Inflammation in older subjects with early- and late-onset depression in the NESDO study: a cross-sectional and longitudinal case-only design.

OBJECTIVE: Different biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression. METHODS: The study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1ß, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined. RESULTS: After adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05-1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression. CONCLUSIONS: This study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression.

Further evidence for an association of HLA-DR7 with basal cell carcinoma on the tropical island of Saba.

OBJECTIVE: To establish the association of HLA alleles (ie, HLA-DR1, HLA-DR4, and HLA-DR7) with individuals with skin cancer on the tropical island of Saba. This island was chosen because most of the white population has fair skin and excessive exposure to sunlight, which results in a high prevalence of skin cancer. DESIGN: HLA typing was performed in 124 white individuals with histologically proven basal cell and/or squamous cell carcinoma and in control subjects. Skin type, the presence of freckling, and the number of actinic keratoses were determined. SETTING: Population-based study. SUBJECTS: Inhabitants of Saba with and without skin cancer. MAIN OUTCOME MEASURE: Presence of HLA-DR1, HLA-DR4, and HLA-DR7 alleles. RESULTS: Associations of HLA alleles with basal cell and squamous cell carcinoma have been reported. The presence of the HLA-DR7 allele was positively associated with the development of basal cell carcinoma (odds ratio, 3.8; 95% confidence interval, 1.1-13.4). Adjustment for skin type, which is a potentially confounding factor for the association between HLA alleles and skin cancer, did not substantially alter this association. No other associations between HLA alleles and skin cancer were found, possibly because of the small size of the study population. CONCLUSION: This study presented further evidence for an association between HLA-DR7 and basal cell carcinoma. Arch Dermatol. 2000;136:1019-1022