Schizophr Res. 2026 Oct 17;298:205-213. doi: 10.1016/j.schres.2026.10.009. Online ahead of print.

ABSTRACT

BACKGROUND: A well-established connection exists between psychoses and depression, with one presentation being depressive symptoms before psychosis. However, the predictive power of preceding affective symptoms is reported to be low, raising the question whether depressive symptoms could reflect intermediary phenotypes associated with high polygenic risk for schizophrenia (PRSscz). We examined whether PRSscz is associated with depressive symptoms from adolescence to middle age in those who did not develop a non-affective psychosis.

METHODS: We used the population-based Young Finns Study (n = 2291). Depressive symptoms were measured with the Beck Depression Inventory-II and its modified version (suitable for non-clinical symptoms) between ages 15 and 56. Covariates included age, sex, childhood family environment, and adulthood education and income. The Care Register for Health Care was used to exclude participants with non-affective psychoses until middle age.

RESULTS: High PRSscz was associated with higher performance difficulties from adolescence to early adulthood and higher depressive cognitions when approaching middle age. These associations were sustained in the fully adjusted models. PRSscz did not show consistent associations with the total amount of depressive symptoms or somatic/affective symptoms.

CONCLUSIONS: First, PRSscz appears to explain age-specific fluctuations in depressive symptoms. Second, PRSscz may not predict the full symptom profile of major depression (i.e., it was not associated with affective/somatic symptoms). Third, high PRSscz explains depressive symptoms during periods typical for prodromal syndromes, even among those who do not develop psychosis. Thus, depressive symptoms in adolescence may represent intermediary phenotypes or transdiagnostic susceptibilities related to high PRSscz.

PMID:42892069 | DOI:10.1016/j.schres.2026.10.009