The Corpus Callosum

Context  Depression has incidentally been related to altered levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), but this relation has never been studied systematically.

Objective  To determine in a large population-based cohort whether there is an association between depression and altered 25(OH)D and PTH levels...

Main Outcome Measure  Depression was measured using self-reports (Center for Epidemiologic Studies-Depression scale) and diagnostic interviews (Diagnostic Interview Schedule). Levels of 25(OH)D and PTH were assessed. Potentially confounding factors (ie, age, sex, smoking status, body mass index, number of chronic conditions, and serum creatinine concentration) and explanatory factors (ie, season of data acquisition, level of urbanization, and physical activity) were also measured.

Results  Levels of 25(OH)D were 14% lower in 169 persons with minor depression and 14% lower in 26 persons with major depressive disorder compared with levels in 1087 control individuals (P < .001). Levels of PTH were 5% and 33% higher, respectively (P = .003). Depression severity (Center for Epidemiologic Studies Depression Scale) was significantly associated with decreased serum 25(OH)D levels (P = .03) and increased serum PTH levels (P = .008).

Conclusion  The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH)D levels and increased serum PTH levels in older individuals.

Of course finding a correlation does not say anything about causation.  Even if it did say something about causation, it would not necessarily imply anything about treatment.  Young points out that most research on the potential antidepressant effect of Vitamin D supplementation is not very helpful.  He cites two studies that had adequate design, but both used subjective feelings of positive affect or well-being as outcome measures.  That is nice, but not informative with regard to treatment of clinically significant depression.

He mentions a few other theoretical considerations, then concludes:

Treatment of depression with vitamin D is an idea worth testing in carefully selected populations. This includes those with low vitamin D levels, especially the elderly, who have an increased incidence of low vitamin D, and patients with seasonal affective disorder who do not respond to light therapy. If there are patients in whom vitamin D is an effective antidepressant, this is likely to be one of the most costeffective treatments in psychiatry, and one with negligible side effects.

Note that he specifically is not arguing that vitamin D supplementation should be considered as anywhere near clinically validated for treatment.  Rather, he is suggesting that it might be worth pursuing in limited settings.

Also note that JPN is a Canadian journal.  As Razib pointed out a while ago, vitamin D deficiency is common among non-white persons in Canada.  Perhaps that is where some of the interest comes from.  The authors of the Arch Gen Psychiatry article are from the Netherlands, another high-latitude country. 

Dr. Young  points out that the best evidence regarding mood effects of vitamin D shows only that it perks some people up a bit.  So how does he use that as a basis to say that he ought to study it more? 

Well, I can't speak for him, but since this is my blog, I happily will speak for myself.  First, I would be skeptical of the notion that vitamin D will be found to be an "effective antidepressant" in the usual sense.  That is, if it were given as a sole treatment in a randomized double-blind clinical trial, compared with placebo and and active comparator, I doubt it would be very impressive.  You never know until you try, but I still doubt it. 

However, that does not mean we should forget it.  Not at all.  Even if all it does is to perk people up a little bit, it still could be a useful part of our armamentarium.  The reason is this: in the treatment of depression, with antidepressants, it is common for people to show significant improvement, while not attaining full remission.  For example, let's say you have a moderately severe depression, with a BDI score of 28.  You start of sertraline, get up to a dose of 200mg for six weeks.  You get 50% better.  Your BDI is now 14.  You can function OK, but there are problems.  For one, you are not at your best, probably still fairly unhappy, fairly often.  Two, you are running a higher risk of relapse back into a full episode. 

In such a situation, there are many things you could do, and it is likely that you eventually would find some intervention to get that score down to 7 or so, which would be a remission.

But, there are some people who go through a lengthy course of interventions, often two or three at a time, but never quite get there.  The way I see it, you might get a 50% improvement with the medication.  Then maybe you have the energy to start regular exercise, and you get another 5%.  You start eating better, and get another 5%.  You join a volunteer group, get another 5%.  And so forth.  Some people need a lot of those 5% increments of improvement.  I suspect that our medical-industrial complex discards a lot of things that are like that: a little bit helpful, but with no potential to be a blockbuster.

The FDA will never approve something that results in only a 5% improvement.  Especially if it can't be patented.  But those little things can be important.  In selected populations, perhaps vitamin D would give a boost of a lot more than 5%.  I'm particularly curious about the people who don't respond to bright light treatment.  The lights used for this treatment are filtered so the patient is not exposed to ultraviolet light.  We think that is good, but maybe it reduces the effect for some people.