Age of onset of major depressive episode and association with lifetime psychiatric disorders, health-related quality of life and impact of gender: A cross sectional and retrospective cohort study.

OBJECTIVE: To assess the long-term impact of the age of onset (AOO) of the first major depressive episode (MDE) according to 3 age groups and considering gender. METHODS: Data were extracted from NESARC III, a representative U.S. SAMPLE: We included 8053 participants with an MDE history in a cross-sectional and retrospective cohort study. We defined 3 AOO groups: childhood-onset (< 13 yo), adolescence-onset (13-18 yo), and adult-onset (> 18 yo). We compared sociodemographic characteristics, lifetime psychiatric disorders per DSM-5 criteria, and health-related quality of life (HRQOL) in each group and performed gender-stratified analyses. RESULTS: Prevalence of childhood-onset MDE was 10.03 %, adolescence-onset was 14.12 %, and adult-onset was 75.85 %. Suicide attempts (AOR = 3.61; 95 % CI 2.90-4.50), anxiety disorders (AOR = 1.92; 95 % CI 1.62-2.27), and personality disorders (AOR = 3.08; 95 % CI 2.56-3.71) were more frequent in the childhood-onset than in the adult-onset one. Adolescence-onset group showed similar results. Physical Disability scale (p < 0.001) and Mental Disability scale (p < 0.001) were significantly lower in the childhood-onset group. Results were more nuanced in the adolescence-onset group. Women in childhood-onset and adolescence-onset groups had poorer outcomes than the adult-onset group. Differences were less pronounced in men. LIMITATIONS: Recall and classification biases inherent to survey design. CONCLUSION: Individuals, particularly women, who experienced their first MDE during childhood or adolescence exhibit higher lifetime psychiatric disorder prevalence and poorer HRQOL than those with adult-onset MDE. These findings highlight the importance of preventive measures, early diagnosis, and treatment of youth depression.

Divergent local and systemic antitumor response in primary uveal melanomas.

Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage.