Acta Psychiatr Scand 2017: 1 All rights reserved DOI: 10.1111/acps.12798
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA PSYCHIATRICA SCANDINAVICA
Letter to the editor
Comment on Vitamin D serum levels are cross-sectionally but not prospectively associated with late-life depression To the Editor, Vitamin D deficiency is widely prevalent in the general population and is even more prevalent among those with major depressive disorder. This finding has generated considerable interest in whether vitamin D deficiency may have a causative role in depression and whether vitamin D replenishment may have a therapeutic role in major depressive disorder (1, 2). Recently, Jovanova et al. (1) attempted to ascertain whether vitamin D deficiency plays a causative role in depression by determining whether vitamin D levels are prospectively associated with later changes in measures of depression. They hypothesized that if vitamin D deficiency plays a causative role in depression, those with deficiency would have a differential risk for or course of depression compared to those with higher levels of vitamin D. Consistent with the literature, they found a cross-sectional association between vitamin D deficiency and depression. They failed to find a prospective association between vitamin D and later measures of depression and concluded that vitamin D deficiency is more likely to be secondary to depression or secondary to residual confounding than a factor contributing to depression. Based on those results, McGrath expressed skepticism that randomized controlled trials would show efficacy for vitamin D in the treatment of depression (2). The conclusions drawn by Jovanova et al. and McGrath are not fully supported by the data reported (1, 2). Jovanova et al. only reported vitamin D levels from the beginning of the study period. They do not report any data as to how patients were treated, either for depression or for vitamin D deficiency, or whether those who were not deficient at the outset of the trial went on to develop deficiency later (1). These points are particularly important given that if vitamin D is found to be an effective primary or adjunctive treatment for depression in individuals with vitamin D deficiency, then worse outcomes predicted for the vitamin D deficiency group might have been offset by treatment of the deficiency (either through supplementation or encouragement to increase sun exposure) in the patients being studied. The authors do point out the limitation that vitamin D levels were only measured at baseline, but they fail to address how treatment or even patient knowledge of deficiency might have affected their results. Further, as crosssectional vitamin D deficiency was associated with increased depressive scores at baseline, it may have been associated with increased antidepressant treatment that may have prevented later instances of depression or worse outcomes. McGrath (2) rightly points out that randomized controlled trials are needed to definitively determine a role for vitamin D in treating depression. Several randomized controlled trials have been published. While results have been generally negative in vitamin D treatment/prevention studies that do not use
vitamin D deficiency as inclusion criteria or use biologically flawed methodology, randomized controlled trials of vitamin D augmentation of antidepressant therapy in individuals with vitamin D deficiency have shown promising results (3). Randomized controlled trials performed subsequent to up-to-date meta-analyses have shown good results in comorbid vitamin D deficiency and premenstrual syndrome-related mood disorders (4) and a promising trend in a low n trial in comorbid vitamin D deficiency and major depressive disorder (5). Considering these results and the methodical limitations of the study by Jovanova et al., the hypotheses that vitamin D deficiency is one factor with a causative role in depressive disorders and that vitamin D deficiency impairs recovery from depressive disorders both remain valid. As Jovanova et al. (1) rightly point out, whether vitamin D levels affect the course of depression or not, those with depression are more likely to have vitamin D deficiency, and therefore, individuals with depression comprise an at-risk group. Even if biologically well-designed, randomized, and controlled trials fail to show benefit for vitamin D in the treatment of depression in deficient individuals, replenishment may be indicated for bone health. T. C. Griffen X Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA E-mail: trevor.griff[email protected]
References 1. Jovanova O, Aarts N, Noord R, Carola-Zillikens M, Hofman A, Tiemeier H. Vitamin D serum levels are crosssectionally but not prospectively associated with late-life depression. Acta Psychiatr Scand 2017;135:185–194. 2. McGrath JJ. Vitamin D and mental health – the scrutiny of science delivers a sober message. Acta Psychiatr Scand 2017;135:183–184. 3. Spending S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients 2014;6:1501–1518. 4. Tartagni M, Cicinelli MV, Tartagni MV et al. Vitamin D supplementation for premenstrual syndrome-related mood disorders in adolescents with severe hypovitaminosis D. J Petiatr Adolesc Gynecol 2016;29:357–361. 5. Sepehrmanesh Z, Kolahdooz F, Abedi F et al. Vitamin D supplementation affects the beck depression inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: a randomized, controlled clinical trial. J Nutr 2016;146:243–248.
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© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA PSYCHIATRICA SCANDINAVICA
Letter to the editor
Comment on Vitamin D serum levels are cross-sectionally but not prospectively associated with late-life depression To the Editor, Vitamin D deficiency is widely prevalent in the general population and is even more prevalent among those with major depressive disorder. This finding has generated considerable interest in whether vitamin D deficiency may have a causative role in depression and whether vitamin D replenishment may have a therapeutic role in major depressive disorder (1, 2). Recently, Jovanova et al. (1) attempted to ascertain whether vitamin D deficiency plays a causative role in depression by determining whether vitamin D levels are prospectively associated with later changes in measures of depression. They hypothesized that if vitamin D deficiency plays a causative role in depression, those with deficiency would have a differential risk for or course of depression compared to those with higher levels of vitamin D. Consistent with the literature, they found a cross-sectional association between vitamin D deficiency and depression. They failed to find a prospective association between vitamin D and later measures of depression and concluded that vitamin D deficiency is more likely to be secondary to depression or secondary to residual confounding than a factor contributing to depression. Based on those results, McGrath expressed skepticism that randomized controlled trials would show efficacy for vitamin D in the treatment of depression (2). The conclusions drawn by Jovanova et al. and McGrath are not fully supported by the data reported (1, 2). Jovanova et al. only reported vitamin D levels from the beginning of the study period. They do not report any data as to how patients were treated, either for depression or for vitamin D deficiency, or whether those who were not deficient at the outset of the trial went on to develop deficiency later (1). These points are particularly important given that if vitamin D is found to be an effective primary or adjunctive treatment for depression in individuals with vitamin D deficiency, then worse outcomes predicted for the vitamin D deficiency group might have been offset by treatment of the deficiency (either through supplementation or encouragement to increase sun exposure) in the patients being studied. The authors do point out the limitation that vitamin D levels were only measured at baseline, but they fail to address how treatment or even patient knowledge of deficiency might have affected their results. Further, as crosssectional vitamin D deficiency was associated with increased depressive scores at baseline, it may have been associated with increased antidepressant treatment that may have prevented later instances of depression or worse outcomes. McGrath (2) rightly points out that randomized controlled trials are needed to definitively determine a role for vitamin D in treating depression. Several randomized controlled trials have been published. While results have been generally negative in vitamin D treatment/prevention studies that do not use
vitamin D deficiency as inclusion criteria or use biologically flawed methodology, randomized controlled trials of vitamin D augmentation of antidepressant therapy in individuals with vitamin D deficiency have shown promising results (3). Randomized controlled trials performed subsequent to up-to-date meta-analyses have shown good results in comorbid vitamin D deficiency and premenstrual syndrome-related mood disorders (4) and a promising trend in a low n trial in comorbid vitamin D deficiency and major depressive disorder (5). Considering these results and the methodical limitations of the study by Jovanova et al., the hypotheses that vitamin D deficiency is one factor with a causative role in depressive disorders and that vitamin D deficiency impairs recovery from depressive disorders both remain valid. As Jovanova et al. (1) rightly point out, whether vitamin D levels affect the course of depression or not, those with depression are more likely to have vitamin D deficiency, and therefore, individuals with depression comprise an at-risk group. Even if biologically well-designed, randomized, and controlled trials fail to show benefit for vitamin D in the treatment of depression in deficient individuals, replenishment may be indicated for bone health. T. C. Griffen X Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA E-mail: trevor.griff[email protected]
References 1. Jovanova O, Aarts N, Noord R, Carola-Zillikens M, Hofman A, Tiemeier H. Vitamin D serum levels are crosssectionally but not prospectively associated with late-life depression. Acta Psychiatr Scand 2017;135:185–194. 2. McGrath JJ. Vitamin D and mental health – the scrutiny of science delivers a sober message. Acta Psychiatr Scand 2017;135:183–184. 3. Spending S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients 2014;6:1501–1518. 4. Tartagni M, Cicinelli MV, Tartagni MV et al. Vitamin D supplementation for premenstrual syndrome-related mood disorders in adolescents with severe hypovitaminosis D. J Petiatr Adolesc Gynecol 2016;29:357–361. 5. Sepehrmanesh Z, Kolahdooz F, Abedi F et al. Vitamin D supplementation affects the beck depression inventory, insulin resistance, and biomarkers of oxidative stress in patients with major depressive disorder: a randomized, controlled clinical trial. J Nutr 2016;146:243–248.
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