Prenatal Infections and Schizophrenia

The etiology of schizophrenia has long been debated and findings have indicated that there are genetic predispositions and family history to consider. Schizophrenia is a debilitating psychiatric disorder that widely impacts about 2-3% of the total adult population (Liu, 2015). Schizophrenia is known to be “without a cure” and patients with schizophrenia may endure lifelong disturbances in their daily living even with consistent use of medication to alleviate the symptoms. There has been expensive research done to assess the prodromal symptoms and etiologies of this disorder in hopes that it will aid in developing preventable measures. However, this blog post will focus in on the research done on the link between prenatal infections and a higher risk of schizophrenia. Recent findings have shown that there are certain gestational infections that increase the risk of schizophrenia in later years (Brown, 2010) due to alteration of brain development. The alternation is believed to cause an increase susceptibility for developing schizophrenia. An increasing number of research shows that there is a significant link between exposure to infections particularly during the first half of the pregnancy term is positively attributed to a higher risk of developing schizophrenia as an adult (Meyer, 2007).

The focus for these research studies was done on patients who were right on the age cutoff for an appropriate adult schizophrenia diagnosis, which is 18 years old. The studies honed in on information for any neurologic complications seen in the patients postnatal, any development delays that were seen, and any other coexisting physiologic or psychiatric disorders. For a majority of these patients, there was a noticeable delay in development in the patients’ younger years. These delays may include cognitive, sitting, standing, walking, speech, and cognitive impairments as well (Liu, 2015). Prenatal exposure to infections have been directly linked in the past to CNS development defects and also to physiological and metabolic diseases (Labouesse, 2015). Research now shows that just as infection in utero may cause an increase in neurologic disorders such as autism, mental retardation and cerebral palsy, it can also be linked to an increase risk for schizophrenia (Labouesse, 2015). It is known that maternal infection can damage critical brain structural development and may cause cognitive functional delays (Brown, 2002). The infection can cause a significant disruption in normal fetal brain development. As children with schizophrenic symptoms have been seen to have a loss of gray matter, increased ventricles, and a decrease in hippocampal size including an overall decrease in brain size, it is safely believed that these neurologic changes were present before the symptoms manifested itself (Brown, 2002). However, research is still being done to determine the exact mechanism in which maternal exposure to infections can cause lasting damage on fetal neurodevelopment.

It is believed that there is a fivefold increase in the risk for schizophrenia based on whether the prenatal infection happened within the first half of the pregnancy (Babulas, 2015). With a longitudinal study done with mothers who had been exposed to herpes simplex virus type 2, there was a positive link to those exposed to the virus in utero developing psychotic symptoms as adults (Buka, 2001). The virus would cross through the placenta and enter the fetal bloodstream, which could then affect neurodevelopment of the fetus. The study followed the postnatal babies and assessed their development and treatment of schizophrenia as gathered from hospital data (Buka, 2001). The study found a positive link between prenatal exposure to herpes simplex type 2 and an increased risk of developing schizophrenia. An older research conducted a longitudinal study on Finnish patients who had been exposed to the influenza epidemic in 1957 (Mednick, 1988). Although there were some holes in the study that have yet to be filled, there was also a positive correlation between the fetus that have been exposed to influenza during the epidemic and a higher number of schizophrenia in the participants of the study. This study also introduced the consideration that those who were born in winter months during which the influenza epidemic was most detrimental were also more likely to develop schizophrenia (Brown, 2002). In this study, however, there was a significant increase of patients with schizophrenia who were specifically exposed during the second-trimester of the pregnancy. This brings to question the importance of the timing of prenatal exposure and what are some preventable measures that can be taken. The more recent research on influenza exposure focuses on diagnostic criteria of influenza rather than focusing on the fetus being in utero during an influenza outbreak (Brown, 2002). Recent research has shown that diagnosed infection while the fetus is in utero has been positively linked to a significant increase (fivefold) in the development of schizophrenia (Brown, 2002).

This topic has many epidemiological implications for ways to consider some preventable measures for prenatal infections. An increase in screening and treatment through antibacterial or antiviral medication would easily solve the problem of infections. Many of these infections go undetected when pregnant women come in for regular checkups and thus would result in lasting neurological effects on the fetus. Due to many infections being treatable or even preventable by antibiotics, it would be a simple cure that may potentially prevent significant neurologic damage and ultimately decrease the risk of developing schizophrenia. It would, first, be crucial that mothers be appropriately diagnosed for any exposure or any infection during their gestational period. Then, treated appropriately so that it will not have lasting effects on fetal neurodevelopment.

 

References

Brown, A. S. and Derkits, E. J. (2010). Prenatal infection and schizophrenia: A review of epidemiologic and translational studies  American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 167, 261-280.

Brown, A. S. and Susser, E. S. (2002), In utero infection and adult schizophrenia. Mental Retardation Developmental Disabilities. Res. Rev., 8: 51–57. doi: 10.1002/mrdd.10004

Buka, S. L., Tsuang, M. T., Torrey, E. F., Klebanoff, M. A., Bernstein, D., Yolken, R. H. (2001). Maternal infections and subsequent psychosis among offspring. Arch Gen Psychiatry. 58:1032–1037

Labouesse, M. A., Langhans, W., Meyer, U. (2015). Long-term pathological consequences of prenatal infection: Beyond brain disorders. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 309, R1. doi:10.1152/ajpregu.00087.2015

Liu, C. H., Keshavan, M. S., Tronick, E., & Seidman, L. J. (2015). Perinatal risks and childhood premorbid indicators of later psychosis: Next steps for early psychosocial interventions. Schizophrenia Bulletin, 41, 801-816. doi:10.1093/schbul/sbv047

Mednick, S. A., Machon, R. A., Huttunen, M. O., Bonett, D. (1988). Adult schizophrenia following prenatal exposure to an influenza epidemic  . Archives of General Psychiatry, 45, 189-192. doi:10.1001/archpsyc.1988.01800260109013

Meyer U., Yee B. K., Feldon J. The neurodevelopmental impact of prenatal infections at different times of preg- nancy: the earlier the worse? (2007). Neuroscientist;13. 241–56.

 

Frights in the Night: Nightmares, Night Terrors, and the Parasomnias in Between

We have likely all had the experience of waking up in the middle of the night, heart pounding, sweat beading on our skin, sheets damp, mind on high alert, ripped quickly from the scene of a horrifying nightmare back into the reality of our bedroom and “real life.” We quickly realize that the harrowing circumstances we just endured were “only a dream,” though sometimes it takes our bodies and minds time to catch up to this comforting truth; time for our heart rates to stabilize, our breathing to return to normal, a sense of safety to return. This is an all too familiar scenario for most of us and a very normal part of the human experience. Less normal and less common, however, are night terrors (also known as pavor nocturnes).  In night terrors, episodes begin suddenly and sufferers will typically sit upright in bed and display extreme fear and agitation. Usually the episode begins with a scream. Motor activity such as thrashing or flailing is common. The eyes may be open or closed. Sympathetic arousal occurs, activating the “fight or flight” response, as evidenced by tachycardia, flushing and diaphoresis. The person will typically be unable to process external stimuli or receive attempts made to comfort them, and will be difficult to fully arouse. Some will rise from bed or might attempt to run away out of fear (an overlap with sleepwalking), but most stay in place (DiMario & Emery, 1987). The victim usually falls back to sleep within 30 minutes though the average length of an episode is only 30 seconds – 5 minutes (Kotagal, 2009).  The episode is rarely remembered in the morning and most victims wake up feeling refreshed as if their sleep was never interrupted (DiMario & Emery, 1987).

Night terrors fall under the umbrella of sleep arousal disorders which also include sleepwalking, sleeptalking and enuresis. These might also be referred to as parasomnias or NREM sleep disorders. There are two major categories of sleep: rapid eye movement (REM) and non-rapid eye movement (NREM), the latter of which is further divided into four categories defined by changes seen on EEG. Stages 3 and 4 are the deepest sleep states and are also known as slow wave sleep (SWS). People spend the most time in SWS over the first 1/3 of the night so this is when night terrors are most common, particularly around the 2 hour marker into the sleep cycle (DiMario & Emery, 1987). The brain cycles regularly between wakefulness, REM and NREM sleep throughout the average night without a problem. Sleep arousal disorders occur when transitions between these stages are “blurred,” most frequently when cycling between stages 3 and 4 into REM sleep or the awake state (Fleetham & Fleming, 2014). Night terrors can be distinguished from nightmares in several ways. First of all, nightmares occur during REM sleep and show different EEG patterns. If one were to find themselves without a sleep lab handy, they might notice that upon awakening from a nightmare, the subject typically remembers their dream and experiences a fully alert state often followed by a delayed return to sleep. If someone were to arise from a nightmare with a scream, they would become aware of their state of mind and responsive to their environment in a manner not seen in NREM arousal disorders. Furthermore, nightmares are more common in the latter third of the night when people are more likely to be in REM sleep (Kotagal, 2009).

Early studies estimated that around 1-6.5% of the population experiences night terrors (DiMario & Emery, 1987). Later studies produced figures somewhere around 3–15% (Kotagal, 2009).  Studies have identified an average age of onset for night terrors between 3 – 10 years old. Night terrors typically resolve by late childhood or early adolescence. When occurring early in life, they are probably related to genetic and developmental factors (Szelenberger et al., 2005). The persistence or new development of night terrors in adulthood is more rare and significantly associated with underlying psychopathology and stressful life events (Kotagal, 2009).

Theories on the potential causes of night terrors include a genetic predisposition (either via specific gene abnormalities or a genetically determined tendency for deeper sleep, some other unknown central nervous system dysfunction (Szelenberger et al., 2005), or febrile illness (Kales et al., 1979). Several psychological theories assert that night terrors could represent a type of conversion or dissociative disorder; a “rift in the ego’s capacity to control anxiety” (Szelenberger et al., 2005), or a manifestation of separation anxiety disorder (Petit et al., 2007). While a small amount of supporting evidence exists for some of these claims, none have been demonstrated consistently enough to be named a definite cause or precipitating factor. However, it is generally accepted that there is a definite heritability factor for sleep arousal disorders, though genetic factors are probably just a small piece of the puzzle. It is likely that environmental and developmental patterns strongly influence the development of the disorders. The overall picture of risk is likely multi-factorial involving a complicated interplay of a variety of predisposing factors (Kales et al., 1980). Sleep arousal disorders might be worsened or triggered by disruptive environmental factors, either external (such as loud noise or uncomfortable temperature) or internal (such as sleep apnea or other respiratory conditions, GERD or uncontrollable limb movement as in RLS) which activate cortical brain regions typically quiet during sleep. Episodes may also be more likely following periods of prolonged sleep deprivation (Fleetham & Fleming, 2014). EEGs obtained during night terrors may show high amplitude, rhythmic delta or theta activity (Kotagal, 2009).

Typically, night terrors are diagnosed clinically based upon reports from clients and the people who regularly observe them. Due to the unpredictable nature, it is often not practical, cost-effective or necessary to attempt to get a polysomnogram. It is essential to consider other medical differential rule-outs including night-time seizure disorders which can be distinguished from parasomnias based on the clinical picture; i.e. that seizures occur randomly throughout the night (usually several times) and leave the sufferer feeling fatigued the next day. If there is any question, an EEG should be ordered. There is a whole other set of parasomnias which occur during REM sleep including REM sleep behavior disorder which could be predictive of degenerative neurological disorders. Catathrenia, sleep-related enuresis, bruxism, and Status Dissociates are other disorders which may occur at a variety of stages throughout the sleep cycle (Kotagal, 2009).

As previously stated, most children with night terrors will eventually grow out of the disorder so the best treatment is “watchful waiting.” The disorder is usually much harder on parents than it is on the children, who remain essentially oblivious to their condition. Beyond emotional support, the first step should be to assure the patient and family of the benign and self-limiting nature of night terrors (Kotagal, 2009). Some medications have been found to be helpful, including alpha blockers, tricyclic antidepressants, SSRIs, benzodiazepines, anticonvulsants and anticholinergic agents. Cognitive-behavioral therapy with cognitive restructuring, imagery rehearsal, relaxation, hypnosis, desensitization, daytime naps, avoiding exhaustion, and trying anticipatory scheduled awakenings might also be effective in some cases. If the disorder persists into adulthood, treatment of any psychiatric disorders, stress management, and abstinence from drugs and alcohol are also recommended (Attarian, 2010). The biggest consideration must always be safety, especially for anyone who experiences sleepwalking along with night terrors in which case child-proofing door handles and installing door alarms would be one safety intervention to consider (Kotagal, 2009).

Night terrors have been referenced as far back as the bible and Shakespeare and attributed to everything from hysteria to supernatural events (Szelenberger et al., 2005). A recent look back through film finds night terrors discussed in a variety of popular horror flicks. It is no wonder why this bizarre and poorly understood disorder captures the imagination of so many, and plays into the deep curiosity and sometimes even fear that so many of us experience surrounding sleep, spirituality and altered levels of consciousness. Until we learn more about the complexities of sleep, there remains a great deal of wiggle room for interpretation and fantastical portrayals of those 6-8 hours we all spend “offline” each night and the memories of internal chaos we may or may not wake up with each morning.

References

Attarian, H. (2010). Treatment options for parasomnias. Neurol Clin., 28(4), 1089-1096. doi:doi: 10.1016/j.ncl.2010.03.025.

DiMario, F., & Emery, S. (1987). The Natural History of Night Terrors.Clinical Pediatrics, 26(10), 505-511. doi:10.1177/000992288702601002.

Fleetham, J., & Fleming, J. (2014). Parasomnias. CMAJ, 186(8). doi:10.1503/cmaj.120808.

Kales, J., Kales, A., Soldatos, C., Chamberlin, K., & Martin, E. (1979). Sleepwalking and night terrors related to febrile illness. Am J Psychiatry,136(9), 1214-1215. Retrieved November 5, 2015, from http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.464.3398&rep=rep1&type=pdf.

Kales, A., Soldatos, C., Bixler, E., Ladda, R., Charney, D., Weber, G., & Schweitzer, P. (1980). Hereditary factors in sleepwalking and night terrors. The British Journal of Psychiatry, 137, 111-118. doi:10.1192/bjp.137.2.111.

Kotagal, S. (2009). Parasomnias in childhood. Sleep Medicine Reviews,13(2), 157-168. doi:10.1016/j.smrv.2008.09.005.

Petit, D., Touchette, E., Tremblay, R., Boivin, M., & Montplaisir, J. (2007). Dyssomnias and Parasomnias in Early Childhood. Pediatrics, 119(5). Retrieved November 7, 2015, from http://pediatrics.aappublications.org/content/119/5/e1016.full.

Szelenberger, W., Niemcewicz, S., & DĄbrowska, A. (2005). Sleepwalking and night terrors: Psychopathological and psychophysiological correlates. International Review of Psychiatry, 17(4), 263-270. doi: 10.1080/09540260500104573.

Sleep on it? Maybe not.

Food, water, sleep – inarguably these are the essentials of life. Sleep has been described as a homeostatic drive that enables us to develop optimally, conserve energy, and consolidate memories, thoughts and experiences (Higgins & George, 2013). Because of the importance of sleep, it has been the subject of extensive research. Sleep is reported on in the health section any online news source on a seemingly daily basis– Are we getting enough or too much sleep? Are we sleeping correctly? How can we improve our sleep? We spend approximately one third of our lives asleep, yet it is shocking how little is still known about what is actually occurring while we are in the state of suspended consciousness that is sleep (Higgins & George, 2013).

Having spent the majority of my life in school, I have been told countless times that getting a good night’s sleep prior to a test outweighs the benefits of staying up late to get those few extra hours of studying. The exact physiology behind memory consolidation during sleep has been studied for over 80 years; however, a consensus has yet to be reached (Higgins & George, 2013). Recently, researchers have begun to make strides towards understanding the process behind sleep dependent memory storage.

Evidence is increasingly showing that thalamocortical slow oscillations, thalamocortical sleep spindles, and hippocampal sharp wave ripples during non-rapid eye movement sleep are what support and facilitate memory consolidation (Goerke, Müller & Cohrs, 2015). It is thought that through these mechanisms, memories are reactivated and transferred from the hippocampus to the necortical region of our brain while we sleep (Goerke, Müller & Cohrs, 2015). This concept of reactivation of memories during sleep is not new. Nearly two decades ago Pierre Maquet et al. used functional imaging studies to examine activity in the human hippocampus during sleep (Higgins & George, 2013; Maquet et al., 1996). Maquet and his colleagues taught new tasks to the study participants and had them sleep while monitoring brain activity. The next day, though all participants showed improvement in task completion, those who had the greatest hippocampal activity during slow wave sleep showed the greatest improvement in task completion (Higgins & George, 2013).

More recently Staresina et al. used intracranial electroenphalogram recordings from epileptic patients to test multi-stage hypothesis of memory storage during sleep. Based on their findings the researchers concluded that memory formation occurs in a two-step process. First our memories exist as mnemonic representations in the medial temporal lobe of our hippocampus. Secondly, during consolidation these representations move to more permanent storage (Staresina et al., 2015). The researchers concluded that non-rapid eye movement sleep facilitates consolidation of memories, especially declarative, hippocampal-dependent, thought content (Staresina et al., 2015).

After exploring how memory consolidation occurs during sleep, I next wondered: what happens when what we are experiencing is not something we want to remember? How does sleep-dependent memory consolidation following a traumatic experience impact the development of psychiatric disorders such as PTSD? Memories of past traumas can become intrusive and have a debilitating impact on everyday functioning. They say the best intervention is prevention. So, what if there was an early intervention for people who had experienced trauma? Could it preclude the need for, or be used in conjunction with, therapy and other conventional modes of treatment by preventing the formation of intrusive and debilitating memories? And, what if that intervention were a notorious practice that has become synonymous with inhumane torture practices?

The counterintuitive concept of the benefits of sleep deprivation following a traumatic experience has been discussed in literature. Surprisingly, however, it had never been studied until this past year. Researchers at Oxford University designed and carried out a study to assess the potential of inhibiting the process of memory formation through sleep deprivation immediately following exposure to an emotionally charged, potentially traumatic, event (Porcheret, Holmes, Goodwin, Foster & Wulff, 2015). Using a sample of 42 healthy students ages 18-25 with no prior mental or physical health issues, including sleep disturbances, Porcheret et al. put the concept of sleep deprivation as treatment to the test. The researchers used an analogue of witnessing a traumatic event, known as the trauma film paradigm. The trauma film paradigm involves participants watching a film with disturbing content. Prior to this, the content has been clinically shown to elicit a stress response (measured through skin conductance and heart rate), alter mood, and induce intrusive memories (Porcheret et al., 2015). All participants watched the video and while the sleep group was allowed to sleep immediately following watching the film the non-sleep group was kept awake for 24 hours.

Using the Impact of Event Scale-Revised (IES-R), a 22-question scale that assesses aspects of PTSD symptomatology, Porcheret et al. found that one day following watching the film the sleep deprived group had a significantly lower mean score (m=8.47, SD=5.31) as compared to the sleep group (m=11.52, SD=6.64). During the week following viewing of the film the sleep-deprived group reported significantly less intrusive memories (m=2.28, SD=2.91), than the sleep group (mean=3.76, SD=3.35) (Porcheret et al., 2015). These results indicate the possibility that sleep deprivation may be beneficial following exposure to a negative or upsetting event.

This study is important because it compels us to consider whether sleep deprivation, once considered universally inhumane and an instrument of torture, may one day be employed as a strategy to reduce the saliency of emotionally charged, traumatic memories. This study has clear limitations and at this time is not generalizable to PTSD. Despite this, the results were surprising and the concept is worthy of further consideration from researches and ethicists alike.

 

References:

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

Goerke, M., Müller, N., & Cohrs, S. (2015). Sleep-dependent memory consolidation and its implications for psychiatry. Journal of Neural Transmission. doi:10.1007/s00702-015-1476-3

Higgins, E., & George, M. (2013). Chapter 15: Sleep and Circadian Rhythms. In Neuroscience of clinical psychiatry: The pathophysiology of behavior and mental illness (Second ed., pp. 175-186). Philadelphia, PA: Lipincott Williams & Wilkins.

Maquet, P., Péters, J., Aerts, J., Delfiore, G., Degueldre, C., Luxen, A., & Franck, G. (1996). Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature, 383, 163-166. doi:10.1038/383163a0

Porcheret, K., Holmes, E., Goodwin, G., Foster, R., & Wulff, K. (2015). Psychological Effect of an Analogue Traumatic Event Reduced by Sleep Deprivation. Sleep, 38(7) 2015, 1017-1025. DOI: 10.5665/sleep.4802

Staresina, B., Bergmann, T., Bonnefond, M., Meij, R., Jensen, O., Deuker, L., Elger, E., Axmacher, N., Fell, J. (2015). Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep. Nature Neuroscience Nat Neurosci, 1679-1686. doi:10.1038/nn.4119

Uppsala University. (2015, July 13). Losing half a night of sleep makes memories less accessible in stressful situations. ScienceDaily. Retrieved October 20, 2015 from www.sciencedaily.com/releases/2015/07/150713150822.htm

University of Exeter. (2015, July 26). Sleep makes our memories more accessible, study shows. ScienceDaily. Retrieved November 5, 2015 from www.sciencedaily.com/releases/2015/07/150726200036.htm

Wagner, U., Gais, S., & Born, J. (2001). Emotional memory formation is enhanced across sleep intervals with high amounts of rapid eye movement sleep. Learning & Memory, 8(2), 112-119.

Xie, M., Yan, J., He, C., Yang, L., Tan, G., Li, C., . . . Wang, J. (2015). Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus. Behavioural Brain Research, 286, 64-70. doi:10.1016/j.bbr.2015.02.040

 

 

Understanding Postpartum Depression

The period following the birth of a child is an exciting and emotional time for new parents.  It is not uncommon for new mothers to experience a period of “baby blues” in the first few weeks following delivery.  This occurs in 50% to 80% of women after giving birth and is characterized by relatively mild and temporary symptoms of depressed mood, irritability, sleep or appetite disturbances, anxiety, and crying.  The symptoms typically present within the few days after delivery and generally do not last longer than two weeks (Bobo & Yawn, 2014).

In comparison, postpartum depression (PPD) is a disorder characterized by more intense and persistent symptoms of depression.  These symptoms may include depressed mood, sleep disturbances, changes in appetite or weight, feelings of worthlessness, fatigue, difficulty concentrating, loss of pleasure or interest in activities, psychomotor agitation or retardation, and suicidal ideations (Bobo & Yawn, 2014).  PPD has been estimated to occur in up to 20% of postpartum women (Werner, Miller, Osborne, Kuzava, & Monk, 2015).  The onset of symptoms occurs most often between 10 and 19 days postpartum (Frokjaer, 2015).  PPD is most prevalent between the second and sixth months postpartum.  The symptoms remain for at least seven months following delivery in 25% to 50% of women and may persist for over a year (Bobo & Yawn, 2014).

Not only does PPD seriously affect the well-being of the mother, it can have detrimental to the health of the family.  PPD in mothers can lead to impaired mother-infant interactions and disrupt infant attachment.  It is associated with many negative outcomes in infants including failure-to-thrive, impaired social and cognitive development, and future mental health problems (Frokjaer, 2015; Pinsonneault et al., 2013).

There are many known risk factors for PPD.  These risk factors include low social class, acute chronic stressors during the perinatal period, complications with pregnancy or birth, inadequate support from others, prior history of mood disorders or sexual abuse, poor relationships with the mother’s partner or with her own mother, bottle feeding, and depression during pregnancy (Werner, Miller, Osborne, Kuzava, & Monk, 2015).  O’Hara and Wisner (2014) suggest that the risk factors are comprised of three major constellations:  “history of psychiatric illness, which may range from mild to severe, life stress, and poor social relationships” (p. 9).  There are multiple hypotheses of the etiology of PDD.  However, the exact cause of PPD is not well understood and there are likely multiple factors that contribute to its development (Bobo & Yawn, 2014).

The large fluctuation in hormone levels during the perinatal period is often hypothesized as a significant contributor to the development of “baby blues” as well as PPD.  Women experience significantly higher than normal levels of steroid hormones including estradiol and progesterone during pregnancy.  These levels are particularly elevated during the last weeks before birth and decline rapidly in the first days after delivery (Brummelte & Galea, 2015).

Interestingly, low estradiol levels are associated with increased activity of monoamine oxidase in the brain.  Monoamine oxidase is a type of enzyme that contributes to the breakdown of certain neurotransmitters including serotonin, dopamine, and norepinephrine.  These neurotransmitters are believed to be important in mood regulation.  Monoamine oxidase inhibitors are a group of antidepressant medications that inhibit the activity of monoamine oxidase, leading to an increase in levels of these neurotransmitters.  Monoamine oxidase levels in women have been found to be 43% higher four to six days postpartum, indicating that these neurotransmitters are more quickly broken down during a time that coincides with the onset of “baby blues” and PPD (O’Hara & Wisner, 2014).

Results from a study conducted by Bloch et al. (2000) highlight the role hormone fluctuations may play in the development of PPD.  The study included 16 healthy, euthymic women.  Half of the women had history of PPD while the other half had given birth one or more times but had no prior history of PPD.  The women were administered treatments to achieve supraphysiological levels of estradiol and progesterone during an eight week period.  The estradiol and progesterone were then withdrawn in a double-blind manner to simulate conditions of normal perinatal hormone fluctuations.  Five of the eight women with a history of PPD experienced significant mood changes and depressive symptoms during the withdrawal period, while none of the other eight participants developed these symptoms.  The results suggest that, for some reason, women who experience PPD may be more susceptible to the postpartum rapid decline in progesterone and estradiol levels than other women.

In another study, Maguire and Mody (2008) sought to understand why certain women may be more susceptible to depression symptoms related to fluctuations in hormone levels.  It was hypothesized that the delta subunit of the GABAA receptor may play a role in PPD.  Researchers examined behaviors in two groups of mice during the postpartum period, wild-type mice and mice that were genetically altered to have a reduced number of delta subunits of the GABAA receptors.  The genetically altered mice were found to display signs of PPD including lack of pleasure-seeking behaviors (not seeking sucrose-water over plain water), inactivity, and neglect of their offspring.  When these mice were administered THIP (a drug intended to restore the normal function of the GABAA receptors) the depression-like behaviors were reversed.  Of course further research is needed to better understand this process and how it relates to human mothers but these findings do present an exciting target of research for the development of new therapeutic interventions to treat PPD.

The role that hormones may play in the development of PPD was briefly discussed in this blog post.  This seems to be an important part of understanding PPD.  However, the etiology of PPD is likely far more complex with many other factors contributing to its development.

 

References

Bloch, M., Schmidt, P. J., Danaceau, M., Murphy, J., Nieman, L., & Rubinow, D. R. (2000). Effects of gonadal steroids in women with a history of postpartum depression. American Journal of Psychiatry, 157(6), 924-930.

Bobo, W. V., & Yawn, B. P. (2014). Concise review for physicians and other clinicians: Postpartum depression. Mayo Clinic Proceedings, 89(6), 835-844.

Brummelte, S., & Galea, L. A. (2015). Postpartum depression: Etiology, treatment and consequences for maternal care. Hormones and Behavior.

Frokjaer, V. G., Pinborg, A., Holst, K. K., Overgaard, A., Henningsson, S., Heede, M., … & Knudsen, G. M. (2015). Role of serotonin transporter changes in depressive responses to sex-steroid hormone manipulation: A positron emission tomography study. Biological Psychiatry, 78(8), 534-543.

Maguire, J., & Mody, I. (2008). GABAA R plasticity during pregnancy: Relevance to postpartum depression. Neuron59(2), 207-213.

O’Hara, M. W., & Wisner, K. L. (2014). Perinatal mental illness: Definition, description and aetiology. Best Practice & Research Clinical Obstetrics & Gynaecology28(1), 3-12.

Pinsonneault, J. K., Sullivan, D., Sadee, W., Soares, C. N., Hampson, E., & Steiner, M. (2013). Association study of the estrogen receptor gene ESR1 with postpartum depression: A pilot study. Archives of Women’s Mental Health, 16(6), 499-509.

Werner, E., Miller, M., Osborne, L. M., Kuzava, S., & Monk, C. (2015). Preventing postpartum depression: Review and recommendations. Archives of Women’s Mental Health18(1), 41-60.