Impact of age at onset on the phenomenology of depression in treatment-seeking adults in the STARD trial

•Age at onset is an important factor in describing depressive episodes in adults.•Early age at onset is associated with greater depression symptom severity.•Adolescent-onset symptom networks displayed unique connectivity patterns.•Adolescent-onset symptom networks were most densely connected. — Adolescence is characterized by biological, emotional, and behavioral changes. The onset of depression during this vulnerable time may confer specific risks. This study examined whether symptoms of depression were associated with age at onset (AAO), and whether AAO impacted depression symptom networks in adulthood. — Data were from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. 3,184 depressed participants were included in analyses. A series of multiple regressions examined whether pretreatment differences in depression item-level symptom severity varied by AAO. Participants were divided into four groups based on AAO; GLASSO networks of depressive symptoms were estimated in each group and tests of differences between networks were performed. — Earlier AAO was associated with more severe symptom levels, with the exception of sleep—which increased with AAO, and loss of libido, psychomotor disturbance, and appetite-weight disturbance, which were invariant with AAO. In network analyses, the adolescent AAO symptom network significantly differed from the young adult and middle age AAO networks in structure and strength. In contrast, the child AAO network differed from the middle age AAO network in strength only. — Age at onset was recalled retrospectively and may be subject to bias. Future prospective studies should be conducted to address this limitation. — Adolescence stands out as a time when onset of depression is associated with specific network characteristics. The unique severity of symptoms and network strength and structure caused by onset of depression during adolescence highlights the long-lasting impact of depression on the developing brain.