Antidepressants differentially related to 1,25-(OH)2 vitamin D3 and 25-(OH) vitamin D3 in late-life depression

A low plasma 25-OH vitamin D-3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)(2) vitamin D-3, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D-3, 1,25-(OH)(2) vitamin D-3 and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age >= 60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D-33 (Cohen's d = 0.28 (95% confidence interval: 0.07-0.49), P = 0.033) as well as 1,25-(OH)(2) vitamin D3 (Cohen's d = 0.48 (95% confidence interval: 0.27-0.70), P < 0.001) than comparison subjects. Of all depression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)(2) vitamin D-3 levels (Cohen's d = 0.86 (95% confidence interval: 0.53-1.19), P < 0.001), but not its often measured precursor 25-OH vitamin D-3. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D-3 and 1,25-(OH)(2) vitamin D-3 levels suggests modulation of 1-a-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression.