postpartum mood

Perinatal Mood, Cognition and Hormones

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While searching through old research files for an article I am writing on mitochondria and hormones, I stumbled upon the presentation notes for my thesis defense. I thought some of our readers might find them interesting. Although, I was not able to find the original PowerPoint presentation, I did find a later presentation that included my thesis and dissertation research, along with the some background information on neuroendocrinology. You can read my thesis here and/or the articles published from that research here and here. I added a few subheadings for readability, but otherwise, the presentation remains unchanged.

Perinatal Mood, Cognition, and Hormones

The purpose of this study was to identify the cognitive and emotional changes associated with pregnancy hormones both during pregnancy and postpartum and to identify early markers for perinatal mood dysfunction.

This research was based upon several physiological presumptions regarding pregnancy and postpartum. Conventional wisdom holds that during pregnancy reproductive hormones increase exponentially to support the pregnancy. It also posits that after delivery those levels decrease rapidly to below normally circulating levels and remain low until breastfeeding ceases and menstruation begins.

Animal research shows that many reproductive hormones are neuroactive and potently modulate numerous neurotransmitters systems. Given the large and sustained increased in such hormones followed by the precipitous decline, one would expect clear behavioral changes associated both with the elevated and diminished states of circulating hormones. We would also expect that the change from high hormone to low hormone state would mimic an addiction/withdrawal syndrome.

Numerous animal studies indicated that this was the case, but the connection between hormones and behavior in human studies was inconsistent and inconclusive for many reasons outlined in my research. The most important failing of previous research has been the lack of theory or evidence-based design. That is, not only has previous research failed to recognize, and hence, postulate neurosteroid/neurotransmitter mediated behaviors, but often failed to recognize the clearly articulated affective dysregulation presented regularly in clinical case research.

The question of which hormones modulate which neurotransmitters and to what behavioral consequences has not been asked, nor has the possibility that perinatal mood might be altered across several domains ever been addressed. Instead, most if not all, research focuses exclusively on progesterone and estradiol without so much as even speculating which neural circuits might be involved. Moreover, despite ample clinical evidence to the contrary, most research thus far measured and continues to measure only anhedonic depressive symptoms.

This study was different. Because extensive clinical case research revealed that perinatal mood was more often than not comprised of multiple syndromes of which depression was merely a part, I expanded the psychiatric domains measured to include assessment of 9 common psychiatric modalities and utilized a standardized and validated measure.

Additionally, previous studies measured only progesterone and/or estradiol. This study measured five hormones, progesterone, DHEAS, estrone, estradiol, estriol and testosterone.  The timing of assessment in other studies has been inconsistent and again not obviously evidence based. With approximately, 70% of all cases of postpartum psychosis occurring in first two weeks post-delivery, I thought it was important to measure within that time frame to capture those changes. Since case reports reveal premorbid symptoms during late pregnancy, I also measured at 37 weeks of pregnancy.

This study utilized salivary assays to measure hormone levels and controlled time of day and food intake. All previous studies measured hormones at non-standardized times and did not control food intake. Hormones have diurnal rhythms, and food intake, particularly with salivary assays will comprise results.

But perhaps the most important difference between this and previous studies is that this study was designed, all instruments were selected and the timing of testing was determined, based upon the presumed neuromodulatory activity of these hormones and the predicted concomitant behaviors associated therein, using an addiction/withdrawal framework. Thus it was imperative to test in the immediate postpartum so as to capture changes before neurological and behavioral adaptation occur.

It’s All About GABA

Given these considerations, much of the study design was based upon progesterone’s capacity to modulate the GABA system.

Progesterone is a potent allosteric GABAa agonist and anxiolytic. However, chronically elevated progesterone becomes anxiogenic via its actions on receptor conformation. It was postulated that during the course of pregnancy, the women would be the beneficiaries of the progesterone’s anxiolytic actions, but that towards the end of the pregnancy, as receptor conformation changed, the GABAa receptor would become immune not only to progesterone’s actions but GABA’s actions as well with the net behavioral effect of increased anxiety.

Postpartum, when progesterone was withdrawn the lack of CNS GABA transmission would induce hyper-excitability across several CNS systems that would be expressed in elevated anxiety symptoms and mood lability.

Major Findings: It’s Not Progesterone or Estradiol and It’s Not Depression

What I didn’t know going into this study was that DHEAS also modulated GABAa but did so antagonistically. What I also didn’t know, and what is in fact the first major finding of this study, was that circulating DHEAS levels increased throughout pregnancy and postpartum. All previous research indicated that DHEAS increased over the first two trimesters, decreased during the third and returned to normal immediately proceeding delivery. This was not the case. Although I have only two test times, DHEAS levels were clearly very high at 37 weeks, and increased postpartum by an average of 34%. Indeed only 6 participants showed waning postpartum DHEAS levels.

Returning to the GABA hypothesis, as is now becoming clear, during most of the pregnancy progesterone positively modulates GABA transmission. Toward the end of pregnancy when progesterone levels presumably level off but are nonetheless at supra-physiological levels, the chronicity of exposure elicits conformational changes in the receptor making it unresponsive to progesterone and according to animal research unresponsive to benzodiazepines as well. Concurrently, DHEAS levels are increasing and are now blocking whatever limited GABA transmission exists. Parturition occurs, progesterone levels diminish by some 93% while DHEAS levels continue to increase. So now whatever remaining GABA binding sites are still available become blocked and CNS hyper-excitability ensues leading to the behavioral lability seen in almost all women during the first two weeks postpartum.

The behavioral sequelae of these rather dramatic physiological changes include increased anxiety, phobia, OCD, paranoia psychoticism, and importantly many physiological symptoms tapped by the somatization scale of the SCL-90R, particularly cardiovascular dysregulation, increased heart rate, respiration, sweating, etc.

Postpartum, even in asymptomatic women, that is the 80% of women who experience what is imprecisely called “baby-blues” is often marked by hyper-excitability and mood lability as much or more so that anhedonia and depression. This is with good reason given the neurochemical and physiological changes occurring as these hormones adapt to the non-pregnant state.

Thus, the second major finding in this study was that although depression was certainly present, it was by no means the sole determinant and I would argue not even the primary or causative factor in the observed mood dysregulation postpartum. This is really important because insofar as previous and indeed current research continues to focus on postpartum depression rather than perinatal mood more broadly, hundreds of thousands of women get misdiagnosed, under-diagnosed and inappropriately treated. The findings from this study indicate that not only do negative mood symptoms begin in late pregnancy but that the disorder itself is characterized as much by anxiety or positive type symptoms as it is by depressive and anhedonic type symptoms.

The third major finding of this study was the connection between late pregnancy and post-delivery hormones to negative mood. As was outlined in my research, the design of this study was very strongly based upon the neuromodulatory capacity of progesterone on the GABAa system. Results from this research indicate that progesterone was not correlated with negative mood and thus I was wrong about progesterone. Nevertheless, I was correct about GABA being a major player in perinatal mood dysregulation.

Recent research suggests that DHEAS is a potent GABAa antagonist similar to the drug picrotoxin. That is, it is capable of binding to a site deep within the receptor, thereby limiting GABA influx.

Given DHEAS’ influence on GABA, its increase late pregnancy and post-delivery, one would expect clear and consistent correlations between DHEAS levels and mood. That is exactly what I found. Pre-delivery DHEAS was correlated with paranoia and psychoticism.

Post delivery DHEAS was strongly and significantly correlated with just about every mood symptom measured by the SCL-90R including anxiety, phobia, paranoia, somatization, and the GSI. Recall that DHEAS levels increased an average of 34% and increased for all but of 6 of the women postpartum. In some women, those who had the most severe postpartum difficulties, DHEAS levels increased 2-4X pre-delivery levels.

Moreover, the fourth major finding from this research showed that pre-delivery testosterone was correlated not only with pre-delivery negative mood (phobia, psychoticism, somatization and GSI), but was correlated strongly and significantly with almost every negative mood symptom measured by the SCL-90R post-delivery as well, including anxiety, hostility, psychoticism, somatization, OCD, interpersonal sensitivity, depression and GS. And the correlation was negative. That means that diminished testosterone (amidst the presumably elevated levels of pregnancy) were correlated with increased negative symptoms. This is important for a number of reasons, not the least of which is its predictive possibilities, but it suggests that the adrenal androgens of which DHEAS and testosterone are key component are implicated in perinatal mood.

This is groundbreaking. It has never been addressed before in the literature. If we look at the biosynthesis of steroid hormones during pregnancy, we see that DHEAS is produced both by the fetal and maternal adrenals and is intra-converted in the placenta as well. Biologically, DHEAS is considered inactive, meaning that it must be converted to DHEA before other downstream hormones can be metabolized. DHEAS is storage component for DHEA. If more DHEA is converted to DHEAS, for whatever reason, then less downstream hormones-testosterone are synthesized. These are the results I found. Since I didn’t measure DHEA, I can only speculate, but these two factors in hormone synthesis appear to be altered and these alterations are related to the mood perinatal mood dysfunction. Future studies are needed to confirm these findings and determine their etiology but preliminarily these results open up an entirely different direction for future research that has yet to be addressed, the implications of which will be far-reaching.

Perinatal Cognitive Changes

The cognitive results from this study were no less impressive but not as easily interpreted because cognitive ability was not consistently linked to either mood or hormone data but was obviously impaired.

As a group, these women were educated with many having graduate degrees. The average estimated IQ was approximately 1 SD above the mean and might have been higher if complete testing had been performed. Most of these women worked outside the home in a professional capacity for the duration of their pregnancies, and yet when tested, showed significant memory and executive function deficits when compared to age and education matched normative data. The degree of impairment was striking, and quite frankly, unexpected.

In verbal memory measured by the CVLT-II, many percentile rankings were below the 20th percentile. When testing these women, it became apparent how important semantic memory was, with those women recognizing the categories of words having little difficulty completing the task and probably skewing the data somewhat. However, for a large percentage of the women, there was absolutely no recognition of the categories inherent in the task and their ability to recall even a fraction of the words was hindered tremendously. The women also repeated words, in some cases 2 and 3 times during the course of a trial and recalled words that were not part the trial list.

On spatial memory tasks the deficits were no less obvious. As is exemplified by the CFT tasks, shown in the appendix of my thesis, the impairment was at least in part related to an inability to see the drawing as an entirety. If we look at these drawings closely, we see that in the copy phase, the core of the drawing, the rectangle is missing. That is, each section of the figure is drawn separately. This presents difficulties in encoding that will ultimately limit performance of the recall portion of the task. Again notice the piece meal quality of the figures in the recall task, with large portions of the figure completely missing. The examples illustrated here are representative of performance across participants.

The mood to cognition relationship was interesting if not paradoxical. Conventional wisdom would suggests that negative mood, particularly depression and anxiety would impair cognitive performance. This was not the case. Indeed depression actually improved performance.

The hormones to cognition relationships were no less confusing except that changes in DHEAS were correlated with poorer performance on the CVLT-II. Given the magnitude and direction of change in DHEAS levels this was consistent with the earlier results. Progesterone, was not correlated with mood symptoms but was correlated to both aspects of the design fluency task and the estrogens were correlated with a variety of task both pre and postpartum.

What was particularly interesting about this aspect of the research was that cognitive ability declined in many areas postpartum, but participants perceived themselves as having improved. The disconnect between perception and performance was clear almost across the board.

Finally, it may be that as in the case of other mental illnesses, cognitive functioning is not correlated with severity of symptoms but is associated with measures of therapeutic outcome such that higher premorbid functioning predicts one’s ability to function during and after an episode.

This possibility begs the question that if another group of women was tested having lower premorbid cognitive function and lower socio-economic status, would they have fared as well as the women in this study. That is, would their ability to withstand the physiological and consequent emotional/behavioral change associated with pregnancy and postpartum be comparable to the abilities of this group?

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The studies addressed here were published in 2007 as part of my PhD dissertation. This post was published on HM on November 29, 2018.

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Beyond Depression: Understanding Perinatal Mental Health

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In part one of this series I noted that my approach to postpartum depression research was a little bit different than most others. Namely, I didn’t ascribe to either the nomenclature of the syndromes, whether defined by popular culture or by the DSM, the timing of the onset of the symptoms nor the explanation of the causes. I think the symptoms are largely hormone related, and as such, ought to be distinct entities diagnostically. That requires understanding, testing and then defining the spectrum of symptoms and their relationships with individual and hormone patterns. I’d like to discuss symptoms first, even though this particular research was conducted after finding hormone – symptom relationships and informed by the patient stories collected in conjunction with that research.

Postpartum Depression or Not?

Not, but with a caveat.

As I accumulated data for my hormone symptom study, those data along with participant stories led me to design a broad-based symptom study for postpartum women (this particular study did not include pregnant women, as some my other studies did). I wanted to test whether the typical designations of postpartum depression clustered statistically within discrete but consistent diagnostic categories. Did postpartum depression exist and if so, did the symptoms mirror those in the DSM or in the popular science? Or was depression just one among many types of symptoms that emerged and how would those symptoms fall together statistically? In other words, I wanted to test what the women were telling me about their experiences and against what my other data were showing. The study:

Dimensions of Postpartum Psychiatric Distress: Preliminary Evidence for Broadening Clinical Scope

Study Basics.  The study was online with questions covering nine dimensions of postpartum mental health that I had found relevant in previous work: depression, anxiety, mania, psychosis, obsessive-compulsive behavior, self-image, social support, mental status and perceptions of motherhood. The questions were retrospective and the participants were asked to rate the frequency of symptoms experienced over the first 30 days following childbirth on the following scale: 1-never, 2-occassionally, 3-frequently, 4-most of the time.  We had 215 women complete the survey. From those data we did an exploratory factor analysis (EFA) to see how the symptom data grouped itself statistically. Did the symptoms group by established psychiatric dimension e.g. depressive symptoms in a depression category, anxiety symptoms with the anxiety category, psychosis with psychosis, etc.? Or would the symptoms group in some other manner?

Results.  As I expected, the standard categories were not statistically grouped. That is, there was no such thing as postpartum depression or postpartum anxiety or postpartum psychosis. Rather, there were unique clusters of symptoms that grouped together and contained aspects each traditional symptom category. The EFA data revealed 10 new and distinct factors or symptom groups. Most telling were the first three factors or groupings: mental status, psychoticism/morbid thoughts and a general anxiety. Notice, I didn’t find a depression grouping. Indeed, depressive symptoms were interspersed throughout the 10 categories, but most densely and the most severe within the psychoticism group. Let me explain. Here are the 10 symptom groups or factors, listed in order of importance or prominence (variance accounted for):

  • Mental status – This was the most prominent cluster of symptoms, with upwards of 40% of the women reporting difficulty with two primary areas of mental status: memory and attention, and motivation – or lack of motivation.  Some of the symptoms ascribed to within this group included: difficulty completing simple tasks and staying focused, mind going blank, difficulty organizing thoughts, losing track of time, no motivation, difficulty expressing thoughts, fatigue and loneliness among others. From other research conducted, we know that measurable cognitive difficulties, especially those associated with attention and memory, are common problems amongst pregnant and postpartum women. That this was the highest ranked factor, meaning that it accounted for the most variance, was consistent with my previous work.
  • Psychoticism and morbid thoughts – This was the most striking category and accounted for what many would consider the most troubling symptoms. This factor grouping included everything from intrusive and morbid thoughts, to hallucinations and suicidality.  It truly represented what would have been the most serious of psychiatric conditions but was not akin either to a strictly depressed state or psychosis in the most traditional sense or even to an obsessive compulsive disorder, emphasis on obsessive. Rather it had components of each, uniquely focused on the maternal state. Some of the symptoms ascribed too included: images of the baby being stabbed or thrown out of a window, fear of harming the infant, thoughts of violence, hearing voices to harm myself or others, inability to keep bad thoughts out head, afraid to be alone with baby, afraid of harming self, frightening dreams, the feeling that others want to harm me (the mother) or the baby, feelings of terror, no hope for the future, feel like someone is controlling one’s thoughts, worrying that the infant will suffocate.
  • General Anxiety – this grouping of symptoms is what I believe may represent milder forms of distress that to some degree all women feel as they enter into motherhood. Some of the symptoms include: ‘I believe others see me as a bad mother’,’ I think I am a bad mother’, confusion, no confidence, overwhelmed, mind racing, losing control, constantly being judged, no one understands me, among others.

The remaining seven factors or groupings were somewhat more specific to traditional psychiatric categories but also included psychosocial aspects relative to self-image, relationship and social support. They also accounted for far less statistical variance, indicating some degree of specificity to certain groups of women rather than being applicable to most postpartum women and/or were far less relevant to the overall distress. These groups included:

  • Panic – fear of large crowds, fear of leaving the house, feeling keyed up, restless, on edge, skin crawling
  • Guilt and emotionality  – a range of guilt related feelings, but also, mood lability – switching from happy to sad, quickly and frequently
  • Compulsive behaviors  – cleaning and checking
  • Hyper-vigilance  – a sense that the new mom was the only one who could care for the child
  • Contentment  – positive relationship, social support, and general well being
  • Negative self-image – range of negative self-image attributes, along with a sense that her body was shutting down –that something was wrong with her.
  • Mania – hyper excitable, excessive energy despite a lack of sleep, impulsive behavior

What Does This Mean?

The results from this study suggest that neither the current diagnostic categories nor the popular nomenclature appropriately categorize the types and severity of postpartum related mental health issues. Depressive symptoms were neither the most common symptoms nor contained within a defined category. Rather depressive symptoms were interspersed throughout each category with the most severe depression symptoms, loss of hope and suicidality loading to the psychosis/morbid thoughts category. Along with the more severe depression symptoms, this category contained hallmark psychosis symptoms like hearing voices, seeing things, but also what could only be described as violent, frightening intrusive thoughts.

What was particularly interesting is that mania, which has long been linked to postpartum psychosis, was neither present in the psychosis/morbid thoughts category nor accounted for much variance at all within this study. This could mean that mania is not a common component of the most serious forms postpartum distress for most women, but rather a distinct subset of the disorder. Instead, it may be the violent intrusive thoughts and the hallucinations that are associated with the most serious symptoms of depression – the suicidality. From these data, the postpartum spectrum is not from mild sadness (baby blues) to more intense sadness or postpartum depression to psychosis but rather based on the degree and severity of intrusive thoughts and hallucinations – the degree of psychotic symptoms may very well determine and drive the ‘depression.’ Additional research will tell if this is the case.

Addendum

Phase II of this study, a follow up confirmatory factor analysis was begun, some data collected (n=100), but not completed. When the economy tanked in 2008-9, I, and many other adjunct faculty were let go. I hope to resume this research soon through Hormones Matter.

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Do I Have Postpartum Depression? Case Scenario and Resources

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Postpartum depression may occur in up to 1 of every 8 pregnant women. Here, we produce a fictional representation of how it may present to you in real life, whether you are a family member, friend, or spouse. It is important to note that postpartum depression can also occur during pregnancy, and can occur as a seemingly ‘normal’ event of childbirth depression, yet postpartum depression carries more burdens and feelings of being totally overwhelmed, less in control of one’s life, anger, and rage. Gradiations of postpartum depression thus can be so subtle that you think nothing of it, yet with extreme postpartum depression, the mother is encompassed by hallucinations or voices incessantly talking to her, instructing her to harm herself and/or her child. The number one cause of death in new mothers is suicide, with thoughts of suicide and self-inflicted harm as very serious problems (Moses-Koldo, 2009; Lindahl, 2005)

Recognizing Postpartum Depression: A Case Scenario

Her name was Anna, little Anna. She soundly slept in the car all the way home, as if she was going to be a “good baby.” Her little hands scrunched up into balls every so often, and although she slept, her eyes moved just so, proving that she was in rapid eye movement sleep.

In the front seat, the mother with the straggly hair, Josephina, put on the smiling face of a clown. None of the doctors had noticed a thing that was wrong with her, even though she did complain to one good-looking young doctor in training. All he did was scoff at her. He made her feel ashamed and silly. But inwardly, she was petrified, just petrified, of being left alone with this little being that depended on her for everything.  Her thoughts of throwing the baby off the ledge and jumping in after her, like diving into a pool, continued to grow in their intensity, frequency, and enormity.  Josephine was scared to turn the lock and enter back into her apartment that represented loneliness, so she let her friend Marissa do it. Marissa stayed long enough to lay the baby in a clothes drawer on the floor, surrounded by blankets so soft that they still smelled like fabric softener.

As Josephine said her goodbyes and closed the front door with barely a squeak, she silently turned her back onto the white painted door. Slowly, ever so slowly, she slid down the door crying silent yet violent tears, body heaving, until at last she was sitting on the floor. All the thoughts continued to pound in her head: “Throw the baby out the balcony! Jump in and just dive in after her!” Her unkempt hands held her head, fighting the increasing enormity of the battle. “Do it!” “Do it!” Josephine grasped aloud at these intrusive thoughts that didn’t belong in her brain. She knew they didn’t belong there, and she felt cursed upon realizing what an ungrateful new mother she must be. Maybe she didn’t deserve to have this little Anna at all. Laden with guilt, she rocked herself on the floor and thankfully, the baby slept through it all.

She thought, as she wiped her tears for the millionth time, “Do all mothers feel this way? Do they all go through this? Aren’t I supposed to be happy?” Of course she was tired. No, she was exhausted. Of course she had continuing insomnia and her mood swings were unpredictable and covered the expanse of linear possibilities: one minute laughing and the next minute, crying. She looked at her hands and they were trembling as another layer of guilt fell over her like a black sheet at Halloween, showing only her eyes. She ran to the bathroom and threw up for the third day in a row. The thoughts turned into guilt and shame, chastising her very soul. She should be happy, but she wasn’t. She should be having happy thoughts, but she wasn’t. Another black sheet of guilt and remorse fell upon her, and her shoulders drooped with the heavy weight that she bore. She wanted to scream! She wanted to run! And yes! She wanted to jump over that balcony!

The exhaustion, insomnia, and the overwhelming state of mind were perfectly normal for any new or seasoned mother, indeed. Each pregnancy was different, but all pregnancies carry with them the dawning of another layer of new responsibilities, the screaming of a helpless being, the bursting of the mother’s eardrums, a hundredfold changes in circulating hormones, and concurrent inflammatory reactions that all but wreak havoc on a woman’s body. If she also suffers from poor nutritional status, this further compounds the biochemical reactions in her body, adding another twist of lime. When the baby cries, the breasts drip milk; it’s just automatic. Her body is a robotic machine, connected inexplicably to her baby, just as if the umbilical cord had never been cut. Mother and child are still tied together. Like a parasite of alien proportions, the baby sucks at her breasts and also sucks at her life.

Transition to Motherhood: When Postpartum Depression Rears its Ugly Head

For most women, this depression hits its worst on the day of the “Third Day” blues. Then it seemingly disappears just as quickly as it came. The blues gently fade away with day number four; they can last a week or two. Mom is smiling and laughing again. She has no thought of harm to herself or her baby.

Risk factors and symptoms for postpartum depression are broad and ill-defined. Some research focuses on the sadness, the lack of energy and the depression, while other research suggests postpartum depression is not really a depression in the classic sense, but an anxious feeling of unease, marked by increased intrusive thoughts, like those Josephina experienced. In truth, how and when women present with postpartum depression is highly variable. The symptoms can begin in pregnancy, 3-6 weeks after childbirth, or really anytime. For more information about pregnancy and postpartum psychiatric distress, the following articles may be helpful: Framing the Pregnancy Postpartum Hormone Mood Debate, Beyond Depression: Understanding Perinatal Mental Health,  Maternal Psychiatric Disturbances and Hormones, What Causes Postpartum Depression? You might also consider reading the personal stories listed on our blog about postpartum depression. If someone you know is suffering from postpartum depression after childbirth and you reach out, you may save a life.

Reaching Out to a Postpartum Woman

So you are the one that had met Josephina in the market before she had her baby, and you exchanged phone numbers with her. You are new in town, live comfortably with your husband and two toddlers, and are looking for a friend. You want another baby, but your husband does not. You decide to call Josephina to see how she is doing.

“Hi Josephina. This is Elena. Remember we met in the grocery store? My kids and I were wondering if we can stop by and visit. We have a gift for you and the baby. Call us back when you can, ok?” You leave a message on her cell phone, as Josephina did not pick up. She was too busy staring at the floor, feeling too sad and guilty to move.

You call her again the next day, after Josephina had awakened in a sweaty bed, had only two hours of sleep, and felt like a walking zombie. This time, Josephina picked up the phone and said you could come visit.

You and your children arrived to her apartment door knowing that it was the right one; you could hear the screaming baby all the way down the hallway. You, being so perceptive, also noted that you could not hear any words of consolation, no kisses, no whispers or singing of lullabies. Josephina answered the door, walking away without saying hello. She mumbled something about going to get the baby, and came back from the bedroom with little Anna. You let your children play with the baby laying in her portable car seat, while you pulled Josephina aside.

“What’s wrong, honey? You don’t look so good to me.” Clearly, Josephina was sorely depressed and had not yet bonded with her baby. She was thin as a rail, malnourished, unkempt to the extreme, and you sought immediate help for a diagnosis of Postpartum Depression. You told Josephina to go take a nice bath or shower, put on some clean clothes, and by the time she was finished, you would have a few phone numbers for her to call, a few resources for her to use so that she could get help and not be all alone with this beautiful baby girl.

Josephina stood still. She was catatonic. Immobilized. So you turned on the shower, took away the razor blades on the tub, and got her undressed. You went back and forth, checking on the baby, looking for baby formula, and watching Josephina shower. “Put the shampoo on first, Josephina.” You got internet access on your iPhone and did a search for Postpartum Depression. Finding a page full of resources, you checked on the baby and the children, then on Josephina again, saying, “Okay, Josephina, time to do shampoo number two!”

And you started making phone calls. You learned that Postpartum Depression is the #1 complication of childbirth. 1 in 8 women suffer from Postpartum Depression (that we know of), many going undiagnosed.

Approaches to Postpartum Depression

Treating postpartum depression presents unique challenges and concerns compared to treating depression or other mental health issues in non-pregnant women. In addition to the concerns about breastfeeding, new moms are sleep-deprived, sometimes feel isolated, have just undergone enormous hormonal changes and are often nutritionally deficient. Tackling these issues may require multiple treatment modalities. Here is an overview of the standard approaches to postpartum depression treatment.

  1. Counseling/Psychosocial Assessment and Support. This first-line road to better mental health helps with talking about your thoughts, coping mechanisms, and problem-solving; removal of solitude can make a huge difference. In addition to individual therapy, a number of postpartum and parenting support groups exist in every community, and many referral systems are in place through helpline resources, such as Resources International “Get Help”  http://www.postpartum.net/Get-Help.aspx .
  2. Anti-depressants, anxiolytics and/or other medications.  A common method to treat postpartum depression, but it is not without controversy and risk. If you are breastfeeding, be sure and talk to your doctor about which drug(s) to go on. Medications may pass from the mother through breast milk to the baby. It is crucial to note that with adolescents and young adults and postpartum women some antidepressants may lead to “…increased risk of suicidal thinking and behavior…” exacerbating the situation. (NIH; Package Insert). You may want to seek at least two opinions before starting antidepressant therapy.
  3. Hormone therapy. Still an area of controversy, some clinicians advocate attenuating the decrease in postpartum estradiol with transdermal estradiol (Moses-Kolo, 2009). The thinking is that if this hormone declines more gradually over time, the symptoms of postpartum depression may lessen or diminish completely. The research is mixed. Other research suggests declines in progesterone are linked to symptoms and thus, treating with progesterone may alleviate the symptoms. (It should be noted, however, that synthetic progesterone as is found in birth control pills, exacerbates postpartum depressive symptoms and should be avoided.) And yet, other research suggests that it is not the decline in estrogens or progesterone that spur postpartum symptoms, but rather abnormal fluxes in androgen hormones. It should be noted that undiagnosed thyroid conditions are common in women, especially during pregnancy and following childbirth, and so, thyroid disease might also be responsible for the onset of symptoms. With postpartum psychiatric issues, thyroid disease should always be tested for and treated if found, ideally prior to beginning other therapeutic interventions.
  4. Ongoing NIH Clinical Trial: If you are interested in participating in a clinical study on mood changes after childbirth whether or not you have had postpartum depression before, you can visit the NIH website here. This Screening Program to Evaluate Women with Postpartum-related Mood and Behavioral Disorders (Study 03-M-0138) is currently recruiting volunteers. Selected patients may be asked to participate in a follow-up study using estradiol for postpartum depression.
  5. Nutritional therapy. Emerging evidence connects nutritional deficits to postpartum psychiatric symptoms. With the added physical burden of pregnancy and childbirth, previously hidden nutritional deficits become unmasked and can initiate a cascade of psychiatric and inflammatory reactions.

From Postpartum Depression to Psychosis

“Put on your conditioner now, Josephina,” you instruct, as you sit and make some phone calls. Even your own hands are shaking now, because you don’t want her to lose her baby to the State, but you also don’t want her to take her baby and jump off the balcony. By this time, she has told you everything. It is almost too much. You are overwhelmed and you know that she needs professional help. You know that the next 15 minutes will be crucial, even staggering, in how you approach her illness. Your concern for how this will impact the rest of her life almost leaves you frozen, but you know that you know that you know that two lives hinge on your decisions. And to further confound matters, you know that none of your options will be optimal. No matter which path you choose, you could be perceived as ‘the bad guy’. The diagnosis may be made, but the treatment options are limited and wrought with controversy. There is no easy answer. Every choice comes with a consequence and you can only do your best.

Frightened at the unknown future results of your own actions, you begin to doubt yourself as pessimistic thoughts cry out: “What if I make the wrong decision?” You oscillate between worries, “If I do nothing and she hurts herself, it would be my fault.” On the other hand, “But if I call 911 and they take the baby from her, I would have to live knowing that I did that to her and the baby.” Back and forth you go. The reasonable, pragmatic side of you knows for a fact that Josephina can not take care of herself and can not be left alone with her baby. For one moment, the squeals of the baby break through the coo’s of your own children’s laughter, almost as a reminder, say yes! It is a reminder of how things are ‘supposed’ to be. Again, you internalize this conclusion, knowing that you need help yourself. You cannot bear this burden alone. You have no experience with this, you dread making a life-long or fatal mistake. You are smothered into a corner to do something NOW!

So you decide to call for help.

When Postpartum Depression Becomes an Emergency: Finding Help

Debating psychotic disorders and parenting, and the relevance of a mother’s children for general adult psychiatric services was, in 2000, Louise Howard’s project as a Research Fellow. She stated that women with psychiatric issues who become pregnant should be specifically identified for further study, assessment, and improved outcomes, considering their children. The impact of the parent’s illness on the children, as well as a need for supportive services, needed further study.

In 2000 in the UK, a woman could voluntarily admit herself to a the first psychiatric unit, the first women-only residential mental health crisis unit in Drayton Park, North London, where children could be admitted with their mothers (Killaspy, 2000).  Residential alternatives to inpatient ward care in England have since been shown to provide more patient autonomy, greater satisfaction, less coercion, more ‘voice’, less aggression, and less anger (Osborn, 2010). Since the 1980’s, these residential units have been rampant throughout the Australia, UK, Europe, and New Zealand.

In the USA, there are many ‘postpartum depression treatment centers’ that can serve as the initial call for help, and provide care in the outpatient clinic setting. This resource seems most appropriate for women with depression who are not hysterical, hallucinating, are overcome by intrusive thoughts, or are having visions or hearing voices. For a government department (i.e., Substance Abuse and Mental Health Services, or SAMHSA) that is continually updated and offers local, mental health referrals, use telephone 1-800-662-4357, 1-800-662-HELP, and/or website www.findtreatment.samhsa.gov .

During the week of August 11, 2011, the U.S.’s first treatment center based on the Drayton Park, London model of inpatient mother:child care opened. This was first inpatient facility for severe postpartum depression for both mothers and babies. It is still located at the University of North Carolina’s Chapel Hill hospital’s psychiatric ward. Brown’s University has a Postpartum Day Hospital opened for mothers and their baby’s weekdays from 9 am to 5 pm (Stampler, 2011).

A bipolar woman who gets pregnant has an increased chance of having postpartum depression leading to postpartum psychosis (Marks, 1992), but she may not seek care for her needs, for fear that her baby will be taken away from her (Howard 2000). When things have escalated to the point of Mom wanting to harm herself or the baby because of voices in her teeth telling her to do so, psychosis may exist and this demands immediate emergency care. Society still places a stigma on mental illness and it is unfortunate that an involuntary admission to a psychiatric unit is usually accompanied with separation from the child(ren).

In the United States, the most common route is for the woman to be rather forcefully taken by the police to determine her fate in jail or a psychiatric ward. Nonetheless, you must call 911 for any immediate danger to self or baby. When you do, a number of things may happen depending upon the state that you reside in.

As a useful tool to help you assess whether or not you have severe postpartum depression, Harvard Medial School’s “Edinburgh Postnatal Depression Scale” is an online test you can take in 5 minutes.

From Bad to Worse: When Postpartum Depression Risks Harming the Mom and Baby

Poor Josephina cannot dress herself. So you help, frequently checking on the baby and your own children who are happily playing in the living room. You ask Josephina several questions, “Do you have anyone to help you with the baby? Any relatives here?” Josephina just nods her head, “No.”  As you continue to help her get dressed, you ask her if she’s taking any medications. “No.” You ask her if she is still having these thoughts of jumping off the balcony and she slowly nods her head, “Yes” as her eyes widen and her eyes turn maliciously toward yours. “Get her away from me. Take her now. Please take her now and take care of her. I can’t take care of her. I beg you to please take her.”

You are in shock as you make her write it down on a piece of paper, dated and signed with her signature. You only left her for 15 seconds to check on the children, but already she had bolted with the car seat and the baby, and was trying to unlock the sliding glass door. You turn to Jimmy, the older boy and look him in the eyes. “Call 911 now.” He’s not sure why, but he can tell Mommy is in no mood for questions. As he picks up the phone, Josephina and Elena fight at the sliding glass door lock, each trying their own destination: Josephina to open it, and Elena to close it. The baby is suspended in mid-air and Elena says, “Put the baby down! Put the baby down now!” Josephina looks like a maniac now, bloodying up her fingernails on the door latch in a desperate attempt to jump off the balcony. They both hear, “Um. I’m not sure, but my Mom and a lady are fighting over a baby at the balcony.”

The little child of Elena, Cristal, starts crying. Mommy said, “Go and lock yourselves in the bathroom. Here, take the baby with you.” And in one final attempt and with all her bloody might, Elena kicked Josephina enough to sidetrack her for a microsecond. Elena forced the baby car seat out of Josephina’s grasp, and ran with all three children to the bathroom. As she turned the corner, she could see that Josephina was staring at her bloody fingernails, then looked up at her, then began to dart for the bathroom door. Elena got all the children in, and told Jimmy to lock the door. Now, the children were safe.

This 1 in 10,000 chance of a psychotic depression has turned into a police matter now, and Elena poses. She is ready to fight for all the babies. But she speaks in a calm tone, reminds Josephina of the calm shower, and gets her to sit down. Shortly thereafter, the police are at the door and they take Josephina away to book her for Child Endangerment and Danger to Self.

It’s not Josephina’s fault that her psychosis led her to this. If one person had listened to her earlier, she would have received help earlier, and this never would have happened. If she had known, she could have voluntarily turned herself in to a postpartum treatment center. If she had known, she could have taken the Edinburgh Postnatal Depression Scale test on her own, to self-diagnose and self-realize the extent of her own depression. If only…

But there is no pity for her, no blaming the biochemical changes in her brain, much like that described in people with a brain tumor who do aggressive things without realizing it. She is ostracized as a criminal instead of as a psychiatric patient, and is sentenced to 15 years in a Woman’s Prison. Being as there are no relatives that come forward, Elena gains first temporary and then permanent Custody of little Anna, then moves away to another city. Not something she had planned at that first chance meeting in the store.

If Josephina gets a proper diagnosis, showing that she was bipolar before the pregnancy, and receives proper treatment, her chances of recovery are 100%. But there’s a catch. She may never be able to go off her medications.

To learn more about resources for postpartum depression: Resources for Postpartum Depression.

About the Author: Dr. Margaret Aranda is a USC medical school graduate, as well as an anesthesiology resident and critical care Fellow graduate of Stanford. After a tragic car accident in 2006, she unfolded her passion of writing to advance the cause of health and wellness for girls and women. You can read more of her work on her personal blog, Dr. Margaret Aranda, her Pinterest page, a page on Postpartum Depression, her author’s page at Tate Publishing or follow Dr. Aranda on twitter @DrM_ArandaMD.

References

  1. Howard, L. Psychotic disorders and parenting – the relevance of parents’ children for general adult psychiatric services. Psych Bull 2000; 24:324-326. http://pb.rcpsych.org/content/24/9/324.full (Accessed June 26, 2014).
  2. Killaspy, H., et al. Drayton Park, an alternative to hospital admission for women in acute mental crisis. Psychiatric Bulletin, 24, 101- 104. Abstract/FREE Full Text
  3. Lindahl, V., et al. Prevalence of suicidality during pregnancy and postpartum. Arch Womens Ment Health. 2005 Jun;8(2):77-87. Epub 2005 May 11. http://www.ncbi.nlm.nih.gov/pubmed/15883651 (Accessed June 26, 2014).
  4. Marks,  M.N., et. al. Contribution of psychological and social factors to psychotic and non-psychotic relapse after childbirth in women with previous histories of affective disorder. J Affect Disord, 1992: 29, 253-264.
  5. Moses-Kolo, E.L., et.al. Transdermal estradiol for postpartum depression: A promising treatment option.  Clin Obstet Gynecol.  Sep 2009; 52(3): 516-529. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782667/ (Accesed June 26, 2014).
  6. NIH. Transforming the understanding and treatment of mental illnesses. Depression. FDA Warning on Antidepressants. 2011. http://www.nimh.nih.gov/health/publications/depression/index.shtml. (Accessed June 26, 2014).
  7. Osborn, P.J., et. al. Residential alternatives to acute in-patient care in England: satisfaction, ward atmosphere, and service user experiences. Br J Psych 2010: 197:x41-s45. http://bjp.rcpsych.org/content/197/Supplement_53/s41.full (Accessed June 26, 2014).
  8. Package Insert. Fluoxetine hydrochloride. 1987. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018936s091lbl.pdf (Accessed June 26, 2014).
  9. Stampler, S. First U.S. Inpatient Clinic for Moms with PostPartum Depression Opens. Huffington Post: Parents. Oct 19, 2011. http://www.huffingtonpost.com/2011/08/19/americas-first-inpatient-postpartum-depression-unit_n_931179.html (Accessed June 27, 2014).
  10. Treatment Centers. Study examines postpartum depression. Psychiatry/Mental Health. May 24, 2010. http://www.treatmentcenters.net/psychiatry-mental-health/study-examines-postpartum-depression/ (Accessed June 27, 2014).
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Maternal Psychiatric Disturbances and Hormones

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As a mom of young children, I was very much affected by the Andrea Yates case. If you recall she experienced successive bouts of psychosis and pursued multiple attempts at suicide following the delivery of each of her children. After her fifth child, she drowned her children, killing them all. The case was a heartbreaking, and I believe, a totally preventable tragedy had her psychosis been taken seriously by medical professionals, family and others in the community. In spite of her psychosis and suicide attempts she was sent home to care for her children, as if a woman with postpartum psychosis is somehow less ill than a man or than a woman whose psychosis develops unrelated to her pregnancies. Raising young children is difficult, even under the best of circumstances, but sending a severely depressed and psychotic woman home to care for young children is just downright negligent. Although there was blame to go around among the doctors, her family and community, I couldn’t but shake the feeling that this tragedy could have been averted if her illness had been taken more seriously.

Identifying the Biological Underpinnings of Maternal Psychiatric Disturbances

The Andrea Yates tragedy inspired me to research and identify the clinical and biological components of perinatal mental illness. My goal was to identify early warning markers; biological tests, that would give women, their physicians and family members a way to predict the possibility of illness and confirm that illness once it had arrived. I thought that if we could predict and identify the risk for this illness, then the families could prepare and maybe even lessen the severity the disease process. At the very least, tragedies like the Andrea Yates case could be prevented.

I knew hormones would be key to the onset and maintenance of perinatal psychiatric symptoms. What I didn’t know is which hormones, when, and related to which symptoms. It seems that no one else did either. Despite years of research and a clear temporal association between the onset of psychiatric distress and childbirth, only tenuous connections between maternal hormone concentrations and varying degrees of postpartum depression had ever been established. This was primarily because the research was focused so narrowly upon the relationships among what are often referred to as the female hormones, progesterone and estradiol, and depressive symptoms. Very little research had examined associations between a broader range of steroid hormones and the full spectrum of potential psychiatric symptoms. This didn’t make sense to me. Certainly, other hormones affected by pregnancy, might also impact brain chemistry; certainly, the range of clinical symptoms that women might experience would go beyond the blues and depression. Even when psychosis appeared, I wasn’t convinced that the psychosis of pregnancy and postpartum was clinically similar to the psychoses that developed irrespective of the vast biochemical changes that took place across pregnancy, parturition and in the weeks and months that followed. If the biochemistry was different, as it most necessarily had to be, wouldn’t everything else about maternal psychiatric disturbances be different as well?

Looking Beyond the Boundaries

And so began my research. For the first study: Beyond Progesterone and Estrogen: Maternal Psychiatric Disturbances Linked to Adrenal Androgens, I recruited healthy, medication free, first time moms, with no previous history of mental illness. This was no easy feat. I soon realized that many women, even pregnant women, were using antidepressants and anxiolytics and many other medications. It seems the old adage that pregnant women should not take medications lest it cross the placental barrier and affect the developing fetus, had fallen by the wayside.

To assess the psychiatric distress, I abandoned the singular blues, depression and anxiety scales used so often in this research and found a broad-based, standardized assessment of psychiatric distress called the Symptom Check List 90R (SCL90R). SCL-90R is a 90-item psychiatric self-report inventory designed to measure the severity and intensity of psychiatric symptoms in both inpatient and outpatient populations. Participants rate the severity of distress experienced during the prior seven-day period using a 0-4 Likert-type scale (0=no distress-“not at all” to 4=extreme). Symptoms measured included: anxiety, hostility (aggression, irritability, etc.) phobic anxiety, paranoid ideation, psychoticism, somatization (perceptions of pain or other physical disturbances), obsessive-compulsive behavior, interpersonal sensitivity (feelings of personal inadequacy), depression and the global severity index (GSI), which reflects the overall symptom severity.

Along with the clinical symptoms, I measured five hormones, progesterone, DHEAS, testosterone, estrone, estradiol and estradiol, using saliva based testing. Symptoms and hormones were assessed twice, first in late pregnancy at 37 weeks (n =32) and again within 10 days following the delivery of their children (n=28, four were lost to attrition). I also conducted a year long follow up of those same participants and will report those data soon.

It’s Not Just Depression and It’s Not Just Postpartum

As I suspected, symptoms were present in late pregnancy and in some cases, increased in severity postpartum, but in other cases, decreased in severity. For some women, pregnancy was more problematic than postpartum, especially those with obsessive compulsive symptoms.

Fully 50% of the women tested experienced symptoms during pregnancy and 57% postpartum. This means maternal psychiatric distress is far more common than generally ascribed. As a group the anxiety related symptom scales, particularly the anxiety and obsessive compulsive scales, had the highest individual scores at each test time and when combined with hostility, phobia and psychoticism contributed the largest increase in symptom severity from pregnancy to postpartum. So it wasn’t the blues and depressive type symptoms that were most troubling, but the agitated, anxiety and even psychotic type symptoms that were the most severe.

Current research suggests that for only 1-2 per 1000 pregnancies psychosis will develop. What I found with this research and from another study,  is that psychotic symptoms were far more prevalent than recognized and may be the symptoms that drive the depression. In this study, we found sub-threshold, but clinically relevant, psychotic symptoms present in several of the women postpartum. Their symptoms were absent concurrent elevations in paranoia (paranoia and psychosis often go hand in hand). The most frequently ascribed to symptoms within this cluster included fears of serious illness (n=8), loss of mind (n=7) and isolation (n=12). Surprisingly, three women showed mild to moderate distress about thought insertion and thought broadcasting, two were concerned about thought control and one woman indicated distress about auditory hallucinations. Interestingly, it was these very same women who had the most dysregulated hormone profiles.

In speaking with the women who indicated these symptoms, the visual hallucinations, involved their children suffering; usually graphic intrusive thoughts, seeing images of their children being burned, thrown out windows, cut with a butcher knife, strangled with the breast pump tubing and the like. When auditory hallucinations were present they berated the women for their weakness, bad mothering etc., inducing guilt and one can only assume, depression. We confirmed the prevalence of these types of symptoms in two subsequent studies, the first published here: Dimensions of postpartum psychiatric distress: preliminary evidence for broadening clinical scope, the second unpublished as of yet.

Aberrant  Androgen Metabolism may be to Blame for Maternal Psychiatric Symptoms

As I suspected and as much research had shown, no symptom clusters were correlated with progesterone, estrone or estriol either pre- or postpartum.  While expected to be a close correlate of postpartum psychiatric symptoms, estradiol was associated with very few symptom clusters in the present study. Instead, it was the androgens that were linked to the symptoms at both time periods and not in a way that might be expected.

Low late pregnancy testosterone was not only related to late pregnancy psychiatric symptoms, but significantly predicted postpartum symptom severity. In conjunction, and this is where the endocrinology gets interesting, elevated late pregnancy DHEAS and supra-elevated postpartum DHEAS were associated with pre – and postpartum symptoms, respectively. This was exciting, because in theory these two hormones should not be aligned. That is, high DHEAS should correlate with high testosterone and it didn’t. So somewhere between DHEAS>DHEA>androstenedione> testosterone there was a problem and I had pretty good idea where.

For now though, we had a pilot study that ripped open the notions that maternal psychiatric distress occurred only during postpartum, was depressive in nature, was rare and was related to the normal or expected hormone changes of pregnancy. It was none of these things. The psychiatric distress was present at both test points, was more agitated, included a spectrum of symptoms, and most importantly, was related to aberrant changes in hormones that were likely exacerbated by the normal or expected hormone disruptions of pregnancy.  I was very excited. If we could identify the problem, then we could fix it right?

Not so fast. I could never get the research published and though I carried on with research I could do without funding, including a long term follow-up of the same participants (to be self-published soon) and an online study of the symptoms of psychiatric distress, the hormone work was routinely and summarily rejected. I learned very quickly how controversial studying hormones in women’s health was. So there it stands, the work was good, it pointed to a biomarker that could be used to identify and then treat a group of women who suffer horribly, but the study needs to be replicated with a much larger and more diverse population of women. It is likely that this is but one of many potential markers along this hormone pathway that could be used to predict and prevent perinatal psychiatric distress. It is also likely that this pattern of metabolism is linked to a host of other mental health and physical health issues. It was because of this research that I began Hormones Matter and have worked so arduously to increase awareness about the need for more research in women’s health. Hormones ought to be measured consistently across a woman’s life span, they aren’t and we need to change that.

Here are the full study details and the article, now officially self-published: Beyond Progesterone and Estrogen: Maternal Psychiatric Disturbances Linked to Adrenal Androgens.

Another portion of this study included assessing cognitive changes: Mommy Brain: Pregnancy and Postpartum Memory Deficits.

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Framing the Pregnancy Postpartum Hormone Mood Debate

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The two years beginning in late pregnancy and continuing post childbirth can be particularly difficult for many women. The risk of serious mental illness is significantly higher than at any other time in a woman’s life. More often than not, however, the mental health issues are attributed to the stress of becoming a mom and though hormones are often in the mix, the consensus about pregnancy and postpartum hormone-related mental health changes is more broad than specific, anecdotal than evidence based. The prevailing hypothesis suggests that puerperal mental illness, commonly referred to and investigated as postpartum depression, is not the result of endocrine pathophysiology, but rather a ‘maladaptive’ response to normal changes in reproductive hormones.  In other words, having babies is a normal function, with normal hormone changes, ‘if you can’t handle it, there must be something wrong with you.’

The fact that there are no norms or even broad reference ranges established for pregnancy/postpartum hormone changes doesn’t seem to enter into many conversations (how can one reasonably say something is normal if it isn’t ever measured?); nor does the fact that ‘abnormal’ hormone changes could easily be causative in mental illness or the fact that ‘normal’ hormone changes, if large enough, such as during pregnancy and following childbirth are likely to impact mood, cognition and behavior in some fairly noticeable ways. Failing to recognize and prepare women and their families for the spectrum of the biochemically mediated  mental health or mental status changes, whether they are ’normal’ or not, is just wrong and potentially dangerous. Many years ago, I set out to change that – to understand how the hormones of pregnancy and postpartum could affect mental health and cognition. What I found was fascinating, but first, a little (OK, a lot of) background.

Fundamental Precepts about Hormones and Behavior

All of my research begins with the basic proposition that hormones affect brain chemistry. We know from animal research that hormone receptors are located all over the brain (and the body for that matter), even in areas not responsible for reproduction. We also know that steroid hormones produced in the body, because they are lipid soluble, easily cross the blood-brain-barrier and bind to hormone and non-hormone receptors to change brain chemistry. And, we know that the brain can and does produce a full complement of steroid hormones by itself, having all of the necessary building blocks to synthesize hormones de novo or from scratch. Since the brain is the control center for mental health, cognition and indeed, everything, it stands to reason that because hormone activity is integral to brain chemistry, hormones are involved in mental health. Indeed, there are no biologically or even logically plausible reasons to remove hormones from any discussion of brain chemistry or subsequent changes in mental status. It just makes no sense.

Pregnancy and Postpartum Hormone Changes Mirror an Addiction Withdrawal Cycle

We see hints, sometimes rather loud hints, of the hormone-brain connection across a woman’s life cycle (puberty and menopause) and across the menstrual cycle, but these are often more gradual and less drastic biochemical changes than those of pregnancy and postpartum. During pregnancy, some hormones increase by over 1000 times their non-pregnant concentrations, only to drop immediately, to nothing or almost nothing following childbirth. Simultaneously, other hormones seem to increase following childbirth, thus, creating the complex chemical cocktail that is postpartum. With these enormous changes in biochemistry, it is truly remarkable that so few women experience difficulties.

From a pharmacological standpoint, the hormone changes across pregnancy and postpartum provide the perfect drug addiction-withdrawal model, where the drug use increases gradually but significantly over an extended period of time only to be eliminated cold turkey over a period of a couple days. From the brain’s standpoint, while there may be differences in specific reactions, there really is no difference, broadly speaking, between compensatory reactions it exhibits relative to increasing concentrations of a drug followed by its abrupt withdrawal and those it exhibits relative to increasing concentrations of hormones followed by abrupt withdrawal. The brain is going to get used to having certain concentrations of chemicals floating around and adapt accordingly. When those chemicals are removed, especially abruptly, there will be hell to pay in the withdrawal syndrome. How that withdrawal syndrome manifests will be contingent on the degree and pattern of biochemical change – which hormones or drug(s) are creating the problems, where and to what degree.

Consider alcohol versus heroin withdrawal as an example. Both withdrawal periods are horrible, but because each drug acts on different neurotransmitters within the brain, each withdrawal syndrome looks a little bit different. It is the same way with hormones. Each elicits a different biochemical reaction in the brain. Some hormones are sedatives, some are stimulants, some are direct, some are indirect; some have a whole bunch of receptors in areas of the brain that control memory, while others have receptors in the emotional centers of the brain. Without measuring the actual hormone changes associated with pregnancy and postpartum and the behavioral symptoms that ensue, there is no way to recognize or to treat a postpartum withdrawal syndrome or syndromes. And as many of you well know, hormone measurement in women’s health is all but ignored.

Pregnancy and Postpartum Mood Changes are Poorly Characterized

Perhaps because of our feminist tendencies (not wanting to admit that hormones affect our moods or our cognitive abilities), perhaps politics (blaming women) or perhaps just poor research (including that which does not consider the role of hormones in the diagnostic criteria), the standard nomenclature and diagnostic parameters for postpartum mental health issues are at best poorly defined and at worst completely incorrect.

According popular perspectives, the three classes of postpartum disease are the baby blues which is said to affect 80% of all new moms, postpartum depression that develops in 10-15% of women and postpartum psychosis, the rare condition that afflicts 1-2 per 1000 pregnant women. What does this mean? It looks like a progression of sadness that leads to psychosis. Is this what postpartum women experience? Well, not really, but the nomenclature stuck and was sufficiently correct that they could characterize some of the symptoms, in some of the women, to make using these terms a useful shorthand. However, because the symptoms associated with each of these conditions were never fully characterized appropriately, they have been repeatedly included or dis-included from diagnostic manuals with varying and even diametrically opposed diagnostic criteria depending upon the political winds of any given generation (the pitfalls of consensus based medicine).

Indeed, in the last iterations (IV, TR) of the DSM manual (the diagnostic bible for mental illness), postpartum was merely a time course specifier. That means, none of these conditions actually existed according to the diagnostic manual. There was no discrete illness or set of illnesses recognized as unique to the postpartum period, and certainly none connected to postpartum hormone changes.  Depression or psychosis, if they happened to arise within 30 days of childbirth, was considered postpartum related.  If these conditions developed during pregnancy or after the 30 day period, then they were not considered postpartum related. In effect, these conditions were just the normal, run-of-the-mill depression or psychosis.  From a purely logical standpoint, it seems difficult to believe that the brain chemistry of a postpartum woman is in any way similar to the brain chemistry of teenager or menopausal, or other non-postpartum woman or to a male depressed or psychotic patient.  If we believe that brain chemistry mediates behavior (and isn’t the entire medical-pharmaceutical establishment built on that presumption), why would we presume that radically different brain chemistries produce the same symptoms or behaviors?  We wouldn’t.

So, on the one hand, we have popular terminology that has done wonders to bring awareness to the potential difficulties some women have following childbirth but whose terms were not consistent with the DSM criteria. On the other hand, we have DSM criteria that really didn’t recognize postpartum as unique condition, but only as a time-frame to be noted and neither set of diagnostic opportunities was based on evidence that truly considered specific hormones changes might impact brain chemistry. Sure, there has always been the tacit – it’s hormonal – and certainly, there has been hormone-mood research but attempting to delineate which hormones, in which women, relative to which symptoms and within what time frame has yet to be fully addressed. And, as one might imagine, it is difficult to bring another set of variables – hormones- into an already poorly defined disease space. Do we measure hormones related to blues, depression and psychosis or are we measuring something else entirely?

Where to Begin

When beginning a research career in area where the data are limited, one has a few choices – ‘don’t’ -being the first and most logical option; take the safe, career boosting-route of replicating someone else’s work or throw all previous assumptions in the garbage can and begin from scratch. Not being the wisest, of course, I chose the third option.

I had a couple operating assumptions. The first was and still is, that certain hormones affect certain neurotransmitters (we know this to be true from animal research). When we radically change the concentrations of those hormones, the behaviors associated with said neurotransmitters (and maybe even some we hadn’t thought of) would become apparent.  Second, the symptoms that were expressed would be related to the particular pattern of hormone change – whatever that pattern may be. Third, the constellation of symptoms that arose would not likely not fall into the current diagnostic categories, but would cluster together in unique, and yet to be determined, ways. In other words, I believed that certain patterns would emerge based on animal research, but because there was so little human research and much of it was limited in scope, I was prepared for the fact that I was wrong. And I was wrong, in some ways, but that willingness to test more broadly and openly is what led to some pretty amazing discoveries.

How I Think about Perinatal Psychiatric Distress

Last bit of background, I promise. Notice that I said perinatal psychiatric distress and not postpartum depression, mood, or blues. Perinatal psychiatric distress and full-blown psychiatric disorders can emerge during either period, pregnancy or postpartum and relative to a myriad of biochemical and psychosocial factors. Limiting the discussion and nomenclature to ‘postpartum’ ignores women who are affected negatively by the pregnancy hormones and whose symptoms arise prior to delivery of the child.

Similarly, the hormone syndromes are not specifically depressive.  Some of the hormones affected by childbirth are clearly anxiogenic (elicit anxiety) and by the nature of where their receptors are located, other hormones can affect memory, decision-making, impulse control, sensory perception and a wide variety of emotions, physiological and cognitive functions. By categorizing and limiting the syndrome to ‘depression’ even an atypical depression, as it is often referred to, fails to recognize the spectrum or severity of symptoms experienced.

Finally, for the same reasons I don’t use the phrase postpartum depression, I don’t ascribe to the characterization of the baby blues. When one thinks of the baby blues, one immediately thinks of a milder form of depression or sadness. Though useful as a popular term, it does nothing to distinguish what, in some cases, may be emotional expressions of the hormone-based, physiological changes occurring postpartum (or during pregnancy – though not often measured) and in other cases early markers for distress. Neither the term nor the scale used to assess the ‘condition’ has any predictive ability and fails to recognize a whole host of symptoms linked to perinatal hormone changes, that cause significant distress for the mom.

Because there are a myriad of hormones involved in carrying a pregnancy to term that are involved in number of physiological systems, and the symptom expression from those interactions is broad, limiting the focus to depressive type symptoms, unnecessarily limits the spectrum and severity of distress that some women experience.  As with everything, if we don’t measure, we cannot manage. Part of measuring is figuring out what to measure.  Depressive symptoms are certainly important, but they do not represent the totality of the symptoms experienced and so, we must expand the symptom base and re-work the diagnostic nomenclature.

Just Get to the Damned Research, Already!

Why have I spent so much time explaining the nature of postpartum research in general and my assumptions and perspectives specifically?  Why haven’t I just told you what I learned?  Well, because where you start determines where you end up, especially in science. Yes, I could have assumed the definitions and the research supporting those definitions of ‘postpartum depression’ were correct and then designed studies to support the appropriate hypotheses. It certainly would have been easier, but I didn’t. There were too many missing pieces and unanswered questions – things that just didn’t fit or make sense for me to go down that route. I had to create a new path – to throw everything in and let the pieces fall where they may.  I had to let the data tell the story. I did and I will, let the data tell story.

Part two: Beyond Depression, Understanding Perinatal Mental Health.

 

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