There’s a 50 percent chance of recurrence in 1/3 of pregnancies and for non-postpartum mood disorders, a 35 to approximately 45 percent rate of recurrence. Now, with respect to the circadian rhythm basis for these mood disorders, estradiol and progesterone change dramatically during pregnancy and drop precipitously postpartum.
Estradiol and progesterone regulate the circadian rhythms of melatonin in sleep. Normally, melatonin and sleep are synchronized so that melatonin goes up a couple of hours before sleep, peaks during the mid-sleep time, and then come back down in the morning.
But with the change in reproductive hormones, melatonin can be shifted later with respect to sleep or it can be shifted earlier with respect to sleep. Likewise, sleep time can become desynchronized with respect to melatonin, the sleep can be shifted later, or it can be shifted earlier.
When we studied melatonin rhythms, which is the best measure of circadian rhythms in humans, in plasma, you can see the normal in the yellow rhythm of melatonin but in the depressed patients, that melatonin rhythm is lower and shifted earlier.
Melatonin is an important contributor to synchronizing other rhythms in the body. For those women who have a personal history of depression, that rhythm is shifted earlier. The more depressive episodes a woman has had, the early her melatonin offset time is.
But if you want to ask a question or read answers that provide a piece of good information related to Peripartum depression or anything related to it there are some QnA sites that offer that kind of services and Ask Reader is one of them.
So it’s not just a fleeting abnormality. In contrast, postpartum women, in contrast to the pregnant depressed women, and normal controls, have higher levels of melatonin, particularly in the early morning hours that are shifted later or phase delayed.
Across pregnancy, in the left panel, as estradiol and progesterone increase dramatically during pregnancy, the melatonin levels increase in normal controls.
But in the depressed pregnant women, there is though their melatonin isn’t getting that signal increase, so there’s less melatonin rise across pregnancy, impairing the ability of melatonin to synchronize other rhythms.
In postpartum, normally as the estradiol and progesterone levels decrease, then the melatonin levels tend to decrease in the normal controls, but that signal doesn’t seem to be communicated in the depressed patients so their melatonin levels continue to rise. The treatment of peripartum depression.
There are multiple treatments. I don’t have time to review each of these treatments, but I want to make the point that, it’s much more serious for a woman not to be treated for depression either during pregnancy or postpartum.
That has adverse consequences on both the fetus and the developing infant and can cause emotional and neurocognitive development delays and problems in the now been studied for up to at least 17 years after delivery. So none of these agents used to treat postpartum depression have serious teratologic risks.
So, again, it’s much better to treat than not to treat, but they do have side effects. We’ve been looking into examining shifting sleep and light schedules to re-synchronize abnormal circadian rhythms. The idea is that in a normal happy camper on the top panel, the sleep in the circadian clock is measured by melatonin, which is in phase.
Sometimes the clock can be delayed. Progesterone tends to delay circadian rhythms. So we treat that by giving bright morning light, which can correct that disturbance. If the sleep is advanced, then we delay sleep to correct that disturbance.
If the circadian clock is advanced, then we can give evening light, bright light, which delays circadian rhythms to correct. If the sleep is delayed, then we advance sleep to correct the disturbance. Now, one of life’s great paradoxes that if you take a depressed patient and you keep them up all night, the majority of them are better the next day.
That was discovered in Europe where patients with bipolar illness, the nurses noticed before they switch from depression into a mania, they were up all night. So if they took a depressed patient and kept them all up all night, there were better the next day.
The problem was they would often relapse as soon as they went back to sleep, even for a few minutes of rapid eye movement or REM sleep. Subsequent studies have shown you don’t need to be up the whole night, that only half the night is required to convert a depressed patient or treat them with a half a night of sleep restriction.
So a majority of depressed patients do respond to what we call rather than sleep deprivation, wake therapy. The effects may occur in one.
Some but not all patients may relapse when they go back to sleep and some, but not all studies suggest that the wake therapy in the second, but not the first half of the night might be effective, but that may depend on someone’s underlying circadian rhythms.
We wanted to try this treatment in peripartum depression. Sleep disturbance characterized pregnancy and postpartum depression, even when the child is sleeping postpartum.
I don’t have time to present the evidence of sleep disturbances at this time, but there is a concern, is mentioned with using pharmacological interventions because of the potential effects on the fetus and infant, and critically timed wake therapy may offer potential benefit within one day. How does this work? We think that this may realign sleep and the circadian cycle.
It may suppress rapid Eye movement sleep or REM sleep, all antidepressants virtually suppress REM sleep and if you just suppress the REM sleep, you get antidepressant effects. At the same time, it takes an anti-depressant to work, which is several weeks.
It also may increase what we call the homeostatic drive. The longer you’ve been awake, the more likely you are to go to sleep and then improve your sleep quality. These wake therapy interventions also make changes in the neuroendocrine system, particularly the thyroid system.
So we examined, took pregnant depressed women and postpartum depressed women, and they underwent a night of either late wake therapy, where they’re awake in the second part of the night and they sleep in the first part of the night from 09:00 PM to 1:00 AM or early wake therapy where they are awake in the early part of the night and they sleep in the second part of the night from 3:00 AM to 7:00 AM.
We found that in the pregnant women, depressed women, responded better to the early night wake therapy, whereas the postpartum women responded better to the late wake therapy. That may be because it’s correcting the circadian rhythm abnormality.
In pregnancy, the rhythms are shifted earlier, so we delay sleep. In postpartum, depressed women, the rhythms are shifted later so we advance and restrict sleep.
For the clinical bottom line for pregnancy depression, one night of early night wake therapy, you’re awake until 3:00 AM and sleep until 7:00 AM. For postpartum depression, you one night of late-night wake therapy where you go to sleep at 9:00 PM and wake at 1:00 AM. We avoid, encourage avoiding naps and if needed, repeat it in one week.
But some of these interventions have worked up to six months and afterward. Now, to address the issue that after wake therapy some patients may relapse, one way of preventing that relapse is adding light therapy. So using the combination seems mutually advantageous.
Wake therapy will hasten and potentiate the effects of light therapy, which another map wise may take like five weeks to exert its significant antidepressant effects. Then light therapy prevents the relapse that may occur after wake therapy.
Phase-advancing or shifting earlier versus phased delaying, shifting later, the wake and light interventions help to realign disturbed melatonin and sleep circadian rhythms. So they’re more potent effects of this combined therapy.
The conceptual model is that at baseline in pregnant women, the circadian rhythms are shifted earlier or phase advanced with respect to sleep so we delay sleep and we get evening light, which helps to delay circadian rhythms.
This correction of the sleep and circadian rhythm dysfunction improves and we get an improved mood and sleep function. In contrast, in postpartum depression patients, melatonin rhythms are phased, delayed, or shifted later with respect to sleep.
So we advance sleep in a phase-advance intervention and give morning bright light, which advances circadian rhythms. It says, result, we get an improved function and mood and sleep as a result of phase-advancing melatonin rhythms relative to sleep.
In fact, this is what we observed in pregnant women, they had a positive response to the early wake therapy plus the pm evening bright white light and in contrast, the postpartum depressed patients did better with late wake therapy and morning bright white light.
The treatment implications for combining sleep and light therapy in depressed women, that when the circadian rhythms of melatonin or phase delayed or shifted later and we have found this in pre-menstrual depression, postpartum depression, and menopausal depression, we advance and restrict sleep and give morning bright white light.
With the phase advanced melatonin rhythms that are shifted earlier, like in pregnancy, we delay and restrict sleep and give evening bright white light.
We can get an effect within one day and then maintain that effect since you make the diagnosis of depression over two weeks, we get the effect within one to two weeks. The improved mood correlates with the change in melatonin.
These treatments may have positive benefits, your mother just wants to let you know that she’s finally over her postpartum depression.
This is nothing new, as Solomon wrote in Ecclesiastes, “Truly the light is good, and it is pleasant for the eyes to behold the sun.” If we ever intend to take over the world, one thing we’ll have to do is synchronize our biological clocks and I wanted to emphasize not just women who suffer postpartum psychosis, this is a sketch of Theseus Tas.
He suffered a postpartum psychosis at the birth of his third child and killed his wife and all three children. He went to the ruler Theseus and to make penance, he was given this pass of Hercules.
