Neurocognition, childhood trauma and suicidal ideation in drug-naïve first-episode major depressive disorder: a comparison of younger- versus older-onset patients

Age‑at‑onset is an important dimension for subtyping major depressive disorder (MDD). Few studies have jointly compared childhood trauma, suicidal ideation and cognition performance between drug-naïve first-episode adult MDD patients with younger-onset versus older-onset. This study explored their clinical and cognitive differences and cognitive correlates. A total of 349 first-episode, drug-naïve MDD patients (younger‑onset: age of onset < 30 years; older‑onset: age of onset ≥ 30 years) and 287 healthy controls (HCs) from a Chinese multicenter cohort were enrolled. All MDD patients finished the Childhood Trauma Questionnaire-Short Form (CTQ-SF), Mini-International Neuropsychiatric Interview (MINI), 17-item Hamilton Depression Rating Scale (HAMD-17) and five-domain cognitive tests. HCs completed the CTQ and cognitive assessments. MANCOVA, correlation and multiple linear regression analyses were performed. Both MDD subgroups exhibited higher CTQ-SF scores than HCs, with similar suicidal ideation rates. Younger-onset MDD showed impairments across all five cognitive domains, while older-onset MDD exhibited deficits only in processing speed, verbal learning and executive function. Younger-onset patients performed worse than older-onset MDD patients in processing speed and Hopkins Verbal Learning Test‑Revised (HVLT-R) learning. Younger age-at-onset and male sex predicted poorer processing speed and executive function, while the presence of suicidal ideation was associated with better processing speed. Total CTQ-SF and HAMD-17 scores could not predict cognition. Exploratory cognitive patterns associated with age‑at‑onset were observed among untreated first-episode adult MDD. Onset age may serve as a clinically relevant marker for cognitive heterogeneity in newly‑diagnosed MDD. ClinicalTrials.gov identifier: NCT02023567; registration date: 15 December 2013.