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Tryptophan, Tyrosine May Battle Early Postpartum Depression

Major Finding: Scans revealed 43% more monamine oxidase across all brain regions in women during postpartum days 4-6, compared with those in controls.

Data Source: A case-control study of 15 postpartum women and 15 matched controls at a tertiary care academic psychiatric hospital.

Disclosures: The initial study was funded by the Canadian institutes of Health Research and other national Canadian health alliances. Dr. Meyer said he has no financial conflicts.


 

FROM THE WORLD CONFERENCE ON WOMEN'S MENTAL HEALTH

MADRID – Beefing up a pregnant woman’s diet with tryptophan and tyrosine might one day help avoid the "baby blues" – or even a downward slide into postpartum depression.

The proteins – found naturally in eggs, poultry, milk products, and some nuts and seeds – are important precursors of the mood-regulating brain monoamines dopamine, serotonin, and norepinephrine. Boosting them before giving birth could provide just enough cushion to counteract the effects of increased monoamine oxidase A (MAO-A). MAO-A rises sharply in the week after childbirth, metabolizing these neurotransmitters at a highly increased rate, which probably plays a key role in the emotional dysregulation many women experience, Dr. Jeffrey Meyer said March 17 at the World Conference on Women’s Mental Health .

"What we are emphasizing now in our research is trying to compensate for this increased MAO-A metabolism of serotonin, norepinephrine, and dopamine," he said. "Giving these precursor proteins might be a potential strategy to lower the intensity of the postpartum ‘blues’ and possibly lead to a treatment for postpartum depression."

Recent work in humans shows that MAO-A in postpartum women is inversely related to estrogen. This relationship, in which estrogen declines as MAO-A rises, could underlie the feelings of sadness that affect up to 75% of women around postpartum days 3-6, said Dr. Meyer, an associate professor in the psychiatry department at the University of Toronto.

Since he and his colleagues published their initial work on the MAO-A/estrogen connection last May (Arch. Gen. Psychiatry 2010;67:468-74), Dr. Meyer has begun to investigate whether nutritional supplementation with the precursor proteins could boost a woman’s mood-regulating neurotransmitters enough to ward off the enzyme’s postpartum effects.

The first step of that research is to examine how tyrosine and tryptophan – the proteins under investigation – affect breast milk. "If we see that there is a negligible level in milk relative to plasma, our next step will be to investigate whether their administration could attenuate postpartum blues," he said.

The ultimate goal, however, would not be yet another prenatal supplement. "Ideally, instead of giving a powder as we’re doing now [during research], we could offer some specific dietary recommendations – maybe recommending that a pregnant woman should have a diet rich in tryptophan and tyrosine."

Such an intervention would probably be more acceptable than a medication, because it would circumvent concerns about drug excretion into breast milk, he added.

Dr. Meyer’s research is based on previous animal studies – including his own – that show a precipitous drop in plasma estrogen within 48 hours of birth. Almost simultaneously and nearly in concert, Dr. Meyer said, MAO-A levels begin to rise. Plasma estrogen reaches its nadir around day 3, while MAO-A peaks around day 4. "Coincidentally, this is the typical time of postpartum sadness– this period of low mood, irritability, and sleeplessness," Dr. Meyer said. He also said that his work represents the only MAO-A/estrogen investigation in humans.

That study looked at 15 immediately postpartum women and 15 age-matched controls, all of whom underwent positron emission tomography with the radiotracer carbon 11–labeled harmine. The compound is extremely reliable for identifying brain levels of MAO-A, and has a 20-minute half-life, making it a good choice for lactating women, he noted. To further allay safety concerns, breast feeding was delayed for 12 half-lives of the radiotracer, with a test sample confirming that the milk was clear. Geiger counters placed on the mothers’ chests also ensured that background radiation was normal.

The new mothers all were scanned on postpartum days 4-6 – the most common time for symptoms of postpartum sadness to appear. The scans revealed 43% more MAO-A bound to the radiotracer in the postpartum group than in the controls, with significant differences seen in all the brain regions measured (prefrontal cortex, anterior cingulate cortex, anterior temporal cortex, thalamus, dorsal putamen, hippocampus, and midbrain).

The findings mesh with a wealth of literature confirming the relationship between depression, low neurotransmitter levels, and MAO-A levels, Dr. Meyer noted, as well as with an entire class of antidepressants aimed at inhibiting the enzyme.

"I’m not saying this is the only mechanism" underlying postpartum mood changes, he noted. "But this is an important one, because there is a strong magnitude of effect, and MAO-A is a target that directly affects mood. This is something we should be looking at.

"We give women all kinds of recommendations during pregnancy," such as iron to prevent anemia and folate to prevent neural tube defects. "But no one has ever said to a woman, ‘Look, there is a biological underpinning for the sadness you might feel after delivery, and here is something we might be able to do about it.’ "

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