Childhood trauma combined with suicide attempts affects cognitive function and inflammation levels in drug-naive patients with major depressive disorder

Psychoneuroendocrinology. 2025 Sep 16;182:107611. doi: 10.1016/j.psyneuen.2025.107611. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood trauma (CT) and suicide attempts (SA) independently associate with cognitive impairment in major depressive disorder (MDD), but their interactive effect and biology mechanisms still unknown.

METHODS: We recruited a total of 156 first-episode drug-naïve patients with MDD and 90 healthy controls (HC). Using the Childhood Trauma Questionnaire (CTQ), Beck Scale for Suicide Ideation-Chinese Version (BSI-CV), and Repeatable Battery for Assessment of Neuropsychological Status (RBANS) to assess recruited patients with MDD and HC. And we measured the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor-2 (TNFR2), catalase (CAT), glutathione reductase (GSR) and superoxide dismutase (SOD) in MDD patients using enzyme-linked immunosorbent assay (ELISA).

RESULTS: MDD patients demonstrated significantly lower scores across all cognitive domains compared to HC (p < 0.001). In MDD patients, a significant interaction between CT and SA history was observed for RBANS total scores (p = 0.028), immediate memory (p = 0.045), attention (p = 0.008), and TNF-α levels (p = 0.018), while CT independently affected GSR levels (p = 0.034). Stratifying MDD patients into four subgroups (CT⁺SA⁺, CT^–SA⁺, CT⁺SA^–, CT^–SA^–) revealed that the CT⁺SA⁺ group had significantly lower RBANS total scores (p = 0.01) and attention scores (p < 0.001) than other subgroups. TNF-α levels showed no significant differences among four subgroups (p = 0.047).

CONCLUSION: CT and SA may synergistically exacerbate cognitive impairment, especially attention deficit, in drug-naive patients with MDD and may tend to increase TNF-α levels.

PMID:41016322 | DOI:10.1016/j.psyneuen.2025.107611