Video Transcript

Hello, I'm Jeremy Schreiber, psychiatric mental health nurse practitioner.

As of late, there has been considerable debate as to whether or not postpartum depression and major depressive disorder are separate and distinct illnesses or whether or not they should both carry the same diagnosis. I think when we think about postpartum depression and major depressive disorder, it's also important to understand that there is a high degree of morbidity and mortality associated with the postpartum period for both the mother and the infant.

This being said, it is also important for us to review the context when we think about the neurotransmitter systems, and we also think about the pathways on which these neurotransmitters work. In addition to that, we should be thinking about the role of serotonin in GABA in patients that have both depression and postpartum depression or postpartum depression, I should say. When we think about this, we should understand that these two conditions have some similarities and overlaps, but we should also understand that these two conditions have a distinction between them both.

Women with postpartum depression do have changes in the GABA system, and it's related to hormones, progesterone breakdown, or what I would call the metabolites of progesterone, such as allopregnanolone. And these patients, much like patients with depression, can experience some similar symptoms. However, there are differences between the two conditions. Women with PPD do show a dampened GABA system, which also affects emotional salience, and when we're looking at this, they may be less responsive to infant distress.

This being the case, when we think about major depressive disorder and postpartum depression, these two disorders, while they overlap, do have some differences between them. When we think about the neurotransmitters involved, and we think about the heterogeneous presentations of both postpartum depression and major depressive disorder, we can understand that these two disorders do have symptom overlap. And when we think about the neurochemistry and that these are multifaceted symptom presentations, we can understand that there's also enough evidence to support that these two disorders are related as well.

So, when we think about why postpartum depression and major depressive disorder, when we think about why there may be some debate as to whether these are the same illness or different illnesses, or different disorders, we can appreciate that neurotransmitters are involved in both depression and also in postpartum depression. However, when we think about what neurotransmitters are involved in the etiology or kind of the pathophysiology of the neurotransmitter systems, we should be thinking about what's happening in the brain.
One thing to consider is that when we think about depression, depression can present a lot of different ways, and with depression presenting a lot of different ways, we know that there could be imbalances or reductions in the amount of serotonin, norepinephrine, dopamine, things of these nature, the monoamines that are contained within the synaptic cleft. However, with postpartum depression, what we're actually looking at is that there is a rise in the rates of progesterone and allopregnanolone in patients who are pregnant. When these patients deliver, their levels of allopregnanolone and progesterone decrease, and they decrease rapidly. However, when the patient first becomes pregnant, the levels of allopregnanolone and progesterone rise rapidly. Well, allopregnanolone and progesterone, or allopregnanolone, is a GABA kind, which means that it has stimulatory effects on the GABA system.

Now, we also have to think about the balance between GABA and also glutamate. Glutamate is the primary excitatory neurotransmitter, and GABA is the primary inhibitory neurotransmitter. If we have too much glutamate, we end up having a seizure. If we have too much GABA, we end up with respiratory depression, and we die. Well, during pregnancy, the levels of allopregnanolone and progesterone rise, and when these levels rise, what happens is the body has to compensate by decreasing the amount of GABA receptors.

Well, in postpartum depression, when the woman delivers, what happens is the levels of progesterone and allopregnanolone fall very, very rapidly. When these levels fall rapidly, the body would then turn around and want to recompensate by increasing its GABA receptors. However, the time that it takes to increase GABA receptors is much longer than the time that it takes to have the reductions in GABA take place. And so, we have patients end up with postpartum depression related to these GABAergic or the GABA system as well. The GABA system is also involved in depression, and we really should think about the GABA system as well because two-thirds of all neurotransmitters, or two-thirds of all synapses in the brain, are actually either GABA or glutamate. Again, the primary excitatory and the primary inhibitory. Take in mind excitatory means that it's going to cause other neurons to fire, and inhibitory means it will tell other neurons not to fire.

Some of the adverse effects of postpartum depression on both the mother and the infant are things like poor bonding between the two. If a mother has postpartum depression, that mother may be less responsive to respond to her baby. Additionally, some other things that happen are parents tend to stop thinking about themselves. Mothers may put the care of the infant first, and the mother may also have postpartum depression that goes unrecognized, undertreated. It's oftentimes not caught by their obstetricians, by primary care, by us in psychiatry. Actually, postpartum depression is most frequently caught by pediatricians, and it's the pediatricians that are seeing the infant.

But the thing is, when we think about the development of the baby, what we're looking at is how does this baby develop over the course of time? And the problem is that in mothers with postpartum depression, there can be a lasting impact on the infant and on its development through the course of its life. So we can see problems into adulthood. Early on, we may see things with bonding or bonding problems. We may have sharing problems. The children may not meet their milestones, such as stacking blocks or building bridges, but it's not just the psychiatric issues with depression. It's also medical conditions as well that these young babies, as they grow into adulthood, will suffer with. Children born to mothers with postpartum depression are also more likely to experience depression during their lifetime.

Another point that I want to make is about the serotonin and the GABA system. So, if we think about the serotonergic system, we have to understand that what we're looking at is a reduction in the monoamines. In the normal brain, we have healthy amounts of monoamines, and these function on the receptors, and this is going to make us feel normal. In patients with depression if we think about the monoamine theory, patients with depression are often going to have reduced amounts of these monoamines.

Now, this can also happen in postpartum depression. You remember I talked about how the levels go up of allopregnanolone and progesterone, and so forth, in patients when they become pregnant and fall. But when these levels fall, the body wants to return to the right balance. In essence, its GABA and its glutamate want to return to be at an even balance. This would happen in most cases when there's not other things that may be out of whack. In patients that are under chronic stress, the other neurotransmitter systems may not be where they need to be, and the body may not be able to adapt back to have the healthy balance between GABA and glutamate. So, GABA and glutamate are implicated, especially GABA is implicated in depression, in major depressive disorder, and also in postpartum depression, as are the neurotransmitters as well.

In terms of the circuitry involved in depression, we have to understand that we have a default mode network, a salience network, and a central executive network. Now your default mode network is going to be responsible for looking at internal stimuli. And when the default mode network is out of whack, patients may be more likely to be ruminative. And when we have in the CEN, what we have is this is pays attention to our outside influences, so external stimuli. And it's the salience network that kind of allows these two networks to determine if we should be focusing on internal stimuli or external stimuli. So, for instance, if we are focusing on our external stimuli, the CEN is active, then we may not be processing what's happening internally, such as responding to the cries of an infant. And we may not be up seeing these patients.