Although the data do not specifically address causation of suicidal ideation, a study published in Psychiatry Research found that patients with major depressive disorder (MDD) and suicidal ideation had lower levels of serum brain-derived neurotrophic factor (BDNF) than patients with MDD and no suicidal ideation, but without significant increases in depression severity.

Studies on the neurotrophic hypothesis of depression have had mixed results, although there is evidence that low BDNF levels can be linked to suicidality, if not MDD specifically. The current study assessed the levels of serum BDNF in 68 physically healthy individuals with MDD who had been unmedicated for at least 6 weeks prior and 76 healthy controls. Participants were divided into 3 groups: no suicidal ideation (n=40), suicidal ideation without being actively suicidal (n=28), and healthy controls (n=76). The total Hamilton Depression Rating Scale (HDRS-17) was used to measure past-week depression severity, with suicide item number 3 serving as a rating for suicidal ideation.

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When all MDD subjects combined were compared with healthy controls, small differences in BDNF levels were seen (df=141, P =.292), although post-hoc analysis showed significant differences only between MDD-suicide ideation and MDD-no suicide ideation (P =.038). Levels of serum BDNF were significantly lower in suicide ideation participants compared with no suicide ideation participants, with a moderate 2-group comparison effect size (n=40; t=2.468, P =.016, d=0.622). The group difference remained significant after investigators controlled for potential confounders (sex, age, body mass index, perceived stress scale, smoking, platelet count, and Yale Physical Activity Survey; df=1, F=4.442, P <.05). When the suicide item was excluded from the total score, the no suicide ideation and suicide ideation groups did not show significantly different total HDRS-17 scores (P =.465). Levels of serum BDNF were not significantly associated with depression severity (total HDRS-17 score; df=1, β=−0.098, P =.424) or any subscales of the HDRS-17 that were assessed as exploratory independent variables.

Study investigators concluded, “While some studies have examined BDNF levels in suicidal attempts and completion, our assessment of [suicide ideation] and its relationship to BDNF levels provides some insight into the neurobiology of depression and suicidality and should be further explored to understand the mechanisms by which [suicide ideation] develops, although our data do not specifically address causal relationships.”


Khan MS, Wu GWY, Reus VI, et al. Low serum brain-derived neurotrophic factor is associated with suicidal ideation in major depressive disorder [published online January 3, 2019]. Psychiatry Res. doi: 10.1016/j.psychres.2019.01.013