SAGE ELEVATE PRESENTATION ENDURING RESOURCE Slide Transcript Slide 1 e. Dr McIntyre: I'm a psychiatrist. I am a professor of psychiatry in Toronto. I'll give a very brief and pithy introduction to my colleague, Dr. Jamie Maguire, who is very local - Tufts University associate professor of psychiatry. And we're going to be sharing with you in this very brief presentation the topic of postpartum depression. It's a topic I don't think I need to spend a lot of time on in pressing upon you how important this is. For the last 20 years I have been running a very large mood disorders program with the University of Toronto. We have had several thousand patients over the years who have first presented with postpartum depression. I would say in the last five to 10 years we've learned more about this topic and the pathoetiology of this topic than we have in the previous two or three decades combined. This information is now guiding us towards very novel ways of helping people who have this condition. Slide 2 Now, the company who is supporting this presentation is Sage Therapeutics, and both Jamie and myself are supported by this company so you should know who your spokespersons are today and who they are working with so we have these conflicts to disclose.
Slide 3 This is a brief resume. I'm in Toronto. Jamie is very local here in Boston at Tufts University. Slide 4 Let's, if we can, just begin to set the stage or really describe the topology of the land here. We want to talk about postpartum depression. You're going to see this acronym, PPD, throughout the slides. We're going to talk about the prevalence of this condition. We're going to talk about some of the disease models that have been put forward to help us understand postpartum depression. Then we're going to move in to some very nice data that, frankly, Jamie has been leading this area scientifically - helping us understand the molecular as well as some of the endocrine aspects that are subserving this phenomenology. Then we'll get into the treatment. Slide 5 Let's talk about facts and figures.
Slide 6 The DSM-5 does not have postpartum depression as a discrete entity but has it listed as a specifier. In other words, if you have depressive symptoms during pregnancy or within four weeks of delivery that would meet the criteria for puerperal depression or postpartum depression. Other documents like the ICD-10 have longer windows. Up to six weeks in the case of the ICD. The World Health Organization extends it out to 12 months, but the point is that we have this entity described in the DSM-5. With respect to differential diagnosis the key differential diagnosis is, in my view, bipolar disorder. So any patient you see who presents with syndromal depression in that postpartum period, you've got to be thinking about bipolarity given the very high probability that many individuals with postpartum depression do have bipolar. Slide 7 The differential diagnosis is what I call the trifecta. You've got postpartum depression, you've got the postpartum blues, and you have this postpartum distress or, in some cases, a full-blown trauma that can be recapitulated. Postpartum blues is very common. Fifty to 80 percent of women will have this. It tends to start after birth and usually resolves within a couple of weeks. That is very different than a syndromal depression that persists and is often accompanied by very severe levels of impairment. That's the part that I've been quite struck by.
Slide 8 But here is what I think is the takeaway message. When asked, "What is the most common complication of pregnancy or postpartum?" It's depression. It's estimated that between 8 and 20 percent of women experience postpartum depression. Statewide rates have varied. Most rates coming in, in this 10 to 12 percent range. It's more common than diabetes during pregnancy. More common than hypertension. More common than eclampsia. All these conditions that we hear about, we've been trained about, we're paying attention to are less common than postpartum depression despite the high prevalence in its rank order as being the most common problem of pregnancy postpartum. It is often the case that women are not accessing care specifically for this problem. Only 10 to 12 percent of women actually access care for this problem. Slide 9 Now, this is a statewide look. This is a portrait obviously, of the U.S. The point is, is that this is a cross-national phenomenon. It's an international phenomenon cutting across sociodemographic categories. All cultures, all races regardless of education. This is an enormous statistic that almost half a million women will be affected by postpartum depression.
Slide 10 Now, the implications to mom are obvious. You have this condition which is a serious brain-based disorder. That being depression, and that's often associated with suicidality and, obviously, impairment in quality of life and function. Along with that there's often maladaptive behaviors that are recognized as increasing during this time. Not only smoking of cigarettes, but more commonly the misuse of alcohol. We also know that because of postpartum depression or associated with it we see much more pre-term delivery. Small for gestational age and certainly, underweight infants. Certainly, this is a serious issue indeed. Slide 11 Now, in a larger forum, in perhaps, a less distracting environment we would have had a lot more time to go through this slide which I think is really, an incredibly educational slide. The message for me is trajectory. Whether it's the short-term meaning in the first month to two months where attachment begins to be realized. In the more intermediate term, that is, within the first few years of life around emotional development, cognitive development, and certainly, behavioral development. What we recognize in children of moms with postpartum depression is they begin to exhibit what we call off-trajectory. There's abnormalities observed. These could be interfering with function, and this can be manifested way out until the teenage years with respect to a higher risk of mental illness. Said differently, there's implications for mom, that mom/child dyad, and that unfortunately, creates a scenario for the child increasing the risk for off- trajectory development.
Slide 12 I'm going to stop there, pass the podium over to Jamie, and Jamie is going to take us through what mice can tell us. At least the data around mice. So Jami e…. Dr Maguire: Thank you so much. My name is Jamie Maguire, and I am an associate professor at Tufts University right down the street. The goals of my lab are to study how stress and GABAergic dysfunction can contribute to neurological and neuropsychiatric disorders. One of the major focuses of my lab is postpartum depression and major depression. Slide 13 The reason that we're interested in the GABAergic system is it's the primary inhibitory nerve transmitter in the brain. It is mediated by GABA receptors that have unique pharmacology. Many of the drugs that we use act on these specific receptors. There's unique receptors that are sensitive to neuroactive steroids, derivatives of steroid hormones that can act on specific subtypes of GABA receptors and potentiate the inhibitory effects of GABA. Other separate subsets of the GABA receptors are sensitive to benzodiazepines. These inhibitory actions can inhibit neuronal function but can also coordinate activity across brain regions. We are interested in how these GABA receptors play a role in coordinating activity across brain regions including limbic regions that are important for affect. We're interested in the amygdala, prefrontal cortex, hippocampus - brain regions that have been implicated in mediating affective behaviors - as well as the paraventricular nucleus of the hypothalamus. The paraventricular nucleus of the hypothalamus regulates the stress response. It coordinates the hypothalamic- pituitary adrenal axis and CRH neurons. Corticotropin releasing hormone neurons reside in this area. They're at the apex of HPA axis control. We're really interested in how the GABA system can regulate stress reactivity and therefore, also influence circuits that are important for affective disorders. These neurons, these CRH neurons that control stress reactivity are tightly controlled by GABAergic signaling. Over 50 percent of the inputs on to those neurons are GABAergic so
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