I mentioned before that in psychiatry, we don't have many lab tests. In a standard work-up I might check none, or just a few. If a new patient has seen his primary care doctor within a reasonable amount of time, I might check the thyroid, B12, and folate and be done with it. I used to check vitamin D on everyone, but everyone was low, so now I tell patients to supplement with 2000 IU a day and then I check it (plus calcium) after 3 months.
Why B12 (available from animal foods) and folate? Both are B vitamins involved in nerve health and the formation of the all-important neurotransmitters. B12 deficiency can definitely cause depression along with other nerve damage over time (1)(2). In many years of doing this testing, I've caught several underactive thyroids, a few B12 deficiencies, but no folate deficiencies. Not one. In America, all grain-based food is supplemented with folate. Maybe that's why.
I've never tested for B6. It just wasn't a test we were taught to do, or to look out for. B12 deficiency is pretty common (6% of adults) - we have variable abilities to absorb it from our guts, and some people will need shots in order to keep from being low. B6 deficiency - hadn't even thought about it, really. But it stands to reason that we might need it to keep from being depressed. Recall that the all-important serotonin is made from the amino acid tryptophan. Along the way, we need B6 (and zinc) to help the process. B6 is also required to make other neurotransmitters, dopamine and norepinephrine (see this diagram from the archives of EvMedForum).
Which brings me to this study from June's American Journal of Clinical Nutrition - "Longitudinal association of vitamin B6, folate, and vitamin B12 with depressive symptoms among older adults over time."
Basically, a group in Chicago followed a mixed-race group of older adults for an average of 7 years. Food questionnaires and a 10-item Center for Epidemiologic Studies Depression Scale were administered every three years in about 3500 people aged 65 or older.
Let's stop and take a deep breath for a moment. Because, come on. A food questionnaire every three years? A 10 item scale for depression I've never even heard of, and I'm a psychiatrist? Compare the methods in this study to the Heart and Soul study, another large observational trial. In Heart and Soul, they did a real clinical research diagnostic interview - the gold standard, and they drew blood to get actual lab measures. This study is 3 times as big and maybe that's why they used cheap, crappy measures, but you hardly even know what the data is worth at the end. Two pages of this study describe how they managed to squeeze some so-called information out of it - they used "logistic regression with the generalized estimating equation to model the likelihood over time of a participant becoming depressed," plus some logit link functions, and binomial error structure. I'm sure those are all very sensible things for a statistician to do, but wouldn't it have been better to use a bigger, better scale in the first place? Sigh.
We don't have that many nutritional studies in psychiatry. I feel like I need to look at all of them, even the lousy ones. And this one was published in the premier nutrition journal! (Along with that crazy meat makes you fat study).
Anyway! Somehow, from those once-every-three-year food questionnaires, they figured out which older adults were deficient in B6, folate, and B12. They controlled for things like age, smoking, alcohol, sex, race, education, etc. In the end, high total (food + supplement) intake of B12 and B6 were associated with a decreased likelihood of the development of depression over the study period of 7.2 years. Folate intake didn't seem to have any impact, and the B6 difference was primarily made in the supplementing group. Meaning people with the education and wherewithal to take a multivitamin. Which could be a huge confounder. At least the editorial in the same issue admits that more studies need to be done. And done well.