmol/l, 95% CI:-21,65; -3.40, p-value<0.01, I2=40.8%). Analysis by country showed no difference between subgroups, though the limited number of studies hindered meaningful subgroup comparisons. Meta-regression was not conducted as only three studies were included.

Conclusion: Our meta-analysis indicates an inverse association between vitamin D levels and suicidality, even within the context of depression. While the cross-sectional design and limited number of included studies warrant caution, this finding suggests that vitamin D may be associated with suicidal phenotypes within MDD. From a translational perspective, vitamin D may represent a peripheral marker, though the limited studies and absence of interventional evidence of vitamin D supplementation on suicidal outcomes mitigate clinical utility. However, these findings may support future research exploring vitamin D within broader mechanistic frameworks of within-MDD suicidality, potentially contributing to precision-psychiatry approaches of the stratification of the suicidal risk in such populations.

References

  1. Ju SY, Lee YJ, Jeong SN. Serum 25-hydroxyvitamin D levels and the risk of depression: a systematic review and meta-analysis. J Nutr Health Aging. 2013;17(5):447–55. doi:10.1007/s12603-012-0418-0 PubMed PMID: 23636546; PubMed Central PMCID: PMC12878238.
  2. Yu J, Mohammad SN, Khachatryan LG, Mohammed JS, Menon SV, Kaur M, et al. Risk of suicide, suicide attempt, and suicidal ideation among people with vitamin D deficiency: a systematic review and meta-analysis. BMC Psychiatry. 2025 Feb 26;25(1):177. doi:10.1186/s12888-025-06613-w PubMed PMID: 40000977; PubMed Central PMCID: PMC11863558.
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  4. Herzog R, Álvarez-Pasquin MJ, Díaz C, Del Barrio JL, Estrada JM, Gil Á. Are healthcare workers’ intentions to vaccinate related to their knowledge, beliefs and attitudes? a systematic review. BMC Public Health. 2013 Feb 19;13:154. doi:10.1186/1471-2458-13-154 PubMed PMID: 23421987; PubMed Central PMCID: PMC3602084.